OBJECTIVE To establish population pharmacokinetic model of levetiracetam （Lev） for Chinese patients with post- stroke epilepsy （PSE）， and provide reference for formulating individualized dosing regimens for Lev therapy in this specific population. METHODS Blood concentration data and clinical diagnosis and treatment information of PSE patients meeting the inclusion criteria were retrospectively collected and divided into model group and validation group at an 8∶2 ratio using a random number method. Based on the model group data， a population pharmacokinetic model was developed using nonlinear mixed-effects modeling. Internal evaluation was performed through goodness-of-fit tests and bootstrap analysis， while external validation was conducted using the validation group data. RESULTS A total of 75 blood concentration measurements from 70 PSE patients were collected， with 60 measurements from 55 patients used for model development and 15 measurements from 15 patients reserved for external validation. The final model estimated a population typical value of clearance at 2.98 L/h. Estimated glomerular filtration rate， daily dose， and homocysteine level significantly influenced clearance of Lev （P＜0.01）. The model demonstrated satisfactory predictive performance， as evidenced by goodness-of-fit tests， bootstrap analysis， and external validation results. CONCLUSIONS Daily dose， estimated glomerular filtration rate， and homocysteine level are identified as significant covariates influencing Lev clearance in Chinese PSE patients. When making clinical decisions， comprehensive consideration should be given to the patient’s treatment response， physiological and pathological conditions， and the occurrence of adverse reactions， etc. The dosage of Lev should be adjusted based on the results of population pharmacokinetic model.

Objective:To explore the risk factors of postpartum hemorrhage in parturients undergoing vaginal delivery with a second child and establish a risk prediction model.Methods:Using the convenient sampling method, a total of 2 500 parturients undergoing vaginal delivery with a second child who underwent regular prenatal examinations at Peking University Third Hospital from July 2019 to March 2023 were selected as the research objects. According to the amount of blood loss, parturients with blood loss greater than or equal to 500 ml within 24 hours after delivery were selected as the case group ( n=278), while parturients with blood loss less than 500 ml within 24 hours after delivery in the same period were selected as the control group ( n=2 222). Univariate analysis and binomial Logistic regression were used to analyze the influencing factors of postpartum hemorrhage in parturients with vaginal delivery with a second child. Based on the selected risk factors, a nomogram prediction model was established using R software, and the consistency of the model was tested. Results:The incidence of postpartum hemorrhage in 2 500 parturients undergoing vaginal delivery with a second child was 11.12% (278/2 500). Binomial Logistic regression analysis showed that in in vitro fertilization-embryo transfer, pre-delivery body mass index, lateral perineal incision, neonatal weight, placenta previa, placenta implantation and manual extraction of placenta were the influencing factors for postpartum hemorrhage in parturients undergoing vaginal delivery with a second child ( P<0.05). According to the influencing factors, a nomogram model was established to predict the probability of postpartum hemorrhage in women who gave birth to a second child. The C- index of the prediction model was 0.706, the area under the receiver operating characteristic curve was 0.706, and the χ 2 value of the Hosmer-Lemeshow goodness-of-fit test was 7.720 ( P=0.461) . Conclusions:In vitro fertilization embryo transfer, pre-delivery body mass index, perineal lateral resection, neonatal weight, placenta previa, placental implantation and manual extraction of placenta are risk factors for postpartum hemorrhage in parturients undergoing vaginal delivery for a second child. The prediction model constructed based on risk factors has certain accuracy and clinical value for predicting postpartum hemorrhage in parturients with vaginal delivery of a second child.

Objective:To summarize the best evidence of medication adherence interventions for patients with multiple chronic conditions.Methods:According to the "6S" evidence model, literature on medication adherence in patients with multiple chronic conditions was retrieved from BMJ Best Clinical Practice, UpToDate, Medlive, National Institute for Health and Clinical Excellence, Cochrane Library, Embase, PubMed, Web of Science, China Biology Medicine disc, China National Knowledge Infrastructure, WanFang data and so on. The search period was from establishing the database to August 30, 2023.Results:A total of 16 articles were included, including three guidelines, four expert consensus, seven systematic reviews, and two meta-analyses. Twenty-seven pieces of evidence were summarized from six aspects of compliance assessment, educational intervention, behavioral intervention, optimized treatment program, technical reminder intervention, and social-psychological-emotional intervention.Conclusions:The best evidence of medication adherence interventions for patients with multiple chronic conditions summarized provides a reference for medical and nursing staff to develop medication adherence interventions.

Immunotherapy has made breakthrough in the field of tumor treatment. How to accurately predict the response of tumor patients to immunotherapy in the early stage is currently a clinical challenge. Nuclear medicine molecular imaging provides a new technological means for early accurate diagnosis, treatment monitoring, early warning of recurrence and metastasis, and guidance for personalized treatment of diseases. Therefore, it plays an irreplaceable role in precise diagnosis and treatment of tumors and patient stratification. This article reviews the progress of molecular imaging research on immune cells and related targets within the tumor microenvironment.

Objective:To develop a risk prediction model of acute cerebral infarction (ACI) in patients with type 2 diabetes mellitus (T2DM).Methods:It was a cross-sectional study. The clinical data of 798 patients with T2DM hospitalized in the Department of Endocrinology and Neurology of Shanxi Bethune Hospital from August 2021 to October 2023 were collected. Based on whether they had concurrent ACI, the patients were divided into T2DM with ACI group (case group) and pure T2DM group (control group). The patients were then allocated to a training set ( n=558) and a validation set ( n=240) in a 7∶3 ratio by the sample functions in R software. LASSO regression was employed to screen and optimize variables, and a multivariate logistic regression analysis was used to establish the nomogram prediction model. The discriminative ability, calibration, and clinical usefulness of the risk prediction model were assessed with receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis, respectively. Results:LASSO regression identified gender, age, systolic blood pressure, fasting plasma glucose (FPG), albumin (ALB), and carotid vascular condition as the variables for prediction. The multivariable logistic regression analysis showed that female ( OR=0.489, 95% CI: 0.308-0.778) and ALB ( OR=0.846, 95% CI: 0.795-0.901) were protective factors for ACI occurrence in T2DM patients, while age ( OR=1.051, 95% CI:1.025-1.077), systolic blood pressure ( OR=1.047, 95% CI: 1.034-1.059), FPG ( OR=1.185, 95% CI: 1.089-1.288), and carotid plaque ( OR=7.359, 95% CI: 3.050-17.756) were risk factors. The area under the ROC curve (AUC) for risk of ACI in the training set was 0.863(95% CI: 0.833-0.893), and it was 0.846(95% CI: 0.797-0.896) for the validation set. Calibration curves and the Hosmer-Lemeshow goodness-of-fit test indicated good model fit (training set χ2=8.311, P=0.404; validation set χ2=3.957, P=0.861). Decision curve analysis showed that the clinical effectiveness of the model was higher when the threshold probabilities of the training set and the validation set was 0.02-0.93 and 0.12-0.99, respectively. Conclusion:In this study, a prediction model of ACI risk in T2DM patients was successfully established.

Objective:To study the role of special microbial communities in the development of periodontitis in type 2 diabetes melli-tus(T2DM)patients.Methods:40 subjects aged 20-70 years were included and divided into 3 groups:moderate to severe periodon-titis with T2DM(SP.T2DM,n=15),moderate to severe periodontitis group(SP,n=15)and normal healthy group(N,n=10).The basic information,periodontal clinical indicators and blood sugar of the subjects were recorded.Subgingival plaque samples were col-lected,DNA samples of the plaque were extracted,and sequenced by Illumina NovaSeq6000 platform.The microbial diversity,eco-logical characteristics and functions of the plaque were analyzed by Uparse,SPSS and other softwares.Results:481 species in 22 phyla,30 classes,73 orders,129 families and 265 genera were obtained from the samples.Beta polymorphism analysis showed that the species composition of CP.T2DM group and CP group was similar.Alpha polymorphism analysis showed that the species richness and evenness in CP.T2DM group and CP group were higher than those in N group(P＜0.01).Venn diagram analysis showed that the species richness of the plaque in CP.T2DM group was the highest,followed by CP group and the lowest in N group.At the genus lev-el,Klebsiella and Bifidobacterium in CP.T2DM group were larger than those in CP group and N group(P＜0.05),and between group CP and N,P＞0.05.At the species level,the Capnocytophaga leadbetteri in CP.T2DM group was higher than that in CP group and N group(P＜0.05),between group CP and N,P＞0.05;There were some differences in the microbial community structure of subgingival plaque among the 3 groups.The species richness of subgingival flora in patients with CP and T2DM was higher than that in patients with CP and healthy people.Conclusion:The increase of Klebsiella,Bifidobacterium and Capnocytophaga leadbetter in subgingival flora of patients with moderate and severe periodontitis may be related to the development of T2DM.

Objective:To study the epidemiological characteristics of brucellosis (hereinafter referred to as brucellosis) among non-occupational population in Jinan City, and to provide a basis for formulating further prevention and control measures.Methods:From "the Infectious Disease Monitoring System of the China Center for Disease Control and Prevention", Center for Disease Control and Prevention of Jinan City and its subordinate counties, the epidemiological data and case investigation data of brucellosis in Jinan from 2012 to 2021 were collected and statistically analyzed using descriptive epidemiological methods.Results:From 2012 to 2021, a total of 453 cases of brucellosis were reported in the non-occupational population of Jinan City, accounting for 20.21% (453/2 241) of the total number of cases. The proportion of brucellosis cases in the non-occupational population showed an increasing trend year by year (χ 2tend = 25.50, P < 0.001). Among the non-occupational population, there were 317 males and 136 females, with a gender ratio of 2.33∶1.00; the age was (46.34 ± 17.72) years old, with a minimum age of 1 year and a maximum age of 86 years. The majority of the affected population were farmers, accounting for 71.74% (325/453). The peak onset time was April and May. The main routes of infection were through the digestive tract and respiratory tract, accounting for 36.87% (167/453) and 33.77% (153/453), respectively. The clinical symptoms were mainly fever, muscle soreness, fatigue, and hyperhidrosis. The diagnosis time was 20.0 (7.5, 37.5) d, and the sensitivity of city and district general hospitals to detect and diagnose brucellosis was relatively low. Conclusions:The incidence rate of brucellosis among non-occupational population in Jinan is increasing year by year. The high incidence season is spring, and the high incidence population is male young and middle-aged farmers. Digestive and respiratory transmission are the main transmission routes, with atypical clinical symptoms and a long diagnosis time. The next step is to strengthen the promotion of brucellosis prevention and control knowledge and the training of medical personnel in brucellosis diagnosis.

Objective To investigate the effects of Danshen Tongluo Jiedu Decoction medicated serum for regulating miR-126 on autophagy in hypoxia/reoxygenation myocardial microvascular endothelial cells(CMECs)of rats.Methods Hypoxia/reoxygenation injury cell model was constructed by culturing CMECs in vitro.The cells were divided into blank group,model group,TCM group,silencing group,empty vector group,and silencing+TCM group by lentivirus transfection with miR-126 inhibitor.Lactate dehydrogenase(LDH)content in the supernatant of CMECs was detected using a reagent kit,and cell apoptosis rate was detected using flow cytometry,the miR-126 mRNA expression was detected using RT-PCR,the expressions of autophagy-related proteins Atg5,Beclin1 and p62 proteins were detected by Western blot.Results Compared with the blank group,the LDH content in the supernatant of the model group cells significantly increased,the apoptosis rate significantly increased,the miR-126 mRNA expression significantly decreased,the Atg5 and Beclin1 protein expressions significantly increased,and the p62 protein expression significantly decreased,with statistical significance(P<0.01).Compared with the model group,the TCM group and the silencing+TCM group showed a significant decrease in LDH content in the cell supernatant,a significant decrease in cell apoptosis rate,a significant increase in miR-126 mRNA expression,a significant decrease in Atg5 and Beclin1 protein expressions,and a significant increase in p62 protein expression in the TCM group,with statistical significance(P<0.05,P<0.01);the LDH content in the supernatant,apoptosis rate,Atg5 and Beclin1 protein expressions of the silence group cells significantly increased,while miR-126 mRNA expression significantly decreased(P<0.01).Compared with the TCM group,the LDH content in the cell supernatant and apoptosis rate of the silence group and the silencing+TCM group significantly increased(P<0.05,P<0.01),while the miR-126 mRNA expression significantly decreased(P<0.01);the expressions of Atg5 and Beclin1 proteins in the silence group significantly increased(P<0.01),and the expression of p62 protein significantly decreased(P<0.01).Compared with the silence group,the LDH content in the cell supernatant,apoptosis rate,and Atg5 and Beclin1 protein expression of the empty vector group group and the silencing+TCM group were significantly decreased(P<0.01),the miR-126 mRNA and p62 protein expression significantly increased(P<0.05,P<0.01).Conclusion Danshen Tongluo Jiedu Decoction medicated serum can inhibit autophagy and apoptosis of CMECs caused by hypoxia/reoxygenation injury,thereby protecting CMECs.Its mechanism may be related to promoting miR-126 expression.

Objective: To systematically evaluate the influencing factors for medication compliance in patients with comorbidities of chronic diseases, so as to provide the evidence for improving medication compliance. Methods: Literature on influencing factors for medication compliance in patients with comorbidities of chronic diseases were retrived from CNKI, Wanfang Data, VIP, SinoMed, PubMed, Web of Science, Cochrane Library and Embase from inception to January 20, 2024. After independent literature screening, data extraction, and quality assessment by two researchers, a meta-analysis was performed using RevMan 5.4 and Stata 16.0 softwares. Literature were excluded one by one for sensitivity analysis. Publication bias was assessed using Egger's test. Results: Initially, 7 365 relevant articles were retrieved, and 35 of them were finally included, with a total sample size of about 150 000 individuals. There were 30 cross-sectional studies and 5 cohort studies; and 11 high-quality studies and 24 medium-quality studies. The meta-analysis showed that the demographic factors of lower level of education (OR=2.148, 95%CI: 1.711-2.696), lower economic income (OR=1.897, 95%CI: 1.589-2.264), male (OR=0.877, 95%CI: 0.782-0.985), living alone (OR=2.833, 95%CI: 1.756-4.569) and unmarried (OR=2.784, 95%CI: 1.251-6.196); the medication treatment factors of polypharmacy (OR=1.794, 95%CI: 1.190-2.706), potentially inappropriate medication (OR=2.988, 95%CI: 1.527-5.847), low frequency of daily medication (OR=0.533, 95%CI: 0.376-0.754) and adverse drug reactions (OR=3.319, 95%CI: 1.967-5.602); the disease factors of long course of disease (OR=2.118, 95%CI: 1.643-2.730), more comorbidities (OR=1.667, 95%CI: 1.143-2.431) and cognitive impairment (OR=2.007, 95%CI: 1.401-2.874); and the psychosocial factors of poor belief in taking medication (OR=1.251, 95%CI: 1.011-1.547), poor self-rated health (OR=1.990, 95%CI: 1.571-2.522) and being guided by healthcare professionals (OR=0.151, 95%CI: 0.062-0.368) were the influencing factors for medication compliance in patients with chronic comorbidities. Conclusion The medication compliance in patients with comorbidities of chronic diseases is associated with demographic factors, pharmacological factors, disease factors and psychosocial factors, mainly including living alone, adverse drug reactions, course of disease, number of comorbidities and medication beliefs.

Objective To study the effect of changes in estradiol(E2)levels on the reproductive outcomes of pa-tients with polycystic ovary syndrome(PCOS)undergoing controlled ovarian stimulation(COS)with gonadotropin-releasing hormone antagonist(GnRH-ant)protocol.Methods A retrospective study was conducted involving 338 patients with polycystic ovary syndrome(PCOS)infertility who underwent GnRH-ant protocol for controlled ovarian hyperstimulation followed by in vitro fertilization(IVF)or intracytoplasmic sperm injection(ICSI),and subse-quently underwent their first frozen-thawed embryo transfer(FET).The clinical data of these patients were ana-lyzed.Patients were grouped based on the changes in serum E2 levels on the first and fourth day of GnRH-ant ad-ministration(blood samples collected before GnRH-ant injection):the E2 elevation group(Group A,E2 value in-creased more than 30％,165 cases),the E2 stable group(Group B,E2 rate of change was within-30％～30％,162 cases),and the E2 decline group(E2 value declined more than 30％,11 cases,not included in statistical a-nalysis due to small sample size).The differences in demographic characteristics,ovulation induction outcomes,embryo outcomes and clinical pregnancy-related indicators were analyzed between Groups A and B.Results There were no statistically significant differences in basic information such as age,duration of infertility,body mass index(BMI),basal endocrine levels,and anti-Müllerian hormone(AMH)levels between groups A and B.Regarding embryo characteristics,there were no statistically significant differences in fertilization method and number of trans-ferred embryos between groups A and B.However,group A had a higher total number of retrieved oocytes,normal fertilization rate,number of high-quality embryos,and rate of high-quality embryos compared to group B,with sta-tistically significant differences(P＜0.05).In terms of clinical pregnancy outcomes,there were no statistically significant differences in the incidence of severe ovarian hyperstimulation syndrome(OHSS)between groups A and B.However,group A had higher rates of clinical pregnancy,implantation,and live birth compared to group B,with statistically significant differences.Group A also had a lower rate of early miscarriage compared to group B,with statistically significant differences.Conclusion Choosing the GnRH-ant protocol for IVF/ICSI-FET in PCOS patients,if the blood E2 level increases by more than 30％after 4 days of adding the antagonist(blood sample col-lected before administering GnRH-ant),the clinical pregnancy outcome will be better.