OBJECTIVE To systematically analyze the population pharmacokinetics （PPK） studies of lacosamide and expound the influential factors of its pharmacokinetics in different populations. METHODS PPK studies of lacosamide were collected by searching the databases， such as Web of Science， PubMed， Embase， Metasearch， CNKI， Wanfang Data and VIP， both in Chinese and English. Relevant data were extracted， and the Prediction Model Risk of Bias Assessment Tool was used to evaluate the quality of the PPK models in the included studies. RESULTS Among 8 studies ultimately included， 6 were retrospective studies and 2 were prospective studies； 5 studies involved pediatric patients. Seven studies adopted a one-compartment model， while 1 study utilized a two-compartment model. Four studies had a model quality rating of grade A， two of grade B and two of grade C， respectively. Body weight， renal function， and hepatic enzyme inducers were significant covariates influencing PPK of lacosamide. CONCLUSIONS The existing PPK studies of lacosamide are predominantly conducted in pediatric populations. Pharmacokinetic variability is mainly influenced by body weight， renal function， and hepatic enzyme inducers. However， most PPK studies have not conducted external validation， and the generalizability of the models remains to be confirmed.

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 observe the effects of Yixintai on lipid metabolism and the protein expressions of CPT-1 and CD36 in rats with heart failure;To explore the mechanism of its treatment of heart failure.Methods 106 out of 120 SD rats were selected to establish the heart failure model induced by myocardial infarction by ligating the left anterior descending coronary artery,and 14 rats were selected as the sham-operation group.The successful model rats were randomly divided into model group,trimetazidine group and Yixintai low-,medium-and high-dosage groups,with 14 rats in each group.The administration group was given corresponding drugs by gavage once a day for 4 weeks.LVEF,LVFS,LVIDd and LVIDs were measured by color doppler ultrasonography,the contents of ANP,BNP,LA and FFA in serum were detected by ELISA,the contents of TG,TC,LDL and HDL were detected by automatic biochemical analyzer,HE and Masson staining were used to observe the morphology of myocardial tissue,the expressions of CPT-1 and CD36 protein in myocardial tissue were detected by Western blot.Results Compared with the sham-operation group,LVEF and LVFS in the model group decreased(P<0.05),the LVIDs and LVIDd increased(P<0.05);the contents of serum ANP,BNP,LA,FFA,TG,TC and LDL increased(P<0.05),while the content of HDL decreased(P<0.05),with myocardial edema,irregular arrangement of myocardial fibers,increased inflammatory cell infiltration and collagen fiber deposition;the protein expressions of CPT-1 and CD36 in myocardial tissue decreased(P<0.05).Compared with the model group,the LVEF and LVFS in Yixintai each dosage groups and trimetazidine group increased(P<0.05),LVIDs and LVIDd decreased(P<0.05);the contents of ANP,BNP,LA,FFA,TG,TC and LDL in serum of Yixintai medium-and high-dosage groups and trimetazidine group decreased(P<0.05),the content of HDL increased(P<0.05);myocardial edema was improved,inflammatory cell infiltration was reduced,collagen fiber deposition was reduced,and the protein expressions of CPT-1 and CD36 in myocardial tissue increased(P<0.05).Conclusion Yixintai may improve myocardial energy metabolism and treat heart failure by increasing the expression of CPT-1 and CD36 protein in myocardial tissue and promoting fatty acid β oxidation.

Objective:To explore the level of positive psychological capital and its trends in traumatic lower limb amputation patients during the 15 months after surgery, and to identify the time period when the patients' level of positive psychological capital is weak, so as to provide a basis for interventions.Methods:This study was a prospective longitudinal study. Convenience sampling was used to select 143 patients with traumatic lower limb amputation admitted to the Department of Emergency Medicine of the First Affiliated Hospital of Zhengzhou University from January 2021 to November 2022 for the study. General information questionnaire, Positive Psychological-Capital Questionnaire (PPQ) were used on the third postoperative day (T1) , on the day of discharge (T2) , 1 month (T3) , 2 months (T4) , 3 months (T5) , 6 months (T6) , 9 months (T7) , 12 months (T8) , and 15 months (T9) after discharge for a total of nine time points to administer the questionnaire to the patients. One-way repeated-measures ANOVA and plotting of results were performed on the nine time-point data using Graph Pad prism 9.5 software and SPSS 21.0 software, and the data were compared two-by-two using the Bonferroni multiple comparison test.Results:There were 143, 139, 132, 129, 122, 120, 119, 118, and 116 patients who participated in the survey from T1 to T9 time points, with a loss to follow-up rate of 18.88% (27/143) . PPQ scores of 116 traumatic lower limb amputation patients at nine time points were (103.25±9.03) , (108.53±9.32) , (104.38±9.60) , (99.71±9.61) , (95.82±9.55) , (91.49±9.41) , (93.34±9.29) , (93.53±9.14) , (93.62±9.05) , and the mean PPQ scores were lower than the theoretical mean (104) at all time points except T2 and T3 time points. One-way repeated-measures ANOVA showed that the difference in the change in the level of positive psychological capital of patients after traumatic lower limb amputation from postoperative day 3 to 15 months after discharge was statistically significant ( F=990.144, P<0.01) . Bonferroni's multiple comparison test showed that there was no statistically significant difference in two-by-two comparisons between T7, T8, and T9 time points with each other ( P>0.05) , and the rest of the two-by-two comparisons were statistically significant ( P<0.05) . Changes in the total PPQ score and the curves of the self-efficacy dimension, resilience dimension, hope dimension, and optimism dimension scores all showed a trend of a brief increase, followed by a continuous decrease, and then a slow increase to a plateau. Conclusions:Traumatic lower limb amputation patients show a wide range of changes in positive psychological capital levels from postoperative day 3 to 15 months after discharge, with a trend of a brief increase at discharge, followed by a steady decline, and then a slow increase to a plateau. Healthcare professionals should pay dynamic attention to the psychological state and psychological strength of patients after traumatic lower limb amputation and provide targeted interventions at different stages after discharge.

Objective:To explore the level of positive psychological capital and its trends in traumatic lower limb amputation patients during the 15 months after surgery, and to identify the time period when the patients' level of positive psychological capital is weak, so as to provide a basis for interventions.Methods:This study was a prospective longitudinal study. Convenience sampling was used to select 143 patients with traumatic lower limb amputation admitted to the Department of Emergency Medicine of the First Affiliated Hospital of Zhengzhou University from January 2021 to November 2022 for the study. General information questionnaire, Positive Psychological-Capital Questionnaire (PPQ) were used on the third postoperative day (T1) , on the day of discharge (T2) , 1 month (T3) , 2 months (T4) , 3 months (T5) , 6 months (T6) , 9 months (T7) , 12 months (T8) , and 15 months (T9) after discharge for a total of nine time points to administer the questionnaire to the patients. One-way repeated-measures ANOVA and plotting of results were performed on the nine time-point data using Graph Pad prism 9.5 software and SPSS 21.0 software, and the data were compared two-by-two using the Bonferroni multiple comparison test.Results:There were 143, 139, 132, 129, 122, 120, 119, 118, and 116 patients who participated in the survey from T1 to T9 time points, with a loss to follow-up rate of 18.88% (27/143) . PPQ scores of 116 traumatic lower limb amputation patients at nine time points were (103.25±9.03) , (108.53±9.32) , (104.38±9.60) , (99.71±9.61) , (95.82±9.55) , (91.49±9.41) , (93.34±9.29) , (93.53±9.14) , (93.62±9.05) , and the mean PPQ scores were lower than the theoretical mean (104) at all time points except T2 and T3 time points. One-way repeated-measures ANOVA showed that the difference in the change in the level of positive psychological capital of patients after traumatic lower limb amputation from postoperative day 3 to 15 months after discharge was statistically significant ( F=990.144, P<0.01) . Bonferroni's multiple comparison test showed that there was no statistically significant difference in two-by-two comparisons between T7, T8, and T9 time points with each other ( P>0.05) , and the rest of the two-by-two comparisons were statistically significant ( P<0.05) . Changes in the total PPQ score and the curves of the self-efficacy dimension, resilience dimension, hope dimension, and optimism dimension scores all showed a trend of a brief increase, followed by a continuous decrease, and then a slow increase to a plateau. Conclusions:Traumatic lower limb amputation patients show a wide range of changes in positive psychological capital levels from postoperative day 3 to 15 months after discharge, with a trend of a brief increase at discharge, followed by a steady decline, and then a slow increase to a plateau. Healthcare professionals should pay dynamic attention to the psychological state and psychological strength of patients after traumatic lower limb amputation and provide targeted interventions at different stages after discharge.

Objective To observe the effects of Yixintai on lipid metabolism and the protein expressions of CPT-1 and CD36 in rats with heart failure;To explore the mechanism of its treatment of heart failure.Methods 106 out of 120 SD rats were selected to establish the heart failure model induced by myocardial infarction by ligating the left anterior descending coronary artery,and 14 rats were selected as the sham-operation group.The successful model rats were randomly divided into model group,trimetazidine group and Yixintai low-,medium-and high-dosage groups,with 14 rats in each group.The administration group was given corresponding drugs by gavage once a day for 4 weeks.LVEF,LVFS,LVIDd and LVIDs were measured by color doppler ultrasonography,the contents of ANP,BNP,LA and FFA in serum were detected by ELISA,the contents of TG,TC,LDL and HDL were detected by automatic biochemical analyzer,HE and Masson staining were used to observe the morphology of myocardial tissue,the expressions of CPT-1 and CD36 protein in myocardial tissue were detected by Western blot.Results Compared with the sham-operation group,LVEF and LVFS in the model group decreased(P<0.05),the LVIDs and LVIDd increased(P<0.05);the contents of serum ANP,BNP,LA,FFA,TG,TC and LDL increased(P<0.05),while the content of HDL decreased(P<0.05),with myocardial edema,irregular arrangement of myocardial fibers,increased inflammatory cell infiltration and collagen fiber deposition;the protein expressions of CPT-1 and CD36 in myocardial tissue decreased(P<0.05).Compared with the model group,the LVEF and LVFS in Yixintai each dosage groups and trimetazidine group increased(P<0.05),LVIDs and LVIDd decreased(P<0.05);the contents of ANP,BNP,LA,FFA,TG,TC and LDL in serum of Yixintai medium-and high-dosage groups and trimetazidine group decreased(P<0.05),the content of HDL increased(P<0.05);myocardial edema was improved,inflammatory cell infiltration was reduced,collagen fiber deposition was reduced,and the protein expressions of CPT-1 and CD36 in myocardial tissue increased(P<0.05).Conclusion Yixintai may improve myocardial energy metabolism and treat heart failure by increasing the expression of CPT-1 and CD36 protein in myocardial tissue and promoting fatty acid β oxidation.

The irrational use of Chinese patent medicines （CPM） is becoming more and more prominent， which makes the demand for clinical practice guidelines of CPM gradually increase. In order to make domestic scholars understand the latest developments and existing problems of the CPM guidelines， and promote its development， this paper introduced the concept of CPM guidelines， summarized the characteristics of the two development modes， namely “taking CPM as the key” and “taking disease/syndrome as the key”， and analyzed the current methodological status of developing and reporting CPM guidelines. Based on the existed problems， three suggestions have been put forward to optimize the quality of CPM guidelines， which were clarifying the target users and scope of CPM guidelines， establishing an open and transparent mechanism of the personnel involvement and process steps， and formulating implementable and operable recommendations for the use of CPM.

Background:Intestinal microbiota dysbiosis and impaired intestinal barrier,leading to bacterial translocation,are involved in acute pancreatitis(AP)exacerbation.Antimicrobial peptides participate in the regulation of intestinal microbiota,yet their changes and roles in the course of AP are unclear.Aims:To investigate the dynamic changes and significance of antimicrobial peptides in the ileum and pancreas among three classical AP models.Methods:Three AP mouse models were established by using cathelicidin plus lipopolysaccharide(CAE+LPS),sodium taurocholate(N-Tau)and L-arginine(L-Arg),respectively.The pathological changes of pancreatic and ileal tissues were observed and scored.Real-time PCR was applied to detect the expression levels of the proinflammatory cytokines,and antimicrobial peptides including lysozyme(LZM),secretory phospholipase A2(sPLA2),angiogenin 4(Ang4),regenerating islet-derived protein 3(REG3)family,β-defensin family,cathelicidin-related antimicrobial peptide(CRAMP),and glycoprotein 2(GP2)in ileum and/or pancreas.The association between expressions of antimicrobial peptides and the injuries of pancreas and ileum was analyzed.Results:Pancreatic and ileal injuries could be observed in all three AP models in different time points with various degrees.The pathological scores of the CAE+LPS and N-Tau models reached the highest level and then declined from 0-72 h,while those of L-Arg model progressively increased within 72 hours.Compared with the corresponding controls,the mRNA levels of LZM,sPLA2,and Ang4 in ileal tissue,and the mRNA levels of CRAMP,GP2,and β-defensins in pancreatic tissue,were generally downregulated in all three AP models(all P<0.05).CAE+LPS and N-Tau models showed a trend of initial decrease followed by partial recovery,while L-Arg model exhibited a gradual downregulation trend.The mRNA levels of REG3β and REG3γ in ileum upregulated and reached the peak at 48 h or 24 h and downregulated significantly at 72 h in all three AP models(all P<0.05);while in pancreatic tissue,both REG3β and REG3γ were generally upregulated in all three AP models(all P<0.05),but fell back in CAE+LPS and N-Tau models at 72 h.The mRNA levels of ileal β-defensins upregulated significantly in the early stage of the disease(12 h)in all three AP models(all P<0.05),and then gradually decreased.Spearman correlation coefficient analysis showed that the expressions of ileal LZM,sPLA2,and Ang4,as well as the pancreatic CRAMP,GP2,and β-defensins,were significantly negatively correlated with the pancreatic and ileal pathological scores in all three AP models(all P<0.05);but the expression of REG3β in the pancreas was significantly positively correlated with the pancreatic and ileal pathological scores(all P<0.05).Conclusions:The expressions of LZM,sPLA2,and Ang4 in the ileum,as well as the expressions of CRAMP,GP2,β-defensin family,and REG3β in the pancreas of the three classical AP models,dynamically changed with the severity of the disease.Ileal and pancreatic antimicrobial peptides may affect the injuries of pancreas and intestine during AP by regulating intestinal microbiota.

This study aimed to explore key quality control factors that affected the prognosis of intensive care unit (ICU) patients in Chinese mainland over six years (2015-2020). The data for this study were from 31 provincial and municipal hospitals (3425 hospital ICUs) and included 2 110 685 ICU patients, for a total of 27 607 376 ICU hospitalization days. We found that 15 initially established quality control indicators were good predictors of patient prognosis, including percentage of ICU patients out of all inpatients (%), percentage of ICU bed occupancy of total inpatient bed occupancy (%), percentage of all ICU inpatients with an APACHE II score ⩾15 (%), three-hour (surviving sepsis campaign) SSC bundle compliance (%), six-hour SSC bundle compliance (%), rate of microbe detection before antibiotics (%), percentage of drug deep venous thrombosis (DVT) prophylaxis (%), percentage of unplanned endotracheal extubations (%), percentage of patients reintubated within 48 hours (%), unplanned transfers to the ICU (%), 48-h ICU readmission rate (%), ventilator associated pneumonia (VAP) (per 1000 ventilator days), catheter related blood stream infection (CRBSI) (per 1000 catheter days), catheter-associated urinary tract infections (CAUTI) (per 1000 catheter days), in-hospital mortality (%). When exploratory factor analysis was applied, the 15 indicators were divided into 6 core elements that varied in weight regarding quality evaluation: nosocomial infection management (21.35%), compliance with the Surviving Sepsis Campaign guidelines (17.97%), ICU resources (17.46%), airway management (15.53%), prevention of deep-vein thrombosis (14.07%), and severity of patient condition (13.61%). Based on the different weights of the core elements associated with the 15 indicators, we developed an integrated quality scoring system defined as F score=21.35%xnosocomial infection management + 17.97%xcompliance with SSC guidelines + 17.46%×ICU resources + 15.53%×airway management + 14.07%×DVT prevention + 13.61%×severity of patient condition. This evidence-based quality scoring system will help in assessing the key elements of quality management and establish a foundation for further optimization of the quality control indicator system.
Humans ; China/epidemiology* ; Cross Infection/epidemiology* ; Intensive Care Units/statistics & numerical data* ; Quality Control ; Quality Indicators, Health Care/statistics & numerical data* ; Sepsis/therapy* ; East Asian People/statistics & numerical data*

Objective: To evaluate the efficacy and safety of Qili Qiangxin Capsule (QLQXC) combined with western medicine in patients with ischemic cardiomyopathy (ICM) comorbid with heart failure (HF) for clinical application. Methods: We searched relevant references in Chinese databases including China National Knowledge Infrastructure (CNKI), China Scientific Journal Database (VIP), Wanfang Database, and China Biology Medicine (CBM), as well as English databases including PubMed and Embase, from the foundation of the database to January 8, 2023, without language restrictions. All statistical analyses, including subgroup and sensitivity analyses, were performed using the Review Manager (version 5.4) and Stata (version 15.0). Results: QLQXC combined with western medicine significantly increased the endpoints of overall response rate (ORR) (P< 0.000 01), left ventricular ejection fraction (LVEF) (P< 0.000 01), the score of Minnesota Living with Heart Failure Questionnaire (MLHFQ) (P = 0.000 2), and 6-minute walking distance (6MWD) (P < 0.000 01), decreased left ventricular end-diastolic diameter (LVEDD) (P < 0.000 01), left ventricular end-systolic diameter (LVESD) (P = 0.03), and pro-brain natriuretic peptide (pro-BNP) (P < 0.000 01), and reduced the incidence of rehospitalization (P = 0.000 3) and adverse events (AEs) (P = 0.000 6) compared with those under the conventional western therapy alone. Nonetheless, no significant difference was observed in reducing the mortality between the QLQXC combined with western medicine group and the western medicine group (P = 0.30). Conclusion The combination therapy of QLQXC with western medicine can potentiate cardiac function and raise the quality of life in patients with ICM comorbid with HF.