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 A clinical comprehensive evaluation of five biologic targeted drugs for the treatment of severe eosinophilic asthma （SEA） was conducted to provide objective evidence for the rational selection of these medications in medical institutions. METHODS Using the evaluation methods from the Chinese Medical Institution Drug Evaluation and Selection Rapid Guide （ Third Edition ）， the effectiveness， safety， pharmaceutical characteristics， cost-effectiveness， and other attributes of five biologics targeting SEA （omalizumab， mepolizumab， benralizumab， dupilumab， and tezepelumab） already marketed in China were quantitatively scored across five dimensions， and their recommendation levels were categorized based on the scores. RESULTS The comprehensive scoring results showed that mepolizumab scored 81.29， making it a highly recommended variety； benralizumab scored 78.05， dupilumab scored 77.84 and omalizumab scored 70.14，all of which are recommended varieties； tezepelumab scored 67.77， considered weakly recommended variety. CONCLUSIONS Mepolizumab shows excellent performance in eosinophil clearance， good accessibility， and is more cost-effective than the others， making it more selective in SEA treatment； omalizumab has more advantages in the treatment of SEA patients with elevated immunoglobulin E levels； dupilumab can be used as the preferred treatment for SEA patients with chronic obstructive pulmonary disease.

OBJECTIVE A clinical comprehensive evaluation of five biologic targeted drugs for the treatment of severe eosinophilic asthma （SEA） was conducted to provide objective evidence for the rational selection of these medications in medical institutions. METHODS Using the evaluation methods from the Chinese Medical Institution Drug Evaluation and Selection Rapid Guide （ Third Edition ）， the effectiveness， safety， pharmaceutical characteristics， cost-effectiveness， and other attributes of five biologics targeting SEA （omalizumab， mepolizumab， benralizumab， dupilumab， and tezepelumab） already marketed in China were quantitatively scored across five dimensions， and their recommendation levels were categorized based on the scores. RESULTS The comprehensive scoring results showed that mepolizumab scored 81.29， making it a highly recommended variety； benralizumab scored 78.05， dupilumab scored 77.84 and omalizumab scored 70.14，all of which are recommended varieties； tezepelumab scored 67.77， considered weakly recommended variety. CONCLUSIONS Mepolizumab shows excellent performance in eosinophil clearance， good accessibility， and is more cost-effective than the others， making it more selective in SEA treatment； omalizumab has more advantages in the treatment of SEA patients with elevated immunoglobulin E levels； dupilumab can be used as the preferred treatment for SEA patients with chronic obstructive pulmonary disease.

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 investigate the prevalence of Dengue virus (DENV) infection among voluntary blood donors in Xishuangbanna Dai Autonomous Prefecture, and to evaluate the necessity of implementing nucleic acid testing (NAT) for blood donors during the rainy season (May-October). Methods: Prior to initiating donor screening, the Xishuangbanna Central Blood Center conducted in-house validation of reagent performance and participated in external quality assessment (EQA) organized by the National Center for Clinical Laboratories (NCCL). During the surveillance period (August-October 2024), a total of 2 919 donor samples were screened using a 6-sample mini-pool NAT strategy. Daily internal quality controls were recorded. Samples that tested positive in pooled screening were deconvoluted and retested in duplicate; only those reactive in both replicate wells were sent to the NCCL for confirmatory testing. At NCCL, samples underwent re-testing using five domestic NAT reagents, as well as serological assays for NS1 antigen and DENV-specific IgG/IgM. Confirmed positive samples were further characterized by serotyping, envelope (E) gene sequencing, and phylogenetic analysis using the maximum likelihood method. Results: The DENV NAT reagent demonstrated consistent detection of 40 copies/mL controls in individual donor (ID)-NAT test (mean CT: 35.61±0.40). During the 63-day quality control monitoring, DENV detection remained stable (mean CT: 22.53±0.72). The center achieved full marks in EQA assessments for 2023 and 2024. Three reactive pools were identified in initial screening, and subsequent individual testing confirmed three DENV RNA-positive donors (sample numbers: 2401, 2402, and 2403). The confirmatory test results from NCCL were: all five NAT platforms consistently detected DENV RNA in the three samples; for serological tests, 2 samples (2402, 2403) were positive for NS1 antigen, while all three samples were negative for both IgG and IgM antibodies. DENV serotyping reagents identified DENV-2 in all cases, which were further confirmed as DENV-2 Genotype Ⅱ-Cosmopolitan by E gene sequencing. Phylogenetic analysis indicated that samples 2401 and 2402 clustered with Southeast Asian strains (Thailand/MZ636802.1, Laos/PQ775621.1), while sample 2403 closely matched a previously reported local Yunnan strain (PV544686.1). Conclusion: DENV-2 infection was detected among blood donors in Xishuangbanna during the rainy season, indicating concurrent risks of imported and local transmission. We recommend implementing pooled NAT screening for blood donors in high-risk areas during dengue epidemic seasons, along with strengthened laboratory quality control, to enhance blood safety.

Objective Wearable devices refer to a class of monitoring devices that can be tightly integrated with the human body and are designed to continuously monitor individual's activity without impeding or restricting the user's normal activities in the process. With the rapid advancement of chips, sensors, and artificial intelligence technologies, such devices have been widely used for patients with cardiovascular diseases who require continuous health monitoring. These patients require continuous monitoring of a number of physiological indicators to assess disease progression, treatment efficacy, and recovery in the early stages of the disease, during the treatment, and in the recovery period. Traditional monitoring methods require patients to see a doctor on a regular basis with the help of fixed devices and analysis by doctors, which not only increases the financial burden of patients, but also consumes medical resources and time. However, wearable devices can collect data in real time and transmit it directly to doctors via the network, thus providing an efficient and cost-effective monitoring solution for patients. In this paper, we will review the applications, advantages and challenges of wearable devices in the treatment of cardiovascular diseases, as well as the outlook for their future applications.

Objective To investigate the effect of Remazolam(RZ)on intestinal injury in burn sepsis rats by regulating the Notch-1/hairy and enhancer of split homolog(Hes)signaling pathway.Methods Sixty SPF grade SD male rats were randomly separated into Normal group,Model group,low-dose RZ group(RZ-L group,3 mg/kg RZ),high-dose RZ group(RZ-H group,6 mg/kg RZ)and high-dose RZ+Notch-1 activator Jagged1 group(RZ-H+Jagged1 group,6 mg/kg RZ+0.67 mg/kg Jagged1),with 12 rats in each group.A burn sepsis model was prepared by establishing a 20%total surface area(TBSA)third-degree burn(burn)model on the back of rats,followed by injection of Pseudomonas aeruginosa.HE staining was applied to observe rat ileum tissue's pathological changes and assess intestinal mucosal damage score(Chiu's score).ELISA method was used to detect the levels of serum endotoxin,D-lactate,diamine oxidase(DAO),interleukin(IL-6),tumor necrosis factor-α(TNF-α)and myeloperoxidase(MPO)in rats.RT-qPCR method was applied to detect the expression of Notch-1 and Hes mRNA in rat ileum tissue,and Western Blot was used to detect the expression of Notch-1/Hes signaling pathway-related proteins in rat ileum tissue.Results Compared with the Normal group,the intestinal mucosal injury score(5.30±0.48 vs 1.00±0.52),serum endotoxin(135.69±16.24 pg/ml vs 62.48±3.23 pg/ml),D-lactate(1403.58±68.97 pg/ml vs 752.06±25.29 pg/ml)and DAO levels(137.55±12.37 pg/ml vs 58.52±4.43 pg/ml),ileal tissue IL-6(186.45±16.37 ng/ml vs 21.32±3.66 ng/ml),TNF-α(163.37±11.40 ng/ml vs 15.52±1.03 ng/ml)and MPO levels(8.94±0.92 U/ml vs 2.35±0.33 U/ml),Notch-1 mRNA(1.86±0.19 vs 1.00±0.10)and protein(0.79±0.08 vs 0.21±0.02),Hes-1 mRNA(2.13±0.21 vs 1.00±0.12)and protein(0.88±0.09,0.32±0.03)expression levels in the Model group were greatly increased,and the differences were statistically significant(t=14.294～47.368,all P<0.05).Compared with the Model group,the corresponding indicators of the RZ-L and RZ-H groups showed opposite changes,and the differences were statistically significant(tRZ-L=5.650～21.448,tRZ-H=4.435～42.403,all P<0.05).The Notch-1 activator Jagged1 weakened the therapeutic effect of RZ on intestinal injury in burn sepsis rats.Conclusion RZ may alleviate intestinal injury in burn sepsis model rats by inhibiting the Notch-1/Hes signaling pathway.

Objective:To explore the value of immature platelets and thromboelastography (TEG) in evaluating bleeding tendency in patients bitten by blood venomous snakes.Methods:In December 2023, a bleeding scoring system was used to grade the bleeding score and degree of bleeding in 147 patients with blood venomous snake bites. Immature platelets and TEG were also tested to analyze the correlation between the bleeding degree of patients and indicators such as TEG, immature platelet ratio (IPF), and absolute value of immature platelets (A-IPF). The measurement data were represented by Mean±SD, and ANOVA was used for comparison among groups. Statistical data were analyzed using χ2 test. Spearman correlation was used to analyze the correlation between bleeding degree and the platelet count (PLT), immature platelet and TEG. Pearson linear correlation was used to analyze the correlation of PLT, immature platelets and TEG. The indexes of immature platelets and TEG were analyzed by receiver operating characteristic curve. Results:The 147 patients were graded for bleeding severity based on their bleeding scores, and divided into mild (22 cases), moderate (119 cases), and severe groups (6 cases), and the clinical data such as age, gender and the time from bite to visit were compared among the three groups. The differences were not statistically significant ( P>0.05). The coagulation reaction time (R), clot formation time (K), and immature platelet parameters (IPF, A-IPF) in TEG parameters increased with the degree of bleeding. PLT decreased with the degree of bleeding, and the difference was statistically significant ( P<0.05). Blood venomous snake bite patients have a negative correlation between PLT and IPF ( r=-0.301, P=0.012), but no correlation with A-IPF ( r=0.072, P=0.461) ; PLT was positively correlated with coagulation Angle (αAngle) and maximum thrombus amplitude (MA) of TEG ( r=0.220、0.243, P=0.028、0.015), but negatively correlated with R value and K value ( r=-0.368、-0.362, P<0.001). IPF is positively correlated with R and K values ( r=303、271, P=0.0020、0.035) ; IPF is not correlated with MA value and Angle angle, while A-IPF is positively correlated with R value ( r=0.162, P<0.001). The degree of bleeding in patients is positively correlated with R value ( r=0.237, P<0.001), but not with K value, MA value, and Angle angle ( P>0.05) ; The degree of bleeding in patients is correlated with PLT ( r=-0.411, P<0.001). The ROC curve analysis results show that the R value, K value, and MA value are effective in evaluating the bleeding risk of blood venomous snake bites in patients, and the PLT combined with A-IPF has the best efficacy in evaluating the bleeding risk of blood venomous snake bites in patients. Conclusion:The combination of PLT and A-IPF, TEG's R value, K value, MA value indicators can accurately evaluate the bleeding risk of blood venomous snake bites, and can be widely used in clinical practice as an important prediction method for bleeding tendency in patients bitten by blood venomous snakes.

OBJECTIVE: To analyze the clinical characteristics and genetic profile of patients with 46,XY Disorders of sex development (DSD) and a female phenotype in order to provide insights for the diagnosis and management of similar cases. METHODS: A retrospective analysis was conducted on 36 children with 46,XY DSD and a female phenotype who were treated at the Department of Endocrinology, Genetics and Metabolism of Henan Children's Hospital between March 1, 2016, and June 30, 2024. The evaluations included external genitalia scoring using the Prader scale and External Masculinization Score (EMS), imaging studies to assess gonadal development, and assessments of adrenal and gonadal function via adrenal hormone levels, sex hormone levels, and human chorionic gonadotropin (hCG) stimulation testing. Gender role behavior was assessed using gender role scales and sandplay therapy. Whole exome sequencing and Sanger sequencing were used to identify and validate genetic variants. A multidisciplinary team (MDT) comprehensively determined gender rearing based on molecular genetic diagnosis. This study was approved by the Medical Ethics Committee of Henan Children's Hospital (Ethics No.: 2024-K-105). RESULTS: The median age at initial consultation was 3 years and 1 month (range: 7 days to 16 years). Common symptoms included primary amenorrhea, clitoromegaly, and inguinal hernia. Fully feminized external genitalia were observed in 52.7% of the cases, and 80.5% had absence of the uterus. Internal gonads included absent gonads (5.6%), ovotestes (8.3%), streak gonads (5.6%), cryptorchidism (75.0%), and normally positioned testes (5.6%). At initial diagnosis, median luteinizing hormone (LH) was 1.305 IU/L, with elevated LH in 14 cases. Median follicle-stimulating hormone (FSH) was 4.87 IU/L, with elevated FSH in 17 cases. Median testosterone was 0.025 ng/mL. Median dihydrotestosterone (DHT) was 36.90 pg/mL. After hCG stimulation, median testosterone was 0.984 ng/mL and median DHT was 71.69 pg/mL. The testosterone/DHT ratio was elevated in one case (35.7). Testosterone levels remained below 1 ng/mL after hCG stimulation in 18 cases. Anti-Müllerian hormone (AMH) was decreased in 15 cases and increased in 3 cases. Inhibin B (InhB) was increased in 7 cases and decreased in 4 cases. Pathogenic variants were detected in 88.9% of the patients, involving AR (11 cases), CYP17A1 (4 cases), GATA4 (1 case), NR0B1 (1 case), NR5A1 (7 cases), SRD5A2 (1 case), WT1 (2 cases), STAR (4 cases), and LHCGR (1 case), totaling 34 variant sites. Among these, 9 variants were de novo, and 23 were inherited from parents. Sixteen variant sites were previously unreported. Gender assignment was male in 11 cases (30.6%) and female in 25 cases (69.4%). CONCLUSION Common symptoms in 46,XY DSD patients with a female phenotype include primary amenorrhea, clitoromegaly, and inguinal hernia. Elevated FSH, androgen deficiency, and decreased AMH and InhB may indicate testicular dysgenesis or impaired androgen synthesis. Adrenal insufficiency should raise suspicion for defects in steroid hormone synthesis pathway enzymes.
Humans ; Female ; Disorder of Sex Development, 46,XY/diagnosis* ; Child ; Male ; Phenotype ; Child, Preschool ; Retrospective Studies ; Adolescent ; Infant

Lemborexant is a new drug for the treatment of insomnia.It is a dual orexin receptor antagonist that competitively binds to two orexin receptors,OX1R and OX2R,inhibits orexin neuro-transmission,and regulates the sleep-wake rhythm.This article comprehensively reviews the discovery of the drug target,basic information,clin-ical studies,safety assessment,and limitation anal-ysis of lemborexant,aiming to provide a compre-hensive understanding of the current research sta-tus and achievements of this drug in clinical prac-tice.