OBJECTIVE To construct a risk prediction model for nonattainment plasma concentration of zonisamide in children with epilepsy， and to provide evidence for individualized dosing.METHODS Children with epilepsy who received standardized zonisamide treatment orally in Kunming Children’s Hospital were retrospectively selected as research subjects. Those treated from May 2022 to May 2024 were included in the modeling cohort， and those treated from June 2024 to January 2025 were included in the external validation cohort. According to plasma concentration， children were divided into therapeutic group and nonattainment group. Independent influencing factors for nonattainment plasma concentration of zonisamide were screened by collinearity diagnosis， univariate analysis， Lasso regression and random forest， based on which a nomogram risk prediction model was constructed and validated. Finally， the Shapley additive explanations （SHAP） method was used to interpret the features of the nomogram risk prediction model.RESULTS A total of 945 children with epilepsy were included in this study. There was no statistically significant difference in baseline data between the modeling cohort （531 cases） and the external validation cohort （414 cases） （ P ＞0.05）， indicating comparability. Through multi-stage feature screening， seven influencing factors were finally included to construct the prediction model， namely gender， age， dosage， aspartate transferase， total bilirubin， uric acid and vitamin D. The corrected area under the curve of the model was 0.799 in the modeling cohort and 0.762 in the external validation cohort， showing good calibration and clinical applicability. SHAP analysis showed that gender， dosage， total bilirubin， age and aspartate transferase were the top five important variables affecting model prediction.CONCLUSIONS The nomogram risk prediction model for nonattainment plasma concentration of zonisamide constructed in this study has stable predictive performance. Clinically， the risk of nonattainment plasma concentration can be quickly assessed by combining the child’s gender， age， dosage， liver and kidney function， and vitamin D， and the dosing regimen can be adjusted in time.

Objective To explore prescription medication rules and potential mechanism of traditional Chinese medicine(TCM)in the treatment of alcoholic liver disease(ALD)based on the technology of data mining and network pharmacology.Methods The prescriptions related to the treatment of ALD were retrieved in Chinese National Knowledge Infrastructure,Wanfang,Chinese Biomedical Literature and VIP databases.After the data were collated according to the filter criteria,IBM SPSS Statistics 27.0 and IBM SPSS Modeler 18 software were used to analyze the prescription rules and association rules.Then,the medication rules of TCM in the treatment of ALD were summarized,and the core drug combinations were obtained.Active ingredients in the core drug combinations for ALD and their targets were screened by network pharmacology.GO and KEGG analysis were performed on the main targets,and molecular docking technique was used to verify the binding ability of active ingredients to main targets.Results A total of 143 prescription for ALD were screened,involving 222 Chinese medicine,among which 28 high-frequency Chinese medicine were used with a frequency≥25 times.Eight core drug combinations were obtained by associations rule analysis.It has been found that there are 215 intersection targets between"Poria-Atractylodis macrocephalae Rhizoma-Hearba Artemisiae Scopariae"and ALD,including six core targets of AKT1,TNF,VEGFA,IL-1β,SRC,EGFR.One hundred and sixty-eight of signaling pathways are involved,including cancer pathways,PI3K/AKT signaling pathways,chemical carcinogenesis-reactive oxygen species,lipid and atherosclerosis,etc.Molecular docking results showed that the main active components including cerevisterol,genkwanin and demethoxycapillarisin had good binding ability to AKT1.Conclusion The main active ingredients in"Poria-Atractylodis macrocephalae Rhizoma-Hearba Artemisiae Scopariae"can participate in the regulation of key signaling pathways such as PI3K/AKT by acting on key target proteins(AKT1,TNF,and VEGFA).Subsequently,they play a role in inhibiting inflammatory response and apoptosis,slowing down liver fibrosis,and promoting hepatocyte repair.This study provides data support and theoretical guidance for the study of TCM in the treatment of ALD.

Objective:To investigate the factors associated with delay in anticoagulant therapy in patients with cerebral venous sinus thrombosis (CVST) and its effect on outcome.Methods:Patients with CVST admitted to Changhai Hospital, Naval Medical University from January 2010 to August 2021 were retrospectively enrolled. Patients were divided into early anticoagulation group and late anticoagulation group by the median time interval from first symptom to initiation of anticoagulation. The modified Rankin Scale was used for outcome assessment at 90 d after onset. 0-2 scores were defined as good outcome and 3-6 were defined as poor outcome. Demographic and clinical data were compared for the early versus late anticoagulation group and for the good versus poor outcome groups. Multivariable logistic regression was used to identify independent influencing factors of delay in anticoagulation and the correlation of delay in anticoagulation with poor outcome. Results:A total of 131 patients were included, their age was 40.07±15.11 years old, and 68 (51.91%) were male. Of these, 65 patients (49.62%) were in the early anticoagulation group and 14 (10.69%) were in the poor outcome group. Compared with the late anticoagulation group, the early anticoagulation group had a significantly higher proportion of patients with seizures and brain parenchymal damage as well as higher D-dimer levels on admission, while the proportion of patients with visual impairment/papilloedema was significantly lower (all P<0.05). Compared with the good outcome group, the poor outcome group had significantly higher proportions of patients with seizures, dyskinesia, impaired consciousness, low Glasgow Coma Scale score, and brain parenchymal damage as well as higher D-dimer, total cholesterol and low density lipoprotein cholesterol levels, sites of thrombus involvement were more common in the superior sagittal and straight sinuses, and significantly lower proportions of patients with headache and lower albumin levels on admission (all P<0.05). Multivariate logistic regression analysis showed that visual impairment/papilloedema (odds ratio [ OR] 0.119, 95% confidence interval [ CI] 0.030-0.473; P=0.002) and brain parenchymal damage ( OR 1.341, 95% CI 1.042-1.727; P=0.023) were independently associated with a delay in anticoagulation treatment, and a delay in anticoagulation treatment ( OR 6.102, 95% CI 1.185-30.504; P=0.030) and D-dimer level on admission ( OR 1.299, 95% CI 1.141-1.480; P<0.001) were the independent predictors of poor outcome in patients with CVST. Conclusions:Visual impairment/papilloedema and absence of brain parenchymal damage on cranial imaging are the independent risk factors for delay in anticoagulation in patients with CVST. The delay in anticoagulation is strongly associated with the poor outcome in patients with CVST.

Objective:To observe the effect of combining scalp acupuncture with hyperbaric oxygen on serum homocysteine and highly-sensitive c-reactive protein levels and functional recovery after cerebral infarction.Methods:A total of 101 survivors of cerebral infarction were divided randomly into a scalp acupuncture group ( n=33), a hyperbaric oxygen group ( n=34) and a combined treatment group ( n=34). All received routine treatment plus the appropriate supplementary treatment once a day for 10 days. The subjects were evaluated before the experiment as well as 10 and 90 days afterward. The National Institutes of Health′s stroke scale (NIHSS) was used to quantify neurological deficits and the Barthel Index quantified ability in the activities of daily living. Ninety days after the treatment, modified Rankin scale scores were also assigned. The levels of serum homocysteine (Hcy) and highly-sensitive c-reactive protein (hs-CRP) before and after 10 days of treatment were also compared among the 3 groups. Results:The average NIHSS and Barthel Index scores of all three groups had improved significantly after 10 days of treatment and the improvements persisted at the follow-up 3 months later. Both results were significantly better in the combined treatment group than in the scalp acupuncture group at the 90-day follow-up evaluation. The average Rankin score of the combined treatment group was lower at the last follow-up. Compared with before the intervention, the average Hcy of the scalp acupuncture group, the average hs-CRP of the hyperbaric oxygen group, as well as the average Hcy and hs-CRP of the combined treatment group were significantly lower after 10 days of treatment. Compared with the scalp acupuncture group, the average Hcy [(11.68±2.6) μmol/L] of the combined treatment group was significantly lower after the 10 days of treatment.Conclusions:Supplementing scalp acupuncture with hyperbaric oxygen therapy improves the long-term outcomes of cerebral infarction, reducing the level of serum Hcy.

Objective: To investigate the influential factors for failure of enhanced recovery after surgery(ERAS) from hepatectomy for hepatocellular carcinoma(HCC) patients and then to establish a risk prediction model. Methods: The relevant clinical data of 180 patients with HCC undergoing hepatectomy at Department of Hepatic Surgery, Affiliated Provincial Hospital, Anhui Medical University from January 2016 to June 2017 were analyzed retrospectively.There were 149 male patients and 31 female patients aging of (56.5±11.0)years(from 33 to 84 years old). The factors affecting postoperative failure of ERAS of HCC patients were identified by univariate and multivariate analyses, and then, all the obtained factors and their statistical values were used to establish the risk prediction model. Results: A total of 23 patients failed in the ERAS protocol(12.8%). The preoperative total bilirubin (TBIL), alanine aminotransferase(ALT) and amount of intraoperative bleeding were independent risk factors for failure of ERAS from hepatectomy(all P<0.05). The obtained risk prediction model was presented as follows: risk coefficient(R)=0.114×(TBIL)+ 0.082×(ALT)+ 0.008×(amount of intraoperative bleeding). At the cut of value of R=7.90, the area under the ROC curve of this model for predicting failure of ERAS was 0.866(95%CI: 0.788-0.945, P<0.01), with the sensitivity and specificity of 69.6% and 91.1%, respectively.External validation results indicated that the scoring system had good differential ability(area under the ROC curve=0.889, 95%CI: 0.811-0.967, P<0.01). Conclusions Higher level of preoperative TBIL(>21 μmol/L) and ALT(>50 U/L) and the larger amount of intraoperative bleeding (more than 400 ml) are independent risk factors for failure of ERAS inpatients undergoing hepatectomy for HCC and the established prediction model may have certain value for risk assessment.

Objective To evaluate the effects of dexmedetomidine plus sufentanil during postoperative analgesia on sleep quality in patients undergoing abdominal hysterectomy.Methods Sixty patients (aged 30-55 years,ASA Ⅰ or Ⅱ) scheduled for hysterectomy were randomly divided into the following 2 groups: group C (n=30,sufentanil) and group D (n=30,sufentanil plus dexmedetomidine).Polysomnography measures were performed,the night before surgery (PSG1),the first night after surgery (PSG2),and the second night after surgery (PSG3).In addition,pain levels (visual analogue scale,VAS),sedation levels,sufentanil consumptions,and possible adverse effects on MAP,HR and SpO2 were investigated.Results Compared with PSG1,N1 stage sleep in group C and N2 stage sleep in group D were significantly increased (P<0.05),N1 stage sleep at PSG2 and PSG3 in group D was decreased (P<0.05);N3 and REM stage sleep,sleep efficiency index and subjective sleep quality were decreased,arousal index was increased in two groups (P<0.05).Compared with group C,N1 stage sleep was decreased,and N2 stage sleep was increased at PSG2 and PSG3 in group D (P<0.05);sleep efficiency index,subjective sleep quality were increased,arousal index in group D was decreased (P<0.05).Patients in group D had a lower VAS score and cumulative sufentanil consumption,MAP,HR at 6,24,48 h after surgery (P<0.05) and a higher sedation score at 6,24 h after surgery than those in group C (P<0.05).Conclusion Besides offering effective analgesia,postoperative dexmedetomidine infusion has positive effects on sleep disturbance in patients undergoing hysterectomy.