Vancomycin is a glycopeptide antibiotic widely used for severe infections caused by gram-positive bacteria. Nevertheless， its clinical application is limited by a narrow therapeutic window and inter-individual differences in pharmacokinetics. Conventional dosing regimens rely on clinical experience and population pharmacokinetic models， which make precise therapy difficult. The emergence of machine learning provides new insights into tackling the above challenges. By integrating multi-dimensional data including demographic characteristics， clinical indicators and combined medications， machine learning can assist individualized medication for patients and improve the capacity for vancomycin dose prediction， in vivo exposure assessment and renal toxicity risk warning. However， the application of machine learning still faces multiple challenges such as poor data quality， weak model generalization ability and insufficient interpretability. Its clinical value needs to be further confirmed by prospective studies and external validation. Future research may consider deep integration of machine learning and population pharmacokinetic models to better support vancomycin individualized medication.

Objective:To evaluate the causal relationship between IL-7 and IL-7Rα and ankylosing spondylitis(AS)using the Mendelian randomization(MR)method.Methods:This study was based on gene-wide association study(GWAS)summary data,con-structing instrumental variables(IV)using single nucleotide polymorphisms(SNPs).We respectively adopt Inverse variance weighted(IVW),MR-Egger mode and Weighted median(WM)mode to assess the causal relation between IL-7/IL-7Rα and AS.In addition,we also conducted sensitivity tests,including the heterogeneity test,the pleiotropy test,the leave-one-out approach and the MR-PRESSO test.Results:IL-7 and IL-7Rα were respectively included in 9 and 5 IVs that could be used for MR analysis.Results of IVW analysis revealed a reliable causal relationship between IL-7 and IL-7Rα and AS[IL-7:P=0.025 2,OR(95%CI)=0.999 4(0.989 1～0.999 9);IL-7Rα:P=0.008 3,OR(95%CI)=1.000 6(1.000 2～1.001 0)].Cochranes Q test(IL-7:P=0.999 7;IL-7Rα:P=0.946 9)showed that all studies had good homogeneity.The results of a leave-one-out sensitivity analysis suggested that causal associations were not strongly influenced by any selected IVs.The intercept of the MR-Egger regression further showed that pleiotropy did not bias the causal effect in this study.Conclusion:Both IL-7 and IL-7Rα have a strong causal relationship with AS,among which IL-7 is a protec-tive factor for AS,and IL-7Rα is a risk factor for AS.

Objective To evaluate the efficacy and safety of polyethylene glycol electrolyte powder(PEG)combined with linaclotide(Lin)for bowel preparation in elderly constipated patients before colonoscopy.Methods In this prospective,randomized controlled trial,90 elderly patients with constipation undergoing colonoscopy were recruited at our hospital from June 2022 to December 2023.Participants were randomly assigned to three groups(n=30 each):PEG-3L alone,PEG-3L+Lin,and PEG-2L+Lin.Primary outcome was Boston Bowel Preparation Scale(BBPS)score and secondary outcomes included adverse event rates,colonoscopy completion rate,withdrawal time,and polyp detection rate.Statistical analysis was performed using independent t-tests and chi-square tests.Results The PEG-3L+Lin group achieved significantly higher BBPS scores than both PEG-3L alone and PEG-2L+Lin groups did(both P<0.001).The PEG-2L+Lin group also outperformed the PEG-3L alone group in cleansing efficacy(90.0%vs.76.7%,P=0.008).The PEG-2L+Lin group demonstrated the best tolerability and lowest adverse event rate,the PEG-3L group had the longest withdrawal time(P<0.05),but the three groups showed no significant difference in polyp detection rates.Conclusion PEG combined with linaclotide significantly improves bowel cleansing in elderly constipated patients.PEG-2L+Lin regimen provides optimal balance between efficacy,safety,and tolerability,making it a preferable choice for this population.

The American Heart Association(AHA)/American Stroke Association(ASA)published the"2024 Guidelines for Primary Stroke Prevention"in the Stroke journal on October 21,2024.This document summarized the clinical research and epidemiological data since the publication of the previous version of the guidelines in 2014,providing strategies and recommendations for stroke prevention across the entire lifecycle.The guidelines emphasized the importance of pharmacological treatment,routine screenings,and lifestyle changes,with updated and refined recommendations.This article dissects the newly revised sections of the guidelines,with a special focus on the management of blood pressure,blood glucose,and blood lipids levels,as well as customized advice for particular populations and patient subgroups.Furthermore,it explores health behavior management strategies,including diet and exercise,by intergarting the knowledge from the previous version of the primary stroke prevention guidelines with pertinent domestic and international materials.The ultimate objective is to offer valuable insights and guidance to China in advancing primary stroke prevention efforts and formulating coherent guidelines and consensuses within this critical domain.

Objective:This study aimed to evaluate the effects of hypertensive disorders of pregnancy (HDP), including their clinical subtypes, on neonatal heel blood methionine levels and explore potential dose-effect relationships.Methods:A retrospective cohort study was conducted among 11 007 singleton pregnancies and their neonates delivered at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, from July 2021 to October 2022. Participants were stratified into an HDP group [ n=992; 480 with gestational hypertension, 512 with preeclampsia (including 229 severe cases)] and a non-HDP control group ( n=10 015). Methionine concentrations were measured using tandem mass spectrometry from heel blood dried filter paper samples collected within 72 hours post-delivery. Statistical analyses included non-parametric tests to compare intergroup differences, multiple linear regression to evaluate the effects of HDP on methionine levels, and multivariate logistic regression to identify risk factors for hypermethioninemia (>50 μmol/L). Results:(1) Baseline data: Maternal age was higher in the HDP group compared to controls [33 (30-36) vs. 33 (30-35) years, Z=－2.29, P=0.022], with elevated pre-pregnancy body mass index (BMI) [23 (21-26) vs. 21 (20-23) kg/m2, Z=－17.15, P<0.001] and increased gestational hyperglycemia prevalence [26.5% (263/992) vs. 19.8% (1 986/10 015), χ2=27.95, P<0.001]. (2) Methionine level: Neonates in the HDP group exhibited higher methionine levels [25.96 (21.58-30.89) vs. 24.77 (20.45-29.53) μmol/L, Z=－5.26, P<0.001], with a severity-dependent gradient: gestational hypertension [25.83 (21.77-30.61)], preeclampsia [26.05 (21.23-31.11)], and severe preeclampsia [26.15 (21.25-32.13)] ( Z=2.97, 3.92, 2.26; all P<0.05). Trend analysis confirmed a dose-effect relationship between HDP and neonatal methionine ( χ2=7.82, P=0.005). (3) Multivariate analysis: After adjusting for confounding factors such as maternal age and BMI, HDP remained independently associated with elevated methionine levels ( β=0.93, 95% CI: 0.47-1.40, t=3.92, P<0.001) and increased hypermethioninemia risk ( OR=2.75, 95% CI: 1.13-6.68). Subgroup analysis revealed ORs of 3.20 (95% CI: 1.07-9.57) for gestational hypertension, 3.25 (95% CI: 1.09-9.72) for preeclampsia, and 5.23 (95% CI: 1.54-17.82) for severe preeclampsia (all P<0.05). (4) Neonatal outcomes: Neonates in the HDP group had lower birth weights [3 230 (2 910-3 560) vs. 3 335 (3 070-3 600) g, Z=－7.43, P<0.001] and higher fetal growth restriction rates [10.3% (102/992) vs. 3.1% (306/10 015), χ2=136.47, P<0.001]. Conclusions:HDP demonstrates an elevation of neonatal methionine levels, correlating with disease severity, particularly in severe preeclampsia. These findings underscore the necessity for enhanced metabolic monitoring and long-term follow-up in offspring of mothers with HDP, especially those with severe preeclampsia.

Objective:To evaluate the causal relationship between IL-7 and IL-7Rα and ankylosing spondylitis(AS)using the Mendelian randomization(MR)method.Methods:This study was based on gene-wide association study(GWAS)summary data,con-structing instrumental variables(IV)using single nucleotide polymorphisms(SNPs).We respectively adopt Inverse variance weighted(IVW),MR-Egger mode and Weighted median(WM)mode to assess the causal relation between IL-7/IL-7Rα and AS.In addition,we also conducted sensitivity tests,including the heterogeneity test,the pleiotropy test,the leave-one-out approach and the MR-PRESSO test.Results:IL-7 and IL-7Rα were respectively included in 9 and 5 IVs that could be used for MR analysis.Results of IVW analysis revealed a reliable causal relationship between IL-7 and IL-7Rα and AS[IL-7:P=0.025 2,OR(95%CI)=0.999 4(0.989 1～0.999 9);IL-7Rα:P=0.008 3,OR(95%CI)=1.000 6(1.000 2～1.001 0)].Cochranes Q test(IL-7:P=0.999 7;IL-7Rα:P=0.946 9)showed that all studies had good homogeneity.The results of a leave-one-out sensitivity analysis suggested that causal associations were not strongly influenced by any selected IVs.The intercept of the MR-Egger regression further showed that pleiotropy did not bias the causal effect in this study.Conclusion:Both IL-7 and IL-7Rα have a strong causal relationship with AS,among which IL-7 is a protec-tive factor for AS,and IL-7Rα is a risk factor for AS.

In 2024,the Japanese Circulation Society(JCS)and the Japanese Heart Rhythm Society(JHRS)jointly released the updated guidelines for the management of cardiac arrhythmias.The guideline provided updates on strategies for arrhythmias management,including device therapy,catheter ablation,pharmacological treatment and comprehensive management of atrial fibrillation(AF).This article focuses on the management of AF,including stroke risk assessment,oral anticoagulation therapy,high-risk patients management,comprehensive strategies,and lifestyle interventions.The guideline proposed a new stroke risk scoring tool,the HELT-E2 S2 score,refined the management of anticoagulation therapy in special high-risk patients,and updated comprehensive management strategies and lifestyle interventions for AF.These updates aim to enhance the prognosis and quality of life for AF patients,and also provide valuable insights for the management optimization of AF patients in China.

Objectives:To analyze whether there is a causal relationship between plasma proteins and the risk of coronary atherosclerosis(CAS)based on a two-sample Mendelian randomization(MR)analysis and to identify potential therapeutic targets for CAS.Methods:Single nucleotide polymorphisms(SNP)associated with plasma proteins from the UK Biobank Pharmacoproteomics Program(UKB-PPP)database were used as instrumental variables and outcome data were obtained from genome-wide association study databases.The Wald ratio method and inverse variance weighted(IVW)method in two-sample MR were employed as the primary approaches to assess the causal relationship between plasma proteins and CAS.Colocalization analysis was conducted as a sensitivity analysis to ensure the robustness of the MR findings.Results:A total of 132 plasma proteins were found to have causal associations with an increased risk of CAS.Colocalization analysis revealed that 12 plasma proteins shared genetic variants with CAS.Among them,Proprotein convertase subtilise/kexin type 9(PCSK9)(OR=1.23,95%CI:1.15-1.32,P<0.01)and neurocan(NCAN)(OR=1.35,95%CI:1.21-1.52,P<0.01)exhibited posterior probability of hypothesis4(PPH4)values<0.80 in the colocalization analysis,indicating strong support for colocalization and suggesting their potential as primary plasma protein drug targets for CAS.Conclusions:PCSK9 is associated with an increased risk of CAS and is confirmed as a therapeutic target for CAS.NCAN emerges as another potential therapeutic target for CAS.

Objective:To compare the efficacy of robot-assisted percutaneous reduction and screw fixation versus open reduction and plate fixation via the sinus tarsi approach in the treatment of Sanders types II and III calcaneal fractures.Methods:A retrospective cohort study was conducted to analyze the clinical data of 82 patients (90 feet) with calcaneal fractures admitted to the Department of Orthopedic Trauma, Beijing Jishuitan Hospital, Capital Medical University from January 2020 to April 2024, including 74 males and 8 females, aged 24-87 years [(46.4±12.1)years]. According to Essex-Lopresti classification, the fractures were classified as tongue-type in 43 patients and joint-collapse-type in 47. According to Sanders classification, 69 feet were classified as type II and 21 as type III. Forty-seven patients (52 feet) were treated with robot-assisted percutaneous reduction and screw fixation (screw fixation group) and 35 (38 feet) with open reduction and plate fixation via the sinus tarsi approach (plate fixation group). The two groups were compared in terms of the operation duration, intraoperative blood loss, length of hospital stay and time to weight-bearing. The width, height, length, B?hler angle and Gissane angle of the calcaneus before surgery and at 1 day after surgery were compared. The Maryland foot and ankle function score, American Orthopedic Foot and Ankle Society (AOFAS) ankle and hindfoot function score, and visual analogue scale (VAS) score at 1, 3 months postoperatively, and at the last follow-up were compared. The incidence of postoperative complications and removal rate of internal fixation were also detected in the two groups.Results:All the patients were followed up for 9-60 months [(30.0±14.5)months]. There was no significant difference in the operation duration between the two groups ( P>0.05). The intraoperative blood loss, length of hospital stay and time to weight-bearing in the screw fixation group were 10.0(10.0, 20.0)ml, 7.0(5.0, 8.0)days and (5.0±0.8)weeks, which were significantly less or shorter than 30.0(20.0, 50.0)ml, 8.0(6.0, 11.0)days and (6.9±0.7)weeks in the plate fixation group ( P<0.05). The width, height, length, B?hler angle and Gissane angle of the calcaneus at 1 day after surgery were (43.4±4.2)mm, (46.2±4.0)mm, (81.6±5.1)mm, 27.1(20.4, 30.4)° and (113.4±10.1)° in the screw fixation group, which were all improved compared with those before surgery [(47.8±4.6)mm, (39.3±4.8)mm, (79.2±5.9)mm, 9.5(0.0,16.5)° and (119.3±13.4)°] ( P<0.01). The width, height, length and B?hler angle of the calcaneus at 1 day after surgery were (41.6±5.7)mm, (48.4±4.8)mm, (83.1±5.7)mm and 27.3(21.3, 31.6)° in the plate fixation group, which were all improved compared with those before surgery [(47.8±5.0)mm, (41.7±5.1)mm, (80.1±5.9)mm and 12.9(7.2,19.8)°] ( P<0.01), with no significant difference in the Gissane angle ( P>0.05). Before surgery and at 1 day postoperatively, no significant differences were found in the width, length, B?hler angle or Gissane angle of the calcaneus between the two groups ( P>0.05), while the height of the calcaneus in the screw fixation group was lower than that in the plate fixation group ( P<0.05). At 1 month after surgery and at the last follow-up, there were no significant differences in the Maryland foot and ankle function score, AOFAS ankle and hindfoot function score, and VAS score between the two groups ( P>0.05). At 3 months after surgery in the screw fixation group, the Maryland foot and ankle function score was (79.7±3.8)points, significantly higher than (74.7±2.8)points in the plate fixation group ( P<0.01); the AOFAS ankle and hindfoot function score was (77.1±5.0)points, significantly higher than (70.1±3.6)points in the plate fixation group ( P<0.01); the VAS score was 1.0(1.0, 2.0)points, significantly lower than 2.5(2.0, 3.0)points in the plate fixation group ( P<0.01). No significant difference was detected in the incidence of postoperative complications between the two groups ( P>0.05). The removal rate of internal fixation was 10% (5/52) in the screw fixation group, significantly lower than 29% (11/38) in the plate fixation group ( P<0.05). Conclusion:Compared with open reduction and plate fixation via the sinus tarsi approach, robot-assisted percutaneous reduction and screw fixation has the advantages of less intraoperative blood loss, shorter hospital stay, earlier weight-bearing exercises, better early functional recovery and pain relief, and lower internal fixation removal rate in the treatment of Sanders types II and III calcaneal fractures.

Objective:To observe the effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) at different frequencies on cognitive impairment due to high-altitude hypoxia.Methods:Sixty officers and soldiers displaying cognitive impairment in a hypoxic high-altitude environment were randomly divided into 15Hz, 20Hz and 25Hz groups, each of 20. They were given rTMS at those frequencies for 30 days. Before the stimulation and after 15 and 30 days, event-related potentials, latencies of mismatched negativity (MMN) and P300 signals were recorded. The participants′ cognition was also evaluated using the Montreal Cognitive Assessment Scale (MoCA). Correlation between the electrophysiological indexes and the MoCA scores was computed.Results:After 15 days, all had shorter MMN latencies, higher total MoCA scores and better memory scores. The only significant difference among the three groups was in the average memory scores. After 15 days, MMN latency was significantly negatively correlated with the memory scores in all three groups ( r=0.44 to -0.54). Conclusions:rTMS at frequencies above 15Hz can effectively relieve cognitive impairment, especially memory dysfunction, resulting from high-altitude hypoxia.