Isavuconazole represents a novel gen-eration of triazole antifungal agents for the treat-ment of invasive trichothecenes in adults.The phar-macokinetic profile of isavuconazole differs in spe-cial populations,including children,patients with ex-tracorporeal membrane oxygenation,those with he-patic or renal injury,patients undergoing blood puri-fication,and critically ill individuals and solid organ transplant recipients.These differences impact the safety and efficacy of patient treatment.This article presents the latest progress in the pharmacokinetic study of isavuconazole in these special populations.

Objective:To identify genetic etiology of ischemic stroke(IS)based on pleiotropy of obe-sity related genes.Methods:A discordant sib-pair study was designed based on the Fangshan family co-hort in Beijing.Body mass index(BMI)polygenic risk score(PRS)was first constructed under different P values.Using the polygenic transmission disequilibrium test(pTDT),we then compared the actual BMI genetic risk of siblings with IS to their expected risk,to analyze whether higher BMI was over-trans-mitted to siblings with IS.The single nucleotide polymorphism(SNP)that comprised the PRS over-trans-mitted with IS and that corresponded to the highest heritability of IS were identified as a pleiotropy SNPs set between BMI and IS.This set was then utilized as a candidate set to identify and verify risk SNPs as-so-ciated IS by transmission disequilibrium test.Finally,we identified independent genomic risk loci and mapped to genes,we then explored the biological function of the identified risk loci and genes by func-tional annotation and pathway enrichment.Results:A total of 541 participants were enrolled,with an average age of(58.4±8.1)years,including 326 discordant sib pairs of ischemic stroke.Compared with non-IS participants,IS participants with males,education level below junior high school,hypertension and hyperlipidemia accounted for a higher proportion(P＜0.05).For all the BMI PRS,we found that the actual genetic risk of BMI in siblings with IS was higher than their expectation,suggesting that genetic risk associated with high BMI was over-transmitted with IS.Compared with other SNP sets,the set(P＜5 × 10-4)corresponded to the best analytical statistics of pTDT and the highest heritability of IS and was identified as the pleiotropy SNP set between BMI and IS.Within this set,there were 45 SNPs having linkage and association with IS,which were located in 43 independent genomic risk loci and mapped to 40 genes.These genes were significantly enriched in the lipid metabolism pathway.The rs2232852 cor-rected by multiple tests was mapped to CYB5R1 and ADIPOR1,which were related to lipid metabolism and the ferroptosis pathway.Conclusion:Pleiotropy between BMI-related genes and IS was observed.Forty-five SNPs were found with linkage and association with IS in the pleiotropy gene set and mapped to 40 genes,which were functionally enriched in lipid metabolic pathways.The rs2232852 corrected by multiple tests during association analysis validation was mapped to CYB5R1 and ADIPOR1,which were related to lipid metabolism and the ferroptosis pathway,suggesting that lipid metabolism and ferroptosis played an important role in the development of IS.

Objective: To explore the association between negative life events and smartphone addiction among middle school students, so as to provide theoretical support and practical guidance for prevention and intervention of smartphone addiction among middle school students. Methods: Using cluster sampling, 8 890 students were selected to survey from 27 junior high schools and 3 senior high schools in a district of Shenzhen in 2022 (baseline) and 2023 (followup). Data were collected through selfresigned questionnaires on basic information, the Smartphone Addiction Scale-Short Version, and the Adolescent Selfrating Life Events Checklist. Mixedeffects models were employed to analyze the association. Results: Compared to 2022, the punishment scores of middle school students in 2023 [1.00 (0.00, 6.00) and 1.00 (0.00, 6.00)] decreased (Z=4.27), while the scores of interpersonal stress, learning stress and adaptation [4.00(0.00, 8.00), 4.00(0.00, 8.00); 4.00(1.00, 8.00), 5.00(2.00, 9.00); 2.00 (0.00, 6.00), 3.00 (0.00, 7.00)] increased (Z=-3.04, -8.36, -6.80) (P<0.01). Mixedeffects models revealed a positive doseresponse relationship between negative life events and smartphone addiction (OR=1.08-1.17, P<0.01). Stepwise regression showed independent positive effects of interpersonal stress (OR=1.05), academic stress (OR=1.03), and adaptation stress (OR=1.11) on smartphone addiction (P<0.01). Subgroup analysis of nonaddicted students in 2022 confirmed persistent associations for academic stress (OR=1.03) and adaptation (OR=1.07) (P<0.01). Conclusion Negative life events exhibit a positive doseresponse relationship with smartphone addiction, particularly interpersonal stress, academic stress, and adaptationrelated events.

Objective: To explore the longitudinal association between only-child status and smartphone addiction among middle school students, so as to provide a basis for establishing family intervention measures for smartphone addiction in middle school students. Methods: In October 2022 and October 2023, a preliminary survey and follow-up were conducted among 8 759 middle and high school students from 30 schools in a district of Shenzhen. A self-designed questionnaire was used to determine whether the students were the only-child, and the Chinese Version of the Smartphone Addiction Scale-Short Version (C-SAS-SV) was utilized to assess the students smartphone addiction status. A multilevel mixed-effects model and subgroup analysis were applied to examine the association between only-child status and smartphone addiction among middle school students. Results: During 2022 to 2023, the prevalence of smartphone addiction in the cohort of middle school students increased from 24.1% to 25.2%. Compared with only-child, non-only child were more likely to be addicted to smartphones (adjusted model: OR =1.2, 95% CI =1.1-1.4) and also scored higher on smartphone addiction (adjusted model: β =0.9, 95% CI =0.2-1.5)( P <0.05). Subgroup analysis further revealed that compared to baseline, non-only child demonstrated an increased prevalence of smartphone addiction (adjusted model: OR = 1.2 , 95% CI =1.0-1.5) and higher addiction scores (adjusted model: β =0.8, 95% CI =0.2-1.5) after one year( P <0.05). Conclusions Non-only child face higher risk of smartphone addiction. Under the current population policy, it is crucial to address smartphone addiction among middle school students who is not only child.

Objective: To explore the potential causal association between adolescent compulsive behaviour and smartphone addiction based on longitudinal data, so as to provide reference for the establishment of adolescent smartphone addiction interventions. Methods: A preliminary survey and follow-up were conducted on 8 907 middle and high school students in a district of Shenzhen in 2022 and 2023, respectively. Compulsive behaviours were measured by using the Mental Health Inventory for Middle School Students-60 Items (MMHI-60), smartphone addiction was assessed by using the Smartphone Addiction Scale-Short Version ( SAS- SV), and the associations between compulsive behaviours and smartphone addiction were analysed by using multilevel mixed-effects models and subgroup analyses. Results: Smartphone addiction detection rates among middle school students were significantly associated with genders, father s education level, mother s education level, study load subgroups, and whether or not they were single-parent families, and there were statistical differences ( χ 2=17.21-175.34, P <0.05). Students with compulsive behaviours were 2.98 times more likely to develop smartphone addiction than those without compulsive behaviours ( OR=2.98, 95%CI=2.77-3.22, P <0.05). Subgroup analysis of middle school students without smartphone addiction in the first year found that compulsive behaviours significantly predicted smartphone addiction ( OR= 1.76 , 95%CI=1.54-2.01, P <0.05). Conclusion There is a potential causal association between obsessive-compulsive behaviours and smartphone addiction in middle school students, and obsessive-compulsive behaviours in middle school students could significantly predicted the occurrence of smartphone addiction.

Objective To investigate the protective effect of Notch1-regulated microglial polarization against epileptic seizure in mice.Methods The pentylenetetrazole(PTZ)kindling models of epilepsy were established in mice with normal(Notch1normal)and high(Notch1over)expression of the Notch1 protein,with Racine grade Ⅳ set as the standard,to evaluate the effect of Notch1 expression on sei-zure susceptibility.Microglial activation and polarization in the temporal lobe tissues of mice were detected using immunofluorescence staining,and the levels of inflammatory cytokines in the temporal lobe tissues was detected using an enzyme-linked immunosorbent assay.Results High Notch1 expression showed high resistance to seizures.Compared with the Notch1normal+Sal group,the relative fluorescence intensity of Iba1,CD16,and Arg1 proteins in the temporal lobes of mice in the Notch1normal+PTZ group,as well as the TNF-α,IL-6,and IL-10 levels significantly increased(P＜0.05).Compared with the Notch1nornal+PTZ group,the relative fluorescence intensity of Iba1 and CD16 proteins in the temporal lobes of mice in the Notch1over+PTZ group significantly decreased(P＜0.05),the relative fluorescence intensity of Arg1 protein significantly increased(P＜0.05),the TNF-α and IL-6 levels significantly decreased(P＜0.05),and the IL-10 level further increased(P＜0.05).Conclusion High Notch1 protein expression significantly enhanced M2-type microglial polari-zation,inhibited M1-type microglial polarization,and increased resistance to seizure susceptibility in mice.

Objective To evaluate the accuracy of 6 commercial antibiotic susceptibility testing methods in detecting the sensitivity of carbapenems-resistant Klebsiella pneumoniae(CRKP)to tigecycline,and to provide an evidence for clinical laboratory to select the appropriate tigecyline susceptibility tests.Methods Non-duplicate CRKP clinically isolated from Aerospace Center Hospital from June 2023 to February 2024 were collected.60 cases of tigecycline intermediated CRKP[minimal inhibitery concentration(MIC)=4μg/ml]and 60 cases of drug-resistant CRKP(MIC≥8μg/ml)were screened by Vitek-2.The sensitivity of CRKP to tigecycline was detected by different methods.With the MIC test strip(MTS)as the reference method,the methodological evaluation of Vitek-2,commercial broth dilution method,E-test,Kirby-Bauer disk diffusion(KB)and disk combined with resensitization bufferwas carried out under the interpretation standards of the U S Food and Drug Administration(FDA)and the European Commission for Drug Susceptibility Testing(EUCAST),respectively.Results For the intermediate strains,under the FDA criteria,both the commercial broth dilution method and the disk combinedwith resensitization buffer method showed high consistency with the MTS method and were acceptable,whereas under the EUCAST criteria,all five methods were unacceptable.For the resistant strains,no matter what standard was,CA of all five methods were less than 90%,which were unacceptable.For all strains as a whole,the results were consistent with those of the resistant ones.Conclusion Under the current sample size,none of the five methods met the acceptable standards,especially not suitable for the recheck of strains with higher MICs.Commercial broth dilution method have the highest consistency with MTS,and it is worth expanding the sample size for further study.

Objective To evaluate the accuracy of 6 commercial antibiotic susceptibility testing methods in detecting the sensitivity of carbapenems-resistant Klebsiella pneumoniae(CRKP)to tigecycline,and to provide an evidence for clinical laboratory to select the appropriate tigecyline susceptibility tests.Methods Non-duplicate CRKP clinically isolated from Aerospace Center Hospital from June 2023 to February 2024 were collected.60 cases of tigecycline intermediated CRKP[minimal inhibitery concentration(MIC)=4μg/ml]and 60 cases of drug-resistant CRKP(MIC≥8μg/ml)were screened by Vitek-2.The sensitivity of CRKP to tigecycline was detected by different methods.With the MIC test strip(MTS)as the reference method,the methodological evaluation of Vitek-2,commercial broth dilution method,E-test,Kirby-Bauer disk diffusion(KB)and disk combined with resensitization bufferwas carried out under the interpretation standards of the U S Food and Drug Administration(FDA)and the European Commission for Drug Susceptibility Testing(EUCAST),respectively.Results For the intermediate strains,under the FDA criteria,both the commercial broth dilution method and the disk combinedwith resensitization buffer method showed high consistency with the MTS method and were acceptable,whereas under the EUCAST criteria,all five methods were unacceptable.For the resistant strains,no matter what standard was,CA of all five methods were less than 90%,which were unacceptable.For all strains as a whole,the results were consistent with those of the resistant ones.Conclusion Under the current sample size,none of the five methods met the acceptable standards,especially not suitable for the recheck of strains with higher MICs.Commercial broth dilution method have the highest consistency with MTS,and it is worth expanding the sample size for further study.

Isavuconazole represents a novel gen-eration of triazole antifungal agents for the treat-ment of invasive trichothecenes in adults.The phar-macokinetic profile of isavuconazole differs in spe-cial populations,including children,patients with ex-tracorporeal membrane oxygenation,those with he-patic or renal injury,patients undergoing blood puri-fication,and critically ill individuals and solid organ transplant recipients.These differences impact the safety and efficacy of patient treatment.This article presents the latest progress in the pharmacokinetic study of isavuconazole in these special populations.

Objective:To identify genetic etiology of ischemic stroke(IS)based on pleiotropy of obe-sity related genes.Methods:A discordant sib-pair study was designed based on the Fangshan family co-hort in Beijing.Body mass index(BMI)polygenic risk score(PRS)was first constructed under different P values.Using the polygenic transmission disequilibrium test(pTDT),we then compared the actual BMI genetic risk of siblings with IS to their expected risk,to analyze whether higher BMI was over-trans-mitted to siblings with IS.The single nucleotide polymorphism(SNP)that comprised the PRS over-trans-mitted with IS and that corresponded to the highest heritability of IS were identified as a pleiotropy SNPs set between BMI and IS.This set was then utilized as a candidate set to identify and verify risk SNPs as-so-ciated IS by transmission disequilibrium test.Finally,we identified independent genomic risk loci and mapped to genes,we then explored the biological function of the identified risk loci and genes by func-tional annotation and pathway enrichment.Results:A total of 541 participants were enrolled,with an average age of(58.4±8.1)years,including 326 discordant sib pairs of ischemic stroke.Compared with non-IS participants,IS participants with males,education level below junior high school,hypertension and hyperlipidemia accounted for a higher proportion(P＜0.05).For all the BMI PRS,we found that the actual genetic risk of BMI in siblings with IS was higher than their expectation,suggesting that genetic risk associated with high BMI was over-transmitted with IS.Compared with other SNP sets,the set(P＜5 × 10-4)corresponded to the best analytical statistics of pTDT and the highest heritability of IS and was identified as the pleiotropy SNP set between BMI and IS.Within this set,there were 45 SNPs having linkage and association with IS,which were located in 43 independent genomic risk loci and mapped to 40 genes.These genes were significantly enriched in the lipid metabolism pathway.The rs2232852 cor-rected by multiple tests was mapped to CYB5R1 and ADIPOR1,which were related to lipid metabolism and the ferroptosis pathway.Conclusion:Pleiotropy between BMI-related genes and IS was observed.Forty-five SNPs were found with linkage and association with IS in the pleiotropy gene set and mapped to 40 genes,which were functionally enriched in lipid metabolic pathways.The rs2232852 corrected by multiple tests during association analysis validation was mapped to CYB5R1 and ADIPOR1,which were related to lipid metabolism and the ferroptosis pathway,suggesting that lipid metabolism and ferroptosis played an important role in the development of IS.