Objective To mine and conduct comparative analysis for hepatic dysfunction adverse events of voriconazole and other antifungal drugs,based on the Food and Drug Administration Adverse Event Reporting System(FAERS)database,and provide reference for clinical practice.Methods Data from January 2004 to March 2022 in FAERS were retrieved.We estimate the association between the hepatic dysfunction events and voriconazole using reporting odds ratio(ROR)for mining the adverse drug event report signals and compare voriconazole with the full database and other antifungal drugs.Results A total of 646 reports of hepatic dysfunction related to voriconazole as the primary suspect drug were collected totally.The median time to event of the hepatic dysfunction events was 8 d.The overall ROR 95％confidence interval(CI)for hepatic-related adverse drug events was 6.82(95％CI=6.26-7.42).Comparing to other antifungal drugs,voriconazole significantly increased the risk of hepatic dysfunction compared with fluconazole,isavuconazole and amphotericin B,with RORs of 2.19(95％CI=1.94-2.47),2.31(95％CI=1.66-3.22)and 1.26(95％CI=1.08-1.48).The top 10 adverse event signals are cholestasis,hepatic cytolysis,mixed liver injury,hepatitis cholestatic,blood alkaline phosphatase increased,γ-glutamyltransferase increased,hepatic function abnormal,hepatocellular injury,liver function test abnormal and hepatosplenomegaly,and all of them have great correlation with voriconazole(ROR＞5).Conclusion Voriconazole is closely related to hepatic dysfunction,indicating that clinical attention should be paid to patients'hepatic function indicators during medication.Since the risk of hepatic dysfunction caused by voriconazole depends on several factors including the underlying disease of the patient and the exposure level of the drugs,close clinical and laboratory monitoring,including therapeutic drug monitoring,are essential to prevent or promptly recognize further deterioration of the hepatic function.

Objective To explore the effect and mechanism of hawthorn leaves flavonoids(HLF)on angiotensin Ⅱ(Ang Ⅱ)-induced myocardial hypertrophy.Methods The H9c2 cells were divided into control group(normal culture),model group(100 nmol·L-1 Ang Ⅱ for 24 h),experimental-L,-M,-H groups(received 100 nmol·L-1 Ang Ⅱ for 24 h,then treated with 25,50 and 100 mg·L-1 HLF for 24 h,respectively),anti-miR-NC and anti-miR-21a-5p groups(transfected with anti-miR-NC and anti-miR-21a-5p,then treated with 100 nmol·L-1 Ang Ⅱ for 24 h),miR-NC+high-dose and miR-21a-5p+high-dose group(transfected with miR-NC and miR-21a-5p mimics,then treated with 100 nmol·L-1 Ang Ⅱ for 24 h+100 mg·L-1 HLF for 24 h).The cell viability was detected by cell counting kit-8.The cell apoptosis was measured by flow cytometry.The expression levels of miR-21a-5p was assessed by quantitative real-time polymerase chain reaction.The expression levels of cyclooxygenase-2(COX2)and prostaglandin E2(PGE2)was measured by Western blot.Results The cell viabilities of control,model group experimental-H groups were 1.03±0.09,0.51±0.05 and 0.93±0.08;cell apoptosis rates were(7.69±0.61)％,(23.04±1.82)％and(9.43±0.71)％;the expression levels of miR-21a-5p were 1.00±0.09,2.43±0.18 and 1.09±0.08;the relative expression levels of COX2 protein were 0.42±0.03,0.85±0.08 and 0.40±0.04;the relative expression levels of PGE2 protein were 0.34±0.03,0.75±0.07 and 0.35±0.03;the differences of above indexes were statistically significant between the model group and the control and experimental-H groups(all P＜0.05).The cell viabilities of anti-miR-NC,anti-miR-21a-5p,miR-NC+high dose and miR-21a-5p+high dose groups were 0.52±0.04,1.12±0.08,0.94±0.09 and 0.57±0.04;the cell apoptosis rates were(23.04±1.82)％,(9.86±0.73)％,(9.47±0.64)％and(24.96±1.94)％;the expression levels of miR-21a-5p were 1.00±0.10,0.43±0.04,1.00±0.09 and 2.12±0.18;the relative expression levels of COX2 protein were 0.86±0.05,0.39±0.04,0.41±0.03 and 0.78±0.07;the relative expression levels of PGE2 protein were 0.74±0.06,0.38±0.07,0.36±0.02 and 0.71±0.05.Compared the anti-miR-21a-5p group with the anti-miR-NC group,compared the miR-21a-5p+high-dose group with the miR-NC+high-dose group,the differences of above indexes were statistically significant(all P＜0.05).Conclusion HLF can inhibit Ang Ⅱ-induced myocardial hypertrophy by regulating the expression of miR-21a-5p and COX2/PGE2 pathway.

Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal microbiota. Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq. Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336-0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide metabolism.Additionally,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34-0.55),which were mainly involved in neurodevelopment. Conclusion Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.

Objective To analyze the influencing factors for catheter-associated infection(CAI)in chemotherapy treated patients after indwelling peripherally inserted central catheter(PICC)based on a random forest model.Methods 400 tumor patients who received chemotherapy and PICC were selected and divided into the training set(n=300)and the test set(n=100)in a 3∶1 ratio through computer-generated random number.Patients in the training set were subdivided into the non-infection group and the infection group based on the occurrence of infec-tion.Clinical data from two groups of patients were compared.Influencing factors for the occurrence of CAI after PICC were analyzed with multivariate logistic regression model and the integrated classification algorithm of random forest model,and the predictive performance of the two methods was compared.Results Among 300 chemotherapy treated patients in the training set,32 cases(10.67％)experienced CAI.Compared with the non-infection group,patients in the infection group had more single punctures for catheterization,longer PICC retention time,larger pro-portion of catheter movement,larger proportion of complication with diabetes,higher frequency of dressing chan-ges,lower white blood cell count and immune function(all P＜0.05).PICC retention time,catheter movement,complication with diabetes,dressing change frequency,white blood cell(WBC)and immune function were inde-pendent influencing factors for CAI after PICC(all P＜0.05).The random forest model showed that ranking by the importance of different influencing factors was as following:PICC retention time,catheter movement,complication with diabetes,WBC,dressing change frequency and immune function.The integrated classification algorithm of random forest model for predicting the occurrence of CAI in chemotherapy treated patients showed that the area un-der the receiver operating characteristic(ROC)curve(AUC)was 0.872,which had better prediction performance compared with the logistic regression model(AUC=0.791).Conclusion PICC retention time,catheter movement,complicated with diabetes,dressing change frequency,WBC level and immune function are independent influencing factors for CAI in chemotherapy treated patients.The integrated classification algorithm of random forest model can be used to predict CAI in chemotherapy treated patients,and its prediction performance is better than that of the logistic regression model.

Based on introducing the total price adjustments in pilot cities and analyzing the existing problems,it further analyzes the objectives of the total price adjustment allocation of medical service items,the characteristics of various types of medical service items and the possible impact of price adjustment,concludes that the priority of the total price adjustment allocation should be as follows:new items,special tasks,complex items,general items,and medical services for special needs.It also combines the practical experience of the pilot cities to establish the total price adjustment allocation mechanism,and provides opinions on the total price adjustment allocation before the dynamic adjustment of medical service prices in the future.

Based on introducing the total price adjustments in pilot cities and analyzing the existing problems,it further analyzes the objectives of the total price adjustment allocation of medical service items,the characteristics of various types of medical service items and the possible impact of price adjustment,concludes that the priority of the total price adjustment allocation should be as follows:new items,special tasks,complex items,general items,and medical services for special needs.It also combines the practical experience of the pilot cities to establish the total price adjustment allocation mechanism,and provides opinions on the total price adjustment allocation before the dynamic adjustment of medical service prices in the future.

Based on introducing the total price adjustments in pilot cities and analyzing the existing problems,it further analyzes the objectives of the total price adjustment allocation of medical service items,the characteristics of various types of medical service items and the possible impact of price adjustment,concludes that the priority of the total price adjustment allocation should be as follows:new items,special tasks,complex items,general items,and medical services for special needs.It also combines the practical experience of the pilot cities to establish the total price adjustment allocation mechanism,and provides opinions on the total price adjustment allocation before the dynamic adjustment of medical service prices in the future.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To explore the current application of high-throughput drug sensitivity(HDS)testing in children with relapsed and refractory acute leukemia(RR-AL)and analyze the feasibility of salvage treatment plans.Methods A retrospective collection of clinical data from children with RR-AL who underwent HDS testing at the Department of Children's Hematology and Oncology of the First Affiliated Hospital of Zhengzhou University from November 2021 to October 2023 was conducted,followed by an analysis of drug sensitivity results and treatment outcomes.Results A total of 17 children with RR-AL underwent HDS testing,including 7 cases of relapsed refractory acute myeloid leukemia and 10 cases of relapsed refractory acute lymphoblastic leukemia.The detection rate of highly sensitive chemotherapy drugs/regimens was 53%(9/17),while the detection rate of moderately sensitive chemotherapy drugs/regimens was 100%(17/17).Among the 17 RR-AL patients with highly and moderately sensitive chemotherapy drugs and regimens,the MOACD regimen(mitoxantrone+vincristine+cytarabine+cyclophosphamide+dexamethasone)accounted for 100%,with the highest inhibition rate for single-agent mitoxantrone(94%,16/17),and the highest inhibition rate for targeted therapy being bortezomib(94%,16/17).Nine patients adjusted their chemotherapy based on HDS testing results,with 4 undergoing hematopoietic stem cell transplantation.Four patients achieved disease-free survival,while 5 died.Eight patients received empirical chemotherapy,with 2 undergoing hematopoietic stem cell transplantation;4 achieved disease-free survival,while 4 died.Conclusions HDS testing can identify highly sensitive drugs/regimens for children with RR-AL,improving the rate of re-remission and creating conditions for subsequent hematopoietic stem cell transplantation.

Objective To investigate the status of neurodevelopmental catch-up and suitable correction termination age in preterm infants of different gestational ages. Methods A total of 918 preterm infants without significant high-risk factors who attended the outpatient service of the Second Affiliated Hospital of Army Medical University from January 1,2018 to March 1,2023 were included. The data on developmental quotient (DQ) in Gesell Developmental Schedule (GDS) were collected,while 6684 full-term infants were included as controls. According to the gestational age,the infants were divided into preterm groups (early preterm,moderate preterm,and late preterm births) and a full-term group,and these groups were compared in terms of DQ of each functional area and its changing trend with 48 months of chronological age. Results The DQ values of all functional areas showed a catch-up trend from 6 months to 48 months of chronological age in each preterm group (P<0.05). There were no significant differences in the DQ values of all functional areas between the late preterm and full-term groups at the chronological age of 36 months (P>0.05). There were significant differences in the DQ values of most functional areas between the moderately/early preterm groups and the full-term group at the chronological age of 36 months (P<0.05),but no significant differences were found in the DQ values of all functions areas at the chronological age of 48 months (P>0.05). Conclusions The correction termination age for neurodevelopment in preterm infants may need to extend beyond 36 months,and the smaller the gestational age,the longer the time required for correction.