Objective To study the application of CE-Chirp in the evaluation of hearing impairment in forensic medicine by testing the auditory brainstem response(ABR)in adults using CE-Chirp to ana-lyze the relationship between the V-wave response threshold of CE-Chirp ABR test and the pure tone hearing threshold.Methods Subjects(aged 20-77 with a total of 100 ears)who underwent CE-Chirp ABR test in Changzhou De'an Hospital from January 2018 to June 2019 were selected to obtain the V-wave response threshold,and pure tone air conduction hearing threshold tests were conducted at 0.5,1.0,2.0 and 4.0 kHz,respectively,to obtain pure tone listening threshold.The differences and statistical differences between the average pure tone hearing threshold and V-wave response threshold were compared in different hearing levels and different age groups.The correlation,differences and statistical differences between the two tests at each frequency were analyzed for all subjects.The lin-ear regression equation for estimating pure tone hearing threshold for all subjects CE-Chirp ABR V-wave response threshold was established,and the feasibility of the equation was tested.Results There was no statistical significance in the CE-Chirp ABR response threshold and pure tone hearing threshold dif-ference between different hearing level groups and different age groups(P>0.05).There was a good correlation between adult CE-Chirp ABR V-wave response threshold and pure tone hearing threshold with statistical significance(P<0.05),and linear regression analysis showed a significant linear correla-tion between the two(P<0.05).Conclusion The use of CE-Chirp ABR V-wave response threshold can be used to evaluate subjects'pure tone hearing threshold under certain conditions,and can be used as an audiological test method for forensic hearing impairment assessment.

Lower-cost genotyping technology has promoted the generation of large genetic datasets with the evolving next-generation sequencing technology. The emergence of genome-wide association studies (GWAS) has facilitated researchers’ understanding of common complex diseases. GWAS refers to finding the sequence variations present in the human genome and screening out disease-related single nucleotide polymorphisms (SNPs). These SNPs are considered as the basis for assessing the stability of complex diseases. However, a single variation is not sufficient to assess an individual’s risk of disease. Polygenic risk score (PRS) is an emerging genetic data analysis method for quantitatively estimating an individual’s genetic risk for complex diseases by comprehensively considering multiple genetic variation sites. A single-value estimate of an individual’s genetic risk for a certain phenotype can be calculated as the cumulative impact of multiple genetic variants by building a PRS model. The finally expected risk score is weighted by the strength and direction of association of each SNP with the phenotype based on the number of alleles carried by each SNP. With the continuous development of various PRS calculation methods and the constant accumulation of genomic data, PRS has received widespread attention in the field of genetics. So far, quite a few studies at home and abroad have shown that PRS is valuable in risk prediction of different types of human traits or complex diseases, and its effectiveness has been further verified in clinical applications. At present, many studies have established PRS models based on GWAS summary statistics to quantify the genetic risk of susceptibility loci and clinical characteristics on diseases such as lung cancer, breast cancer, coronary heart disease, diabetes and Alzheimer’s disease. The disease-susceptible populations can be recognized through comparing the relative risk and absolute risk of the disease in different risk groups according to the population risk stratification results. Additionally, individual-level genotype data and omics data can also be used as data sources for PRS analysis research, especially the latter can dynamically reflect the short-term or long-term effects of environmental factors on human gene expression, and has potential application value in building early warning models to assess health risks. Since the calculation of PRS involves a large amount of genomic data analysis, there are big differences in the methods for data selection, model building and validation. Different PRS construction methods and software have different performances in disease risk prediction, and even the performance of same algorithm varies across diseases. It is worth noting that the PRS model often needs to be re-evaluated and verified for different groups of people, because PRS is affected by race and region. This review combines currently published PRS-related research and algorithms to describe the basic principles of PRS, compares their construction and verification methods, and discusses their applications and prospects. As a powerful genetic risk assessment tool, PRS has great potential in analyzing the genetic code of complex diseases and achieving precise diagnosis and personalized treatment.

Objective To investigate the environmental contamination related to first patient with carbapenem-re-sistant Acinetobacter baumannii(CRAB)infection and the infection status of relevant patients in a newly established intensive care unit(ICU)of a hospital in Tibetan area,and analyze the transmission risk.Methods From the ad-mission in ICU of a patients who was first detected CRAB on November 15,2021 to the 60th day of hospitalization,all patients who stayed in ICU for＞48 hours were performed active screening on CRAB.On the 30th day and 60th day of the admission to the ICU of the first CRAB-infected patient,environment specimens were taken respectively 2 hours after high-frequency diagnostic and therapeutic activities but before disinfection,and after disinfection but before medical activities.CRAB was cultured with chromogenic culture medium.Results Among the 13 patients who were actively screened,1 case was CRAB positive,he was transferred from the ICU of a tertiary hospital to the ICU of this hospital on November 19th.On the 40th day of admission to the ICU,he had fever,increased frequency for sputum suction,and CRAB was detected.The drug sensitivity spectrum was similar to that of the first case,and he also stayed in the adjacent bed of the first case.64 environmental specimens were taken,and 9 were positive for CRAB,with a positive rate of 14.06％,8 sampling points such as the washbasin,door handle and bed rail were positive for CRAB after high-frequency diagnostic and therapeutic activities.After routine disinfection,CRAB was detected from the sink of the washbasin.Conclusion For the prevention and control of CRAB in the basic-level ICU in ethnic areas,it is feasible to conduct risk assessment on admitted patients and adopt bundled prevention and con-trol measures for high-risk patients upon admission.Attention should be paid to the contaminated areas(such as washbasin,door handle,and bed rail)as well as the effectiveness of disinfection of sink of washbasin.

Objective To investigate the expression of essential meiotic endonuclease 1(EME1)in liver cancer tissue and its effect on the biological behavior of hepatoma cells.Methods The TCGA database was used to identify the differentially expressed genes between liver cancer tissue and paracancerous tissue.Immunohistochemistry and Western Blot were used to measure the expression abundance of EME1 in liver cancer tissue.A lentivirus was constructed by short hairpin RNA,and BEL-7404 cells were transfected with the lentivirus to interfere with the expression of the EME1 gene;the cells were divided into silencing group(shEME1 group)and control group(shCtrl group).Quantitative real-time PCR and Western Blot were used to measure the mRNA and protein expression levels of EME1;Celigo Image Cytometer and MTT assay were used to measure cell proliferation rate;flow cytometry was used to observe cell cycle;Caspase 3/7 activity was used to measure cell apoptosis.The independent-samples t-test was used for comparison between two groups.Results TCGA results showed that the mRNA expression level of EME1 in liver cancer tissue was 18.9 times that in paracancerous tissue(t=5.00,P<0.001),and the protein expression level of EME1 in liver cancer tissue was 7.0 times(based on immunohistochemistry:8.4±2.6 vs 1.2±0.4,t=7.55,P<0.001)or 2.5 times(based on Western Blot:249.0%±35.5%vs 100.0%±77.8%,t=3.02,P<0.05)that in paracancerous tissue.After lentivirus infection,compared with the shCtrl group,the shEME1 group had an mRNA expression level of EME1 reduced by 29.9%(29.9%±0.9%vs 100.0%±3.6%,t=32.82,P<0.001),a protein expression level of EME1 reduced by 35.7%(35.7%±14.9%vs 100.0%±28.9%,t=3.42,P<0.05),and a level of cell counting reduced by 45.1%(4 053±167 vs 8 988±477,t=16.91,P<0.001),as well as a level of cell activity reduced to 66.9%(0.518±0.046 vs 0.774±0.022,t=8.74,P<0.001)and a level of colony forming ability reduced to 29.0%(75±6 vs 260±9,t=28.92,P<0.001).Compared with the shCtrl group,the shEME1 group had a significant increase in the proportion of cells in G1 phase(49.9%vs 44.0%,t=8.96,P<0.001)and significant reductions in the proportion of cells in G2/M phase(15.9%vs 17.9%,t=9.13,P<0.001)and S phase(34.2%vs 38.1%,t=6.91,P<0.001),while Caspase 3/7 activity was enhanced by 1.5 times(145.8%±5.9%vs 100.0%±2.3%,t=12.50,P<0.001).Conclusion EME1 is highly expressed in liver cancer tissue,and silencing the EME1 gene can inhibit the proliferation of hepatoma cells and promote cell apoptosis.

Objective To investigate the role of bone marrow mesenchymal stem cells derived from diabetic mice and their paracrine roles in inducing insulin resistance(IR).Methods The mouse model of diabetes mellitus was established,bone marrow mesenchymal stem cells(BMSC)were extracted and cultured,and the culture supernatant(M-BMSC-CS)was collected.(1)Cell experiment:HepG2 hepatocytes were divided into normal low-glycemic culture group[cultured with low-glycemic DMEM(5.55 mmol·L-1)],M-BMSC-CS experimental group(M-BMSC-CS 75 μL),and high-glycemic and high-lipid control group(given 25 mmol·L-1 high-glycemic DMEM+0.25 mmol·L-1 palmitic acid);(2)Animal experiments:Mice were divided into normal mice group(0.9％NaCl by intraperitoneal injection)and M-BMSC-CS-m group(M-BMSC-CS by intraperitoneal injection of normal mice(injection dose 0.2 mL/10 g)].Glucose intake was measured by glucose oxidase method.The fluorescence intensity of Glut2 protein was detected by immunofluorescence.The expression of insulin signaling pathway protein was detected by Western blot.Test oral glucose tolerance(OGTT)and insulin tolerance(ITT).Results The glucose intakes of the normal low-glucose culture group,the M-BMSC-CS experimental group and the high-glucose and high-lipid control group were(2.96±0.05),(1.64±0.28)and(1.42±0.32)mmol·L-1,respectively;the fluorescence expressions of glucose transporter 2(Glut2)were 53.21±2.70,30.95±3.39 and 34.96±7.60,respectively;the protein expression levels of phosphorylated insulin receptor substrate 1-ser307(p-IRS-1ser307)were 0.46±0.21,1.09±0.24 and 0.91±0.16,respectively;phosphorylated protein kinase(p-AKT)protein expression levels were 0.94±0.05,0.59±0.06 and 0.53±0.05;Glut2 protein expression levels were 1.08±0.14,0.58±0.14 and 0.62±0.09,respectively.The above indexes in M-BMSC-CS experimental group were statistically significant compared with those in normal low-glycemic culture group(all P＜0.05).Fasting blood glucose levels in the normal group and M-BMSC-CS-m group were(5.23±0.57)and(9.30±1.14)mmol·L-1;p-AKT protein expression level were 1.27±0.21 and 0.51±0.19;Glut2 protein expression level were 1.17±0.17 and 0.79±0.09,respectively.The above indexes in M-BMSC-CS-m group were significantly different from those in normal mouse group(P＜0.05).Conclusion BMSC culture supernatant from diabetic mice induced insulin resistance of normal HepG2 hepatocytes in vitro and normal mice in vivo.

Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.

Objective To elucidate the clinical significance of high expression levels of endonuclease meiosis 1(EME1)in the prognosis of hepatocellular carcinoma(HCC).Methods The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases were used to screen and analyze differential gene expression between HCC and non-tumor tissues.A retrospective collection of liver tissue samples from 80 HCC patients who underwent hepatectomy in the Fifth Medical Center of Chinese PLA General Hospital between January 2010 and December 2014 was performed.Immunohistochemistry analysis was employed to detect the EME1 expression levels.Survival analysis was then conducted to assess the impact of EME1 expression on 5-year postoperative survival rate of HCC patients.Additionally,gene enrichment analysis was applied to predict the function of EME1 in HCC.Results A total of 371 HCC tissue samples and 50 non-tumor liver tissue samples from TCGA database were analyzed,revealing significantly higher EME1 expression in HCC tissues.Microarray analysis of 107 samples within the GEO database(70 HCC tissues and 37 non-tumor tissues)confirmed that EME1 mRNA expression was markedly elevated in HCC tissues compared with non-tumor tissues(P<0.05).The 5-year overall survival(OS)rate was notably lower in high EME1 expression group than that in low expression group(44.1%vs.53.0%,P<0.05).Semi-quantitative immunohistochemistry analysis demonstrated that patients with high EME1 expression had a significantly lower OS rate than those with low EME1 expression(32.8%vs.45.0%,P<0.05).Multivariate COX regression analysis identified that high EME1 expression(HR=2.234,95%CI 1.073-4.649,P=0.032)and advanced China liver caner(CNLC)staging(HR=4.317,95%CI 1.799-10.359,P=0.001)were independent risk factors for the 5-year OS of post-operation patients with HCC.Conclusion Elevated EME1 expression in HCC tissues correlates with an adverse prognosis of HCC and suggests that EME1 could serve as a potential therapeutic target for HCC.

Purpose::To explore the effect of green channel for stroke patients on the treatment of severe aneurysmal subarachnoid hemorrhage.Methods::This is a retrospective case-control study. The clinical data of patients with severe aneurysmal subarachnoid hemorrhage admitted to the emergency department of our hospital from January 2015 to June 2022 were retrospectively analyzed. Patients diagnosed with subarachnoid hemorrhage, confirmed intracranial aneurysm by preoperative CT angiography or digital subtraction, graded Hunt-Hess grade III, IV, and V, < 72 h from the onset to the time of consultation received surgical treatment in our hospital were included in this study. Patients with serious underlying diseases, such as heart, liver, kidney diseases, or malignant tumors, traumatic subarachnoid hemorrhage, previous history of cerebral hemorrhage, and incomplete data were excluded. The control group included patients with severe aneurysmal subarachnoid hemorrhage admitted from January 2015 to December 2018 before the establishment of the green channel for stroke patients, and the observation group included patients with severe aneurysmal subarachnoid hemorrhage admitted from January 2019 to June 2022 after the establishment of the green channel. The control group received routine treatment in the emergency department; the observation group received improved treatment of green channel for stroke patients. Gender, age, Hunt-Hess grade on admission, modified Rankin scale (mRS) on admission, aneurysm location, aneurysm size and whether accompanied by intracerebral hemorrhage, the time from onset to emergency department, the time from emergency department to vascular diagnostic examination, the time from onset to surgery, the time from emergency department to surgery, the time from hospital admission to surgery, length of hospital stay, complications, treatment effect were analyzed and compared between the 2 groups. SPSS 23.0 software was utilized to conduct comparisons between the 2 groups. The t-test, Chi-square test, or Mann-Whitney U test was chosen based on the data type. Statistical significance was established when p < 0.05. Results::A total of 71 patients were included in this study, of whom 37 were in the control group and 34 were in the observation group. There were no statistical differences in age, gender, Hunt-Hess grade, mRS scores, aneurysm location, aneurysm size, intracerebral hemorrhage, the time from onset to emergency department, length of hospital stay, complications between the observation group and the control group (all p > 0.05). The time (min) from visit to vascular diagnostic test (60.50 vs. 120.00, p =0.027), the time (min) from onset to surgery (1792.00 vs. 2868.00, p =0.023), the time (min) from emergency department to surgery (1568.50 vs. 2778.00, p =0.016), the time (min) from hospital admission to surgery (1188.50 vs. 2708.00, p =0.043), all of them were shorter in the observation group than those in the control group. The relative values of admission and 7-day postoperative mRS scores and the relative values of admission and discharge mRS scores ≥ 2 were used as the criteria for determining better efficacy, and the treatment effect was better than that in the control group, and the differences were statistically significant (admission to 7 days postoperative mRS score ≥ 2, 17 (50.0 %) vs. 8 (21.6 %), p =0.012; admission to discharge mRS score ≥ 2, 19 (55.9 %) vs. 11 (29.7 %), p =0.026). Conclusion::The green channel for stroke patients with severe aneurysmal subarachnoid hemorrhage can effectively shorten the time from arrival at the emergency department to vascular diagnostic examination and the time from the emergency department to surgery, and achieve a better therapeutic effect, which is worth popularizing and applying.

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates.Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity.This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes.The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes,and corresponding reference ranges will be established.The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance,with altitude gradients divided into 4 categories:800 m,1 900 m,2 400 m,and 3 500 m,with an anticipated sample size of 170 neonates per altitude gradient.This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.[Chinese Journal of Contemporary Pediatrics,2024,26(4):403-409]

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.