With the development of artificial intelligence and big data,indirect methods for establishing ref-erence intervals(RIs)are commonly used for special populations and special forms of RIs,including continu-ous RIs,personalized RIs,and universal RIs.This paper introduces the differences and application progress of indirect RIs algorithms based on TMC,refineR,Hoffmann,Bhattacharya,Kosmic,and provides references for indirect RIs and related clinical decisions.

Objective To investigate the relationship between metaphor comprehension and theory of mind in school-aged children with autism spectrum disorder(ASD).Methods A total of 50 children with ASD(ASD group)and 50 age-and gender-matched typically developing(TD)chil-dren(TD group)were recruited from special education institutions in Hangzhou between August,2023 and No-vember,2024.Metaphor comprehension was assessed using a visual picture paradigm,covering conceptual,shape,appearance and mixed metaphors.The theory of mind was assessed using unexpected content/place tasks.Results The total score of metaphor comprehension was lower in ASD group than in TD group(Z=-5.625,P<0.001),particularly for shape,appearance and mixed metaphors(|Z|>5.625,P<0.01);as well as the scores of theory of mind(|Z|>5.255,P<0.001).There was positive correlation between the total score of theory of mind and total score(r=0.352,P<0.05),shape score(r=0.299,P<0.05)and mixed score(r=0.330,P<0.05)of metaphor comprehension.Regression analyses showed that the total score of theory of mind positively predicted total score(β=0.310,P<0.05),shape score(β=0.103,P<0.05)and mixed score(β=0.330,P<0.05)of metaphor com-prehension.Conclusion Children with ASD delayed in metaphor comprehension,which associates with deficits in theory of mind.

Objective Auditory brainstem response(ABR)is an objective electrophysiological test that evalu-ates a patient's hearing,and the ABR is interpreted primarily by recognizing the latency of waves Ⅰ through Ⅴ.The latency of wave Ⅰ to wave Ⅴ has important reference value for clinicians to judge the status of patients' auditory neu-ral pathways,so accurate interpretation of the results of this examination is particularly important.However,the a-nalysis of the result of the ABR entirely depends on the auditory teacher's ability to recognize and interpret the hu-man eye,which makes it difficult for inexperienced auditory teachers to interpret ABR waveforms.In order to solve this problem,many scholars proposed to use machine learning(ML)model to objectively interpret ABR results.ML has strong learning ability and can independently complete an objective and accurate interpretation of ABR re-sults,which brings the dawn for the objective and accurate interpretation of ABR results.

Objective To investigate the blood lipid levels in the population undergoing physical check-up population in Hangzhou dis-trict using the laboratory Big Data for providing references in disease prevention.Methods The test results of blood lipid levels of the individuals undergoing health check-up at a certain hospital from January 2022 to October 2023 were collected,excluding the abnormal positive resultss.SPSS 25.0 software was used to calculate the median(M),25th percentile(P25)and 75 Percentile(P75)grouped by gender and age in 10-year intervals.TMC was used to calculate 2.5th percentile(P25)and 97.5th percentile(P97 5),and GAMLSS was used to draw the age-continuous percentile charts.Results Gender differences in blood lipid levels were observed.The levels of total cholesterol(TC),triglycerides(TG),and low-density lipoprotein cholesterol(LDL-C)in males were higher than those of fe-males in the age of 19 to 49 groups.However,the levels of TC and LDL-C in females were higher than those of males in the age of 50 to 90 groups.TG levels in females were higher than those of males in the age of 60 to 90 groups.High-density lipoprotein cholesterol(HDL-C)levels in females were higher than those in males.TG level in males at ages of 40 to 49 reached peak,while females reached the peak of TG level at ages of 70 to 79.The LDL-C level in males at ages 40 to 49 reached the peak,while females reached the peak of LDL-C level at ages 60 to 69.Blood lipid levels were associated with age.The levels of TG,TC in female and LDL-C in female showed particularly significant changes,first increasing and then decreasing with age.Conclusion Blood lipid levels are closely relat-ed to gender and age.Personalized lipid management should be conducted,considering the factors of gender and age.

Objective This study aimed to investigate the effects of sleep interruption(SI)cycles on emotional behavior in ICR mice,and to establish a mouse model of comorbid anxiety and depression induced by SI.Methods Seventy-two male ICR mice(4～5 weeks old)were divided randomly into a blank group and a model group.Mice in the model group were subjected to SI stress modeling for 1,2,and 3 weeks,respectively.After modeling,emotional behaviors were evaluated using open-field,elevated plus maze,light-dark box,marble-burying,and forced-swimming tests.Serum corticosterone levels were detected by enzyme-linked immunosorbent assay.Results Mice in the model group buried significantly more marbles after 1 week of SI stress,compared with the blank group(P＜0.05).After 2 weeks of stress,mice in the model group also showed a significant decrease in the number of crossings in the light-dark box(P＜0.05)and a significant increase in the number of marbles buried(P＜0.01)compared with the control group.After 3 weeks of stress,mice in the model group showed a significant increase in the number of marbles buried(P＜0.05),a significant decrease in the number of crossings in the light-dark box(P＜0.05),and a significant increase in immobility time in the forced-swim test(P＜0.01).Conclusions ICR mice exhibited significant anxiety-related behaviors after 2 weeks of SI modeling and significant anxiety-and depressive-related behavioral changes after 3 weeks.Three weeks of SI stress can be used to establish a model of comorbid anxiety and depression.

Objective This study aimed to investigate the effects of sleep interruption(SI)cycles on emotional behavior in ICR mice,and to establish a mouse model of comorbid anxiety and depression induced by SI.Methods Seventy-two male ICR mice(4～5 weeks old)were divided randomly into a blank group and a model group.Mice in the model group were subjected to SI stress modeling for 1,2,and 3 weeks,respectively.After modeling,emotional behaviors were evaluated using open-field,elevated plus maze,light-dark box,marble-burying,and forced-swimming tests.Serum corticosterone levels were detected by enzyme-linked immunosorbent assay.Results Mice in the model group buried significantly more marbles after 1 week of SI stress,compared with the blank group(P＜0.05).After 2 weeks of stress,mice in the model group also showed a significant decrease in the number of crossings in the light-dark box(P＜0.05)and a significant increase in the number of marbles buried(P＜0.01)compared with the control group.After 3 weeks of stress,mice in the model group showed a significant increase in the number of marbles buried(P＜0.05),a significant decrease in the number of crossings in the light-dark box(P＜0.05),and a significant increase in immobility time in the forced-swim test(P＜0.01).Conclusions ICR mice exhibited significant anxiety-related behaviors after 2 weeks of SI modeling and significant anxiety-and depressive-related behavioral changes after 3 weeks.Three weeks of SI stress can be used to establish a model of comorbid anxiety and depression.

Tumor is the main lethal type of major diseases that human beings are facing nowadays.Traditional therapies,such as chemotherapy,surgery,radiotherapy,etc,have been the mainstay of tumor treatment for a long time,and still have their own limitations in terms of effectiveness.In recent years,immunotherapy for tumors has attracted much attention with the rise of strategies such as immune checkpoint inhibitors,chimeric antigen receptor T-cell(CAR-T)relay therapy,and anti-tumor vaccines.Among them,CAR-T cell therapy,as a breakthrough tumor immunotherapy method,can precisely target tumors at the cellular and molecular levels by modifying the patient's own T cells to express recombinant antigen receptors targeting specific tumor antigens,breaking the restriction of the major histocompatibility complex(MHC)of the natural T cells themselves.It can precisely target tumors at the cellular and molecular levels,and thus can efficiently and specifically identify and kill cancer cells,providing a new perspective for treatment.Since the approval of the first CAR-T therapy by the US Food and Drug Administration(FDA)in 2017,in addition to still maintaining significant advantages in the field of classical multiple hematologic malignancies,it has also made outstanding progress in the treatment and clinical trials of some solid tumors and autoimmune diseases,among others.This paper will briefly review the current principles,applications,challenges and directions of development of CAR-T technology.

Objective To investigate the types and mechanisms of microglial cell death induced by interaction between palmitic acid(PA)and lipopolysaccharide(LPS).Methods BV-2 microglial cells were divided into three groups for apoptosis research,BSA group,PA treatment group,and staurosporine(STA)group.They were further divided into four groups for necrosis research,BSA group,BSA+inhibitor group,PA group,and PA+inhibitor group.Western blotting was conducted to assess the expression levels of key proteins involved in apoptosis and necrosis pathways.The effect of PA on microglial cells was validated through feeding a high-fat diet to Institute of Cancer Research(ICR)mice.Results Apoptotic microglia were observed in both BSA group and PA group,PA significantly induced the activation of caspase-3,caspase-7,and poly ADP-ribose polymerase(PARP).However,compared to the BSA group,the level of activated Caspase-7 in the STA group did not change significantly.Inhibition of ferroptosis,necroptosis,or autophagy did not protect against PA-induced cell damage,while the Caspase-11 inhibitor,wedelolactone(WE),significantly improved PA induced cell damage.This study also found that PA could promote LPS entry into microglial cells and induce pyroptosis.This phenomenon and the protective effect of WE were further confirmed in a high-fat diet mouse model through immunofluorescent staining and Western blotting.Conclusion PA induces apoptosis and pyroptosis in microglial cells,while simultaneously promoting LPS entry into microglial cells and inducing pyroptosis.

Objective Auditory brainstem response(ABR)is an objective electrophysiological test that evalu-ates a patient's hearing,and the ABR is interpreted primarily by recognizing the latency of waves Ⅰ through Ⅴ.The latency of wave Ⅰ to wave Ⅴ has important reference value for clinicians to judge the status of patients' auditory neu-ral pathways,so accurate interpretation of the results of this examination is particularly important.However,the a-nalysis of the result of the ABR entirely depends on the auditory teacher's ability to recognize and interpret the hu-man eye,which makes it difficult for inexperienced auditory teachers to interpret ABR waveforms.In order to solve this problem,many scholars proposed to use machine learning(ML)model to objectively interpret ABR results.ML has strong learning ability and can independently complete an objective and accurate interpretation of ABR re-sults,which brings the dawn for the objective and accurate interpretation of ABR results.

Objective:To investigate the factors influencing sound localization in patients with unilateral sudden sensorineural hearing loss, so as to provide the reference for hearing rehabilitation of patients with unilateral sudden hearing loss.Methods:This study was a cross-sectional study that retrospectively analyzed the clinical data and audiological examination results of 228 patients with unilateral sudden sensorineural hearing loss(103 males and 125 females; aged from 18 to 80 years, with an average age of 46.2 years; 107 cases in the left ear and 121 cases in the right ear; 8 cases of low-frequency decline type, 42 cases of high-frequency decline type, 92 cases of flat decline type, and 86 cases of total deafness type)at the Eye and ENT Hospital of Fudan University from June 2023 to April 2024. The minimum audible angle (MAA) was calculated by the angle discrimination test of 1000 Hz and 4000 Hz warble tones, which were recorded as MAA 1 000 and MAA 4 000 according to the frequency of the given sound stimulus. The root mean square error (RMSE) was calculated by the angle recognition test with daily natural sounds as the stimulus sound. Using SPSS 27.0 statistical software, correlation and multiple regression analysis were used to research the clinical factors affecting the ability of sound localization in patients with unilateral sudden sensorineural hearing loss. Results:The mean MAA 1 000, MAA 4 000, RMSE of patients with unilateral sudden deafness were (53.97±29.14)°, (46.34±28.87)° and (30.06±13.64)°, respectively. Univariate analysis of variance revealed that there were significant differences between different classifications of sudden sensorineural hearing loss for sound localization tests (MAA 1 000: F=6.338, P<0.001,MAA 4 000: F=14.334, P<0.001,RMSE: F=49.918, P<0.001), post-hoc analysis observed that all significant contrasts were included the type of total deafness and low-frequency deafness. Correlation analysis showed the age of subjects in this study was weak positively correlated to the MAA 1 000 ( r=0.165, P=0.013), the duration of sudden sensorineural hearing loss was weak negatively related to RMSE ( r=-0.144, P=0.030), there were significant positive relationships between the threshold of PTA, PTA 1kHz, PTA 4kHz for the affected side, as well as the binaural PTA difference and sound localization test (MAA 1 000,MAA 4 000,RMSE) (all P<0.001). The multiple regression analysis showed the age and the binaural PTA difference for the affected side were the significant factors for the MAA 1 000 and MAA 4 000, the binaural PTA difference was the significant factors for the RMSE. The R 2 of multivariable linear regression model for MAA 1 000, MAA 4 000 and RMSE results in unilateral sudden deafness patients were 0.149, 0.207 and 0.553, respectively. Conclusion:Age, the hearing of the affected side, and binaural PTA difference are the significant factors for sound localization ability in patients with unilateral sudden sensorineural hearing loss, hearing compensation of the affected ear for these patients is hopeful to enhance the sound localization ability.