Objective To study the plasma metabolomics of mice poisoned by different dosage of the combination of diazepam and ethanol,and to reveal the toxicological mechanisms of combined poisoning of diazepam and ethanol.Methods Female Kunming mice were randomly divided into blank group,single and combined poisoning group(n=6),Based on the LD50 of diazepam co-administered with graded ethanol doses,mice in the single-drug and combined groups received oral gavage at 1/2,1,and 2 × LD50.Retro-orbital blood samples(～500 μL)were collected within 24 hours post-administration and analyzed by UPLC-QE-MS technology.Principal component analysis and orthogonal partial least squares discriminant analysis were used to identify differential metabolites and associated metabolic pathways.Results A total of 387 differential metabolites were identified in the combined poisoning group of diazepam and ethanol implicating the key pathways including tryptophan metabolism,phenylalanine metabolism,arginine and proline metabolism,Glycerophospholipid metabolism,phenylalanine,tyrosine and tryptophan biosynthesis.Conclusion Combined diazepam and ethanol poisoning exerts significant systemic effects by disrupting neurotransmitters conduction,exacerbating oxidative stress response and dysregulating energy metabolism.

Objective To establish a high-throughput non-targeted screening and prioritization method for emerging pollutants(EPs)in sewage using direct injection high-resolution mass spectrometry(HRMS).Methods The sewage samples were filtered by membrane filter and directly subjected to the liquid chromatography-time-of-flight mass spectrometer based on a method modified from our previous study.A C18 chromatographic column was applied for a gradient elution separation,and accurate mass and mass spectral fragment information were obtained through the MS full scan mode and MS/MS DIA data collection mode.After peak detection and alignment,the features from the raw data through open source software MZmine 3,and then high-throughput screening strategies such as MassBank and PubChem databases were used for compound annotation.Finally,the candidate features were confirmed with chemical standards by compared their retention time and mass spectrum fragmentation ion peaks.Results 13 EPs were identified,including 7 industrial chemicals,4 pharmaceuticals,1 pesticide and 1 metabolite.High detection rates were observed for metformin(86.2％),2-hydroxybenzothiazole(79.3％),1,2-benzisothiazole-3-one(72.4％),and 1,2-benzisothiazole-3-one(72.4％).The quantitative concentration range of EPs was 1.37～19.05 ng/mL,with the high concentrations observed for melamine(19.05 ng/mL)and furosemide(18.49 ng/mL).Ecological risk assessment identified 1,2-benzisothiazol-3-one,4-aminoacetophenone,creatinine,2-hydroxybenzothiazole,and furosemide as key pollutants.Conclusion This direct injection coupled with HRMS workflow enables efficient non-targeted screening and prioritization of emerging EPs in sewage samples,highlighting five ecotoxicologically critical EPs.The methodology enhances environmental monitoring capabilities and provide critical technical support for interdisciplinary research such as environmental forensics and health risk assessment.

Objective To investigate the value of intravoxel incoherent motion diffusion-weighted imaging(IVIM-DWI)in predicting the clinical and pathological features of prostate cancer(PCa).Methods We recruited 47 patients who underwent bpMRI combined with IVIM-DWI in our hospital from July 2022 to October 2023 and pathologically confirmed with PCa.Among these cases,20 were transitional zone PCa(TZ-PCa),and 27 were peripheral zone PCa(PZ-PCa).According to the International Society of Urological Pathology(ISUP)risk grades,the patients were divided into high-risk group(ISUP≥3)and low-risk group(ISUP≤2).Differences in the risk levels between TZ-PCa group and PZ-PCa group were compared.Factors including age,total prostate-specific antigen(tPSA),diffusion coefficient(D)value,pseudo diffusion coefficient(D*)value,perfusion fraction(F)value,and apparent diffusion coefficient(ADC)as independent variables were compared between the two groups.Binary logistic regression analysis was further used to identify the factors associated with high or low risk of PCa.Receiver operation characteristic(ROC)curves were plotted to evaluate the diagnostic efficacy of PSA,D value,anatomical zones,and the combined model of PSA+D value+anatomical zones in predicting the risk level of PCa.Results The risk level was higher in PZ-PCa group than in TZ-PCa group(P=0.015).Binary logistic regression analysis showed that the tPSA level in the high-risk group of PCa was higher than that in the low-risk group(OR=1.026,95％CI:1.004-1.049,P=0.014),but the Dmean value was lower than that in the low-risk group(OR=0.993,95％CI:0.987-0.999,P=0.034).PCa in the high-risk group was more distributed in the peripheral zone(OR=5.250,95％CI:1.468-18.772,P=0.023).The diagnostic efficacy of the combined model(AUC=0.887,95％CI:0.787-0.987)was higher than that of tPSA,Dmean,or anatomical partitioning alone(P=0.001,0.043,and 0.003,respectively).Conclusion PZ-PCa has a higher risk level than TZ-PCa.Combining bpMRI localization of anatomical zones with PSA and D value provides the highest efficacy in predicting the risk level of PCa,which can potentially support the development of precise and personalized clinical diagnosis and treatment strategies for PCa.

Objective To study the plasma metabolomics of mice poisoned by different dosage of the combination of diazepam and ethanol,and to reveal the toxicological mechanisms of combined poisoning of diazepam and ethanol.Methods Female Kunming mice were randomly divided into blank group,single and combined poisoning group(n=6),Based on the LD50 of diazepam co-administered with graded ethanol doses,mice in the single-drug and combined groups received oral gavage at 1/2,1,and 2 × LD50.Retro-orbital blood samples(～500 μL)were collected within 24 hours post-administration and analyzed by UPLC-QE-MS technology.Principal component analysis and orthogonal partial least squares discriminant analysis were used to identify differential metabolites and associated metabolic pathways.Results A total of 387 differential metabolites were identified in the combined poisoning group of diazepam and ethanol implicating the key pathways including tryptophan metabolism,phenylalanine metabolism,arginine and proline metabolism,Glycerophospholipid metabolism,phenylalanine,tyrosine and tryptophan biosynthesis.Conclusion Combined diazepam and ethanol poisoning exerts significant systemic effects by disrupting neurotransmitters conduction,exacerbating oxidative stress response and dysregulating energy metabolism.

Objective To establish a high-throughput non-targeted screening and prioritization method for emerging pollutants(EPs)in sewage using direct injection high-resolution mass spectrometry(HRMS).Methods The sewage samples were filtered by membrane filter and directly subjected to the liquid chromatography-time-of-flight mass spectrometer based on a method modified from our previous study.A C18 chromatographic column was applied for a gradient elution separation,and accurate mass and mass spectral fragment information were obtained through the MS full scan mode and MS/MS DIA data collection mode.After peak detection and alignment,the features from the raw data through open source software MZmine 3,and then high-throughput screening strategies such as MassBank and PubChem databases were used for compound annotation.Finally,the candidate features were confirmed with chemical standards by compared their retention time and mass spectrum fragmentation ion peaks.Results 13 EPs were identified,including 7 industrial chemicals,4 pharmaceuticals,1 pesticide and 1 metabolite.High detection rates were observed for metformin(86.2％),2-hydroxybenzothiazole(79.3％),1,2-benzisothiazole-3-one(72.4％),and 1,2-benzisothiazole-3-one(72.4％).The quantitative concentration range of EPs was 1.37～19.05 ng/mL,with the high concentrations observed for melamine(19.05 ng/mL)and furosemide(18.49 ng/mL).Ecological risk assessment identified 1,2-benzisothiazol-3-one,4-aminoacetophenone,creatinine,2-hydroxybenzothiazole,and furosemide as key pollutants.Conclusion This direct injection coupled with HRMS workflow enables efficient non-targeted screening and prioritization of emerging EPs in sewage samples,highlighting five ecotoxicologically critical EPs.The methodology enhances environmental monitoring capabilities and provide critical technical support for interdisciplinary research such as environmental forensics and health risk assessment.

Objective To investigate the value of intravoxel incoherent motion diffusion-weighted imaging(IVIM-DWI)in predicting the clinical and pathological features of prostate cancer(PCa).Methods We recruited 47 patients who underwent bpMRI combined with IVIM-DWI in our hospital from July 2022 to October 2023 and pathologically confirmed with PCa.Among these cases,20 were transitional zone PCa(TZ-PCa),and 27 were peripheral zone PCa(PZ-PCa).According to the International Society of Urological Pathology(ISUP)risk grades,the patients were divided into high-risk group(ISUP≥3)and low-risk group(ISUP≤2).Differences in the risk levels between TZ-PCa group and PZ-PCa group were compared.Factors including age,total prostate-specific antigen(tPSA),diffusion coefficient(D)value,pseudo diffusion coefficient(D*)value,perfusion fraction(F)value,and apparent diffusion coefficient(ADC)as independent variables were compared between the two groups.Binary logistic regression analysis was further used to identify the factors associated with high or low risk of PCa.Receiver operation characteristic(ROC)curves were plotted to evaluate the diagnostic efficacy of PSA,D value,anatomical zones,and the combined model of PSA+D value+anatomical zones in predicting the risk level of PCa.Results The risk level was higher in PZ-PCa group than in TZ-PCa group(P=0.015).Binary logistic regression analysis showed that the tPSA level in the high-risk group of PCa was higher than that in the low-risk group(OR=1.026,95％CI:1.004-1.049,P=0.014),but the Dmean value was lower than that in the low-risk group(OR=0.993,95％CI:0.987-0.999,P=0.034).PCa in the high-risk group was more distributed in the peripheral zone(OR=5.250,95％CI:1.468-18.772,P=0.023).The diagnostic efficacy of the combined model(AUC=0.887,95％CI:0.787-0.987)was higher than that of tPSA,Dmean,or anatomical partitioning alone(P=0.001,0.043,and 0.003,respectively).Conclusion PZ-PCa has a higher risk level than TZ-PCa.Combining bpMRI localization of anatomical zones with PSA and D value provides the highest efficacy in predicting the risk level of PCa,which can potentially support the development of precise and personalized clinical diagnosis and treatment strategies for PCa.

Objective:To establish the ultra-high performance liquid chromatography (UPLC) fingerprint and high performance liquid chromatography (HPLC) content determination method of Curcumae Radix standard decoction; To predict the quality markers of Curcumae Radix standard decoction combined with network pharmacology.Methods:UPLC method was used to establish the fingerprint of Curcumae Radix standard decoction, and the common peaks were determined. Combined with chemical pattern recognition techniques such as similarity analysis and clustering analysis, Curcumae Radix standard decoction from different producing areas was studied, and curcumol was used as an index to determine the content of 24 batches of Curcumae Radix standard decoction. At the same time, network pharmacology was used to predict potential of curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one.Results:A total of 24 batches of Curcumae Radix standard decoction from different habitats were compared and analyzed, and 10 common peaks were calibrated. The similarity of 24 batches of samples ranged from 0.982 to 0.999. Clustering analysis and principal component analysis divided them into three categories. Heat map analysis showed that peak 8 (curcumol) and peak 9 ((1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one) were the main components. The content of curcumol in 24 batches of Curcumae Radix standard decoction was 0.69-1.87 mg/g; curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β- (3-oxobutyl) bicyclo [4.1.0] heptan-3-one may regulate the neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation by regulating neuroactive ligand-receptor interaction signaling pathway, calcium signaling, and excitation. It was preliminarily predicted that curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one were potential quality markers of Curcumae Radix.Conclusion:Curcumol and (1S, 6β)-1β-Methyl-4-(1-methylethylidene)-7β-(3-oxobutyl) bicyclo [4.1.0] heptan-3-one are potential quality markers of Curcumae Radix standard decoction, and the established fingerprint can be used for the quality control of Curcumae Radix standard decoction.

Objective:Acoustic neuroma(AN)is a benign tumor that usually affects a patient's hearing and balance function.For the screening and diagnosis of AN,the traditional approach mainly relies on audiological examination and magnetic resonance imaging(MRI),often ignoring the importance of vestibular function assessment in the affected area.As an emerging method of vestibular function detection,video head impulse test(vHIT)has been widely used in clinic,but research on its use in AN diagnosis is relatively limited.This study aims to explore the value of vHIT in the diagnosis of AN,vestibular dysfunction assessment,and postoperative compensation establishment in unilateral AN patients undergoing unilateral AN resection through labyrinthine approach. Methods:This retrospective study was conducted on 27 AN patients who underwent unilateral AN resection via labyrinthine approach from October 2020 to March 2022 in the Department of Otolaryngology-Head and Neck Surgery,the Second Xiangya Hospital,Central South University.vHIT was performed 1 week before surgery to assess vestibular function,pure tone audiometry(PTA)was used to assess hearing level,and ear MRI was used to assess tumor size.Follow-up vHIT was conducted at 1 week,1 month,6 months,and 1 year post-surgery.The correlation of vHIT with hearing and tumor size was analyzed. Results:Preoperative vHIT showed that the posterior semicircular canal on the affected side was the most common semicircular canal with reduced vestibulo-ocular reflex(VOR)gain.There was a correlation between the VOR gain of vHIT on the affected side and the hearing level(r=-0.47,P<0.05)or tumor size(r=-0.54,P<0.01).The results of vHIT on the affected side showed that the hearing level and mean VOR gain of the anterior semicircular canal increased slightly with time,and the amplitude and saccade percentage of the dominant saccades of the 3 semicircular canals increased,while the latency time decreased,with the most obvious changes occurring 1 week post-surgery. Conclusion:vHIT can effectively monitor the changes of vestibular function in AN patients before and after surgery and has application value in assisting the diagnosis of vestibular dysfunction in AN patients.

Objective:Ménière's disease(MD)is an idiopathic inner ear disorder characterized by recurrent episodes of episodic rotational vertigo,fluctuating hearing loss,tinnitus,and a feeling of ear stuffiness.Endolymphatic sac(ES)-related surgery is used primarily in patients with MD who have failed to respond to pharmacologic therapy.Endolymphatic duct blockage(EDB)is a new procedure for the treatment of MD,and related clinical studies are still scarce.This study aims to investigate the dynamic changes in endolymphatic hydrops(EH)and the long-term surgical outcomes in MD patients undergoing EDB,and to evaluate the impact of different types of ES on the surgical efficacy. Methods:A retrospective analysis was conducted on 33 patients with refractory MD who underwent EDB.Based on the morphology of their endolymphatic sacs,patients were divided into a normal-type group(n=14)and an atrophic-type group(n=19).The frequency of vertigo symptoms,hearing,vestibular function,and the dynamic changes of gadolinium-enhanced MRI of the inner ear were compared were compared before and after surgery between the 2 groups. Results:Compared with the atrophic-type group,the patients in the normal-type group had a higher rate of complete vertigo control,better cochlear and vestibular function,and a lower endolymph to vestibule volume ratio(all P<0.05).In addition,7 patients in the normal-type group were found to have reversal of EH,while no reversal of EH was detected in the atrophic-type group after surgery. Conclusion:The response to EDB treatment varies between normal and atrophic MD patients,suggesting that the 2 pathological types of endolymphatic sacs may have different underlying mechanisms of disease.

Objective To investigate the effect of core decompression combined with bone-morphogenetic proteins(BMP)activity inducing rod implantation in the treatment of early-stage femoral head necrosis.Methods Retrospective analysis of 116 patients with early-stage femoral head necrosis from June 2018 to June 2022 were divided into core decompression combined with BMP activity inducing rod group(BMP group)and allograft bone group.Sixty cases in the BMP group were treated with core decompression combined with implantation of BMP-activated induced rods,and 56 cases in the allograft group were treated with core decompression combined with bone grafting of the allograft bone by punching and compression.The differences in hip Harris scores and visual analogue scores(VAS)of pain between the two groups at preoperative,6 months postoperative and 1 year postop-erative,and the patient treatment response and femoral head survival rate at 1 year postoperative were compared.Results All patients were followed-up,and the difference between the preoperative VAS score and Harris score of the two groups was not statistically significant(P＞0.05),and the VAS score and Harris score of the two groups were significantly improved at 6 months and 1 year after operation,and the BMP group was better than the allograft bone group,with significant difference(P＜0.05).At 1 year after surgery,the Harris hip score excellence rate of the BMP group was higher than that of the allograft bone group,and the difference was statistically significant(P＜0.05);the femoral head survival rate of the BMP group was higher than that of the allograft bone group,and the difference was statistically significant(P＜0.05).Conclusions Core decompression combined with BMP activity induced rod implantation was effective in the treatment of early femoral head necrosis,which accelerated the induction of new bone formation,improved the quality of new bone,provided biomechanical support for the femoral head,and effectively avoided femoral head collapse.Moreover,it has good biocompatibility and couldbe degraded and absorbed in the body,which is worthy of clinical promotion.