1.Hepatorenal toxicity of combined yttrium and lead oral exposure in male Sprague-Dawley rats
Yu YE ; Yuexuan WANG ; Xiaohao TANG ; Minqi ZHU ; Yunzhi LIU ; Baojun ZHANG ; Yanmin WANG ; Changmao LONG
China Occupational Medicine 2026;53(2):130-136
Objective To investigate the toxic effects of combined yttrium and lead exposure on liver and kidney functions in male Sprague-Dawley (SD) rats. Methods Adult male specific pathogen-free SD rats were randomly divided into four groups. Rats in the low-, medium-, and high-dose groups were co-administered with yttrium acetate (10.0, 50.0, and 100.0 mg/kg body weight, respectively) and lead acetate (4.0, 20.0, and 40.0 mg/kg body weight, respectively) by intragastric gavage, once per day for 28 consecutive days. Rats in the control group received an equal volume of deionized water. Yttrium and lead levels in whole blood, liver, and kidney tissues of the rats were measured using inductively coupled plasma mass spectrometry. Serum index of liver and kidney function were measured by a double reagent method, and histopathological changes in the liver and kidney were observed. Results The body weights of rats in all the three exposure groups were lower than those in the control group from day 14 of exposure until the end of exposure (all P<0.05). Body weight gain of rats was observed only in the low-dose group at day 28, whereas no body weight gain was observed throughout the exposure period in the medium- and high-dose groups. Histopathological examination showed dose-dependent liver and kidney injuries in rats of the three exposure groups compared with the control group. Specifically, the liver exhibited widening of intercellular spaces and increased inflammatory cell infiltration, while the kidney showed increased tissue hemorrhage and increased damage to glomeruli and renal tubules. Lead levels in whole blood, liver, and kidney tissues of the rats were higher than yttrium levels in all the three exposure groups (all P<0.05). Blood yttrium levels in rats of the high-dose group were higher than those in the other three groups (all P<0.05), and yttrium levels in the liver and kidney tissues of the three exposure groups were higher than those in the control group (all P<0.05). Lead levels in whole blood, liver, and kidney tissues of the rats increased with increasing exposure dose (all P<0.05). At the end of exposure, the kidney organ coefficient of rats in the high-dose group was higher than those in the other three groups (all P<0.05). The serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ratio of rats in the high‑dose group was lower than that in the control group (P<0.05). The serum urea and uric acid levels in the medium‑ and high‑dose groups were lower than those in the control group (both P<0.05). The serum cystatin C level in the high‑dose group was higher than that in the control group (P<0.05). Blood yttrium and blood lead levels were each negatively correlated with serum ALT/AST ratio, serum urea nitrogen, and uric acid levels (both P<0.05). Both yttrium and lead levels in liver tissue were each negatively correlated with serum ALT/AST ratio (all P<0.05). Both yttrium and lead levels in kidney tissue were each negatively correlated with both serum urea nitrogen and uric acid levels (all P<0.05), and each positively correlated with serum cystatin C levels (both P<0.05). Conclusion Co-exposure to yttrium and lead induces dose‑dependent hepatotoxicity and nephrotoxicity in male SD rats. Lead exhibits a more pronounced accumulation effect and contributes more substantially to the observed toxicity.
2.Feasibility of applying auxiliary analysis software to chromosomal aberration analysis of radiation workers
Ping WANG ; Lin HAN ; Jie LI ; Shasha DU ; Yunfei ZHANG ; Xiaohao LI ; Siqi FANG ; Yu GAO ; Xianfei NIU ; Yumin LYU
Chinese Journal of Radiological Medicine and Protection 2025;45(8):750-756
Objective:To explore the feasibility of the new auxiliary analysis software in chromosomal aberration analysis of radiation workers during occupational health examinations.Methods:Health examination data of 2 469 radiation workers in Henan province were collected. Manual analysis of chromosomal aberrations in peripheral blood lymphocytes was conducted using the new auxiliary software and the Ikaros software. Then, the chromosomal aberrations detected using both software tools were compared.Results:The new auxiliary software yielded a lower chromosomal aberration rate among radiation workers compared with the Ikaros software [(0.314 ± 0.014)% vs. (0.391 ± 0.022)%, χ2 = 9.24, P = 0.002]. Notably, the new auxiliary software yielded a significantly lower rate of acentric fragments (ace) [(0.136 ± 0.009)% vs. (0.209 ± 0.020)%, χ2= 17.76, P < 0.001]. However, no statistically significant differences were observed between the result of the two software tools in the rates of dicentrics plus rings (dic + r) and translocations ( P > 0.05). According to the GBZ/T 248-2014 standard, the differences in abnormality rates of chromosomal aberrations between the two groups had no statistically significance ( P > 0.05), with both groups showing an abnormality rate of 0 for ace. Furthermore, the new auxiliary software could double the detection efficiency. Among pre-service radiation workers of various occupations, the differences in the chromosomal aberrations detected using the two software tools exhibited statistical significance ( χ2 = 10.26, P = 0.001). In contrast, the differences in the chromosomal aberrations among in-service and post-service radiation workers had no statistically different significance ( P>0.05). The Poisson regression analysis result demonstrated that the rate of chromosomal aberrations excluding ace was affected by age ( z = 2.73, P = 0.006), while gender, analysis method, service status, and occupation had no impact. Conclusions:The two software tools yielded largely consistent result in detecting chromosomal aberrations induced by exposure to ionizing radiation. Notably, the new auxiliary software can significantly improve detection efficiency, indicating the feasibility of applying it to chromosomal aberration analysis among radiation workers.
3.Screening of Differentially Expressed Key Genes in Head and Neck Squamous Cell Carcinoma and Analysis of Their Prognostic Value Based on GEO and TCGA Databases
Sihao LIU ; Xiaohao ZHANG ; Zhipeng XU
Journal of Modern Laboratory Medicine 2025;40(2):47-52,58
Objective To screen key differentially expressed genes in head and neck squamous cell carcinoma(HNSCC)and analyze their prognostic value,based on biological information from gene expression omnibus(GEO)and the cancer genome atlas(TCGA)databases.Methods HNSCC mRNA expression data(GSE74530)were downloaded from the GEO database as a test dataset,and differentially expressed genes(DEGs)were identified.The biological function of DEGs in HNSCC was investigated by gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.HNSCC mRNA expression data were obtained from the TCGA database as a validation dataset to preliminarily verify the expression of DEGs in HNSCC tissues and normal tissues.Seven up-regulated DEGs variants were analyzed using the cBioPortal database,and their effects on the survival of HNSCC patients were evaluated by the Kaplan-meier method and COX regression analysis.The co-expressed genes of ATP6V1C1 were analyzed by the cBioPortal database.Results A total of 1 432 differential genes were screened from HNSCC tissue and paracancerous tissue in the GSE74530 test dataset,among which 7 of the 10 most significant genes were up-regulated,respectively:MMP1,WDR66,PTPRZ1,TEAD4,RBM38,ATP6V1C1 and CBLB were downregulated by CGNL1,LOC100506990 and ADH1B.GO and KEGG enrichment analysis showed that HNSCC tissue differential genes were mainly enriched in lymphocyte migration and extracellular matrix regulation pathways.The TCGA dataset confirmed that 7 upregulated DEGs were highly expressed in HNSCC.cBioPortal analysis showed that the proportion of ATP6V1C1 gene changes was the highest among the 7 up-regulated genes,and the overall survival rate of patients with high expression of ATP6V1C1 gene decreased significantly.Correlation analysis showed that BIRC5 was the most closely related gene to ATP6V1C1.Conclusion MMP1,WDR66,PTPRZ1,TEAD4,RBM38,ATP6V1C1 and CBLB were highly expressed in HNSCC patients,among which ATP6V1C1 was the most significant,and its expression level was associated with poor prognosis in HNSCC patients.ATP6V1C1 is expected to be a biomarker for early diagnosis and prognosis of HNSCC,providing a new idea for clinical diagnosis and treatment.
4.Prognostic study of neoadjuvant therapy for pancreatic cancer based on propensity score matching and subgroup analysis
Xiaohao ZHENG ; Jingyu ZHANG ; Xiaojie CHEN ; Zhen HAO ; Jing LIU ; Zewen ZHANG ; Wanqing YU ; Yun YANG
International Journal of Surgery 2025;52(4):230-238
Objective:To investigate whether neoadjuvant therapy can improve the prognosis of patients with pancreatic cancer.Methods:A retrospective case-control study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database on 12, 103 patients who underwent surgical treatment between January 1, 2010, and December 31, 2021. Patients were divided into the neoadjuvant therapy group ( n=3 276) and the upfront surgery group ( n=8 827) based on whether they received neoadjuvant treatment. The neoadjuvant therapy group included 2 342 patients receiving neoadjuvant chemotherapy and 934 patients receiving neoadjuvant chemoradiotherapy. The upfront surgery group consisted of 4 335 patients receiving adjuvant chemotherapy, 1 987 patients receiving adjuvant chemoradiotherapy, 63 patients receiving adjuvant radiotherapy, and 2 442 patients undergoing surgery alone. Propensity score matching was used to eliminate group differences and create a cohort with no statistical differences in other clinicopathological features except for the grouping variable. Variables such as age, gender, tumor location, race, population of residence, tumor diameter, household income, TNM stage, and information on radiotherapy and chemotherapy were used for 1∶1 case matching. T stage, N stage, and the use of radiotherapy or chemotherapy were matched exactly. After matching, 1 182 patients were included in each group: the neoadjuvant therapy group contained 1 155 patients receiving neoadjuvant chemoradiotherapy and 27 receiving neoadjuvant chemotherapy, while the upfront surgery group comprised 848 patients receiving adjuvant chemotherapy and 334 receiving adjuvant chemoradiotherapy. TNM staging was reported according to the 7th edition of the AJCC guidelines. The primary outcome was overall survival. Measurement data with skewed distributions were expressed as M( Q1, Q3), and intergroup comparisons were conducted using the Wilcoxon rank-sum test. Categorical data were compared using the chi-square test or the Fisher′s exact test. The Log-rank test and subgroup analyses to assess interactions between neoadjuvant therapy and subgroup in COX regression models were used to compare survival benefits across variables. Landmark analysis was performed to create segmented survival curves, studying the impact of neoadjuvant therapy on prognosis during different follow-up periods. Results:The neoadjuvant therapy group had a higher proportion of T 4 tumor involving celiac axis, superior mesenteric artery, and/or common hepatic artery compared to the upfront surgery group (14.7% vs 2.8%, P<0.001). Additionally, significant differences were observed between groups in terms of race, location, population of residence, age, tumor diameter, tumor stage, and adjuvant therapy regimen ( P<0.05). The median overall survival time in the neoadjuvant therapy group was 30 months, compared to 22 months in the upfront surgery group ( P<0.001). In the neoadjuvant therapy group, the median survival was 30 months for both neoadjuvant chemotherapy and chemoradiotherapy patients; in the upfront surgery group, it was 26 months for both adjuvant chemotherapy and chemoradiotherapy patients, 17 months for adjuvant radiotherapy patients, and 12 months for surgery-only patients. After propensity score matching, there were no differences in the distribution of clinical characteristics between groups ( P>0.05), and all patients in the matched cohort had received chemotherapy. The matched neoadjuvant therapy group had a longer median overall survival compared to the upfront surgery group (30 months vs 27 months, P<0.001). Subgroup interaction analysis revealed that T stage had a significant interaction with neoadjuvant therapy, both before (T 4 stage: HR=0.382, 95% CI: 0.319-0.458; T 2-T 3 stages: HR=0.696, 95% CI: 0.656-0.738; T 1 stage: HR=1.199, 95% CI: 0.867-1.657; interaction P<0.001) and after matching (T 4 stage: HR=0.581, 95% CI: 0.414-0.814; T 2-T 3 stages: HR=0.827, 95% CI: 0.734-0.931; T 1 stage: HR=1.320, 95% CI: 0.716-2.433; interaction P=0.043). Subgroup interaction analysis indicated that T 1 patients did not benefit from neoadjuvant therapy; survival curves plotted for matched T 1 patients showed no difference in survival between the neoadjuvant therapy group and the upfront surgery group ( P=0.323). Conversely, non-T 1 (T 2-T 4) stage patients showed significant survival benefits in both unmatched and matched cohorts ( P<0.001). Landmark analysis showing that the survival benefits occurred mainly in the early postoperative period of up to 3 years ( P<0.001), but there was no difference in overall survival between the neoadjuvant therapy group and the upfront surgery group of >3 years ( P>0.05). Patients with Arterial invasion (T 4 stage compared to T 1-T 3 stages) showed a similarly significant interaction with the benefit of neoadjuvant therapy in both the pre-matching cohort (interaction P<0.001) and the post-matching cohort (interaction P=0.037). Patients with T 4 stage disease in the neoadjuvant therapy group had longer overall survival compared to the upfront surgery group (median overall survival in pre-matching cohort: 30 months vs 13 months, P<0.001; median overall survival in post-matching cohort: 28 months vs 18 months, P=0.001). Among T 4 stage patients in the post-matching cohort, neoadjuvant therapy provided significant survival benefits during the early postoperative period of up to 3 years ( P=0.001). However, there was no difference in overall survival between the neoadjuvant therapy group and the direct surgery group beyond 3 years( P=0.729). Conclusions:The prognosis in the neoadjuvant therapy group was better than in the upfront surgery group. Propensity score matching and subgroup interaction analysis showed that non-T 1 and T 4 stage patients benefited more from neoadjuvant therapy, with benefits mainly seen in the early postoperative period (≤3 years).
5.Feasibility of applying auxiliary analysis software to chromosomal aberration analysis of radiation workers
Ping WANG ; Lin HAN ; Jie LI ; Shasha DU ; Yunfei ZHANG ; Xiaohao LI ; Siqi FANG ; Yu GAO ; Xianfei NIU ; Yumin LYU
Chinese Journal of Radiological Medicine and Protection 2025;45(8):750-756
Objective:To explore the feasibility of the new auxiliary analysis software in chromosomal aberration analysis of radiation workers during occupational health examinations.Methods:Health examination data of 2 469 radiation workers in Henan province were collected. Manual analysis of chromosomal aberrations in peripheral blood lymphocytes was conducted using the new auxiliary software and the Ikaros software. Then, the chromosomal aberrations detected using both software tools were compared.Results:The new auxiliary software yielded a lower chromosomal aberration rate among radiation workers compared with the Ikaros software [(0.314 ± 0.014)% vs. (0.391 ± 0.022)%, χ2 = 9.24, P = 0.002]. Notably, the new auxiliary software yielded a significantly lower rate of acentric fragments (ace) [(0.136 ± 0.009)% vs. (0.209 ± 0.020)%, χ2= 17.76, P < 0.001]. However, no statistically significant differences were observed between the result of the two software tools in the rates of dicentrics plus rings (dic + r) and translocations ( P > 0.05). According to the GBZ/T 248-2014 standard, the differences in abnormality rates of chromosomal aberrations between the two groups had no statistically significance ( P > 0.05), with both groups showing an abnormality rate of 0 for ace. Furthermore, the new auxiliary software could double the detection efficiency. Among pre-service radiation workers of various occupations, the differences in the chromosomal aberrations detected using the two software tools exhibited statistical significance ( χ2 = 10.26, P = 0.001). In contrast, the differences in the chromosomal aberrations among in-service and post-service radiation workers had no statistically different significance ( P>0.05). The Poisson regression analysis result demonstrated that the rate of chromosomal aberrations excluding ace was affected by age ( z = 2.73, P = 0.006), while gender, analysis method, service status, and occupation had no impact. Conclusions:The two software tools yielded largely consistent result in detecting chromosomal aberrations induced by exposure to ionizing radiation. Notably, the new auxiliary software can significantly improve detection efficiency, indicating the feasibility of applying it to chromosomal aberration analysis among radiation workers.
6.Assessment and management of malnutrition in patients with cirrhosis combined with hepatic encephalopathy
Yang XU ; Juan KANG ; Xiaohao WANG ; Lu ZHANG ; Dachuan CAI
Chinese Journal of Hepatology 2025;33(4):402-408
Hepatic encephalopathy and malnutrition due to hyperammonemia often interact with each other, forming a vicious circle in patients with cirrhosis. In addition, hepatic encephalopathy and malnutrition have a high incidence in patients with cirrhosis, which seriously affects the quality of life and prognosis. Therefore, identifying whether malnutrition is present in patients with cirrhosis combined with hepatic encephalopathy is crucial for providing appropriate interventions.This article reviews the pathogenesis, nutritional assessment methods, and nutritional management of malnutrition in patients with liver cirrhosis combined with hepatic encephalopathy.
7.Screening of Differentially Expressed Key Genes in Head and Neck Squamous Cell Carcinoma and Analysis of Their Prognostic Value Based on GEO and TCGA Databases
Sihao LIU ; Xiaohao ZHANG ; Zhipeng XU
Journal of Modern Laboratory Medicine 2025;40(2):47-52,58
Objective To screen key differentially expressed genes in head and neck squamous cell carcinoma(HNSCC)and analyze their prognostic value,based on biological information from gene expression omnibus(GEO)and the cancer genome atlas(TCGA)databases.Methods HNSCC mRNA expression data(GSE74530)were downloaded from the GEO database as a test dataset,and differentially expressed genes(DEGs)were identified.The biological function of DEGs in HNSCC was investigated by gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.HNSCC mRNA expression data were obtained from the TCGA database as a validation dataset to preliminarily verify the expression of DEGs in HNSCC tissues and normal tissues.Seven up-regulated DEGs variants were analyzed using the cBioPortal database,and their effects on the survival of HNSCC patients were evaluated by the Kaplan-meier method and COX regression analysis.The co-expressed genes of ATP6V1C1 were analyzed by the cBioPortal database.Results A total of 1 432 differential genes were screened from HNSCC tissue and paracancerous tissue in the GSE74530 test dataset,among which 7 of the 10 most significant genes were up-regulated,respectively:MMP1,WDR66,PTPRZ1,TEAD4,RBM38,ATP6V1C1 and CBLB were downregulated by CGNL1,LOC100506990 and ADH1B.GO and KEGG enrichment analysis showed that HNSCC tissue differential genes were mainly enriched in lymphocyte migration and extracellular matrix regulation pathways.The TCGA dataset confirmed that 7 upregulated DEGs were highly expressed in HNSCC.cBioPortal analysis showed that the proportion of ATP6V1C1 gene changes was the highest among the 7 up-regulated genes,and the overall survival rate of patients with high expression of ATP6V1C1 gene decreased significantly.Correlation analysis showed that BIRC5 was the most closely related gene to ATP6V1C1.Conclusion MMP1,WDR66,PTPRZ1,TEAD4,RBM38,ATP6V1C1 and CBLB were highly expressed in HNSCC patients,among which ATP6V1C1 was the most significant,and its expression level was associated with poor prognosis in HNSCC patients.ATP6V1C1 is expected to be a biomarker for early diagnosis and prognosis of HNSCC,providing a new idea for clinical diagnosis and treatment.
8.Assessment and management of malnutrition in patients with cirrhosis combined with hepatic encephalopathy
Yang XU ; Juan KANG ; Xiaohao WANG ; Lu ZHANG ; Dachuan CAI
Chinese Journal of Hepatology 2025;33(4):402-408
Hepatic encephalopathy and malnutrition due to hyperammonemia often interact with each other, forming a vicious circle in patients with cirrhosis. In addition, hepatic encephalopathy and malnutrition have a high incidence in patients with cirrhosis, which seriously affects the quality of life and prognosis. Therefore, identifying whether malnutrition is present in patients with cirrhosis combined with hepatic encephalopathy is crucial for providing appropriate interventions.This article reviews the pathogenesis, nutritional assessment methods, and nutritional management of malnutrition in patients with liver cirrhosis combined with hepatic encephalopathy.
9.Accuracy of portable hemoglobinometer in maintenance hemodialysis patients
Xiaohao ZHANG ; Fanglin TANG ; Jialing RAO ; Yuanqing LI ; Wei LI ; Cailian CHENG ; Hui PENG
Chinese Journal of Nephrology 2024;40(1):49-52
This study aims to evaluate the accuracy of portable hemoglobinometer (Hemocue Hb 201+ hemoglobin analyzer) in patients with maintenance hemodialysis (MHD) and its diagnostic value for anemia. The data of venous hemoglobulin (Hb) and fingertip capillary hemoglobulin (DHb) in MHD patients from Lingnan Hospital, the Third Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed, and the correlation and difference between DHb and Hb and the accuracy of DHb in the diagnosis of anemia were evaluated. A total of 105 patients were included in the study. There was no significant difference between the paired DHb and Hb [(109±21) g/L vs. (108±20) g/L, t=-1.284, P=0.202]. Pearson correlation analysis showed that DHb was positively correlated with Hb ( r=0.929, P<0.001). Linear regression analysis showed that DHb and Hb met the regression equation Hb=0.88×DHb+12.23, and P<0.001. Bland-Altman analysis showed that the differences between the paired DHb and Hb was (1.0±7.8) g/L with the limit of agreement as (-14.2, 16.2) g/L. The mean percentage of the differences in Hb was 1% with limit of agreement as (-13.7%, 15.7%). A DHb of >110 g/L was 0.90 sensitive and 0.83 specific to identify patients with an Hb >110 g/L and its positive and negative predictive values were 0.84 and 0.90, respectively. It suggests that, in MHD patients, Hemocue Hb 201+ analyzer shows good accuracy, and can be used to monitor the Hb trend and serve as a screen method for those reaching target Hb.
10.Correlation between serum proprotein convertase subtilisin/kexin type 9 and white matter hyperintensities of presumed vascular origin in healthy individuals
Xiuli SHU ; Yun LI ; Zhenqian HUANG ; Ying ZHAO ; Xiaohao ZHANG ; Wusheng ZHU ; Yi XIE ; Xinfeng LIU
International Journal of Cerebrovascular Diseases 2024;32(10):754-759
Objective:To investigate the correlation between serum proprotein convertase subtilisin/Kexin type 9 (PCSK9) level and white matter hyperintensities (WMHs) in healthy population.Methods:Consecutive healthy individuals underwent routine physical examinations at the Department of Neurology, Jinling Hospital Affiliated to Medical School of Nanjing University (April 2023 to December 2023) and Hexi Branch of Nanjing First Hospital (March 2024 to April 2024) were included prospectively. Enzyme-linked immunosorbent assay was used to detect serum PCSK9 level. The Fazekas scale was used to assess the severity of WMHs (total score 0-6) and they were divided into no or mild WMHs group (0-2) and moderate to severe WMHs group (3-6). Multivariate logistic regression analysis was used to determine the independent correlation between the serum PCSK9 level and the severity of WMHs. Results:A total of 177 subjects were enrolled, including 110 males (62.1%), aged 66.7±10.1 years. The median serum PCSK9 level was 203.9 ng/L. According to the Fazekas score, there were 102 patients (51.6%) in the no or mild WMHs group, and 75 (42.4%) in the moderate to severe WMHs group. One way analysis of variance showed that serum PCSK9 level significantly increased with the increase of WMHs total score ( P=0.001). The serum PCSK9 level in the moderate to severe WMHs group was significantly higher than that in the no or mild WMHs group (437.2±260.4 ng/L vs. 217.9±141.7 ng/L; P=0.001). Multivariate logistic regression analysis showed that after adjusting for age, gender, and other confounding factors, there was a significant independent correlation between higher serum PCSK9 level and moderate to severe WMHs (odds ratio 3.201, 95% confidence interval 2.107-5.082; P=0.001). Conclusion:Higher serum PCSK9 level is an independent risk factor for moderate to severe WMHs in healthy individuals.

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