1.Chlorinated perfluoroalkyl ether sulfonate impairs proliferation and differentiation of neural stem cells via oxidative stress
Yaxin HAN ; Longfei FENG ; Zhijun ZHOU ; Xiuli CHANG
Journal of Environmental and Occupational Medicine 2025;42(6):684-690
Background Chlorinated perfluoroalkyl ether sulfonate Cl-PFAES, trade name F-53B, a novel per- and polyfluoroalkyl substance (PFAS), has been shown to induce multi-organ toxicity in humans and cross the blood-brain barrier. However, its toxic effects and underlying mechanisms on neural stem cells (NSCs) remain unclear. Objective To investigate the impact of F-53B on NSCs proliferation and differentiation through oxidative stress and explore its potential molecular mechanisms in associations with mitochondrial function damage and the expression of autophagy-related gene (PINK1/Parkin). Methods Primary NSCs isolated from neonatal C57BL/6 mice were used as a model and exposed to F-53B at concentrations of 0, 33, or 100 μmol·L−1 for 24 h. Cell viability was assessed using the cell counting kit-8 (CCK-8) assay, while proliferation was evaluated by the 5-ethynyl-2’-deoxyuridine (EdU) incorporation assay. Immunofluorescence staining was performed to observe differentiation phenotypes. Intracellular and mitochondrial reactive oxygen species (ROS) levels were quantified using dihydroethidium (DHE) and MitoSOX probes, respectively. Mitochondrial morphology was observed using MitoTracker Green. ATP level was measured with a commercial kit. Additionally, real-time quantitative polymerase chain reaction (qPCR) was conducted to quantify the expression of PINK1 and Parkin genes. Results Exposure to 100 μmol·L⁻¹ F-53B significantly reduced cell viability to 93.6% of the control group (P<0.01), and decreased the proportion of EdU⁺ cells (P<0.01), indicating proliferation inhibition. The differentiation analysis showed a reduction in neuronal generation, axonal shortening, and an increase in astrocytes. The 100 μmol·L−1 F-53B exposure elevated intracellular ROS to 122% (P<0.01) and mitochondrial ROS (MitoROS) to 135% (P<0.001) of the control levels, leading to mitochondrial fragmentation. The ATP levels after the F-53B exposure decreased to 62.4% relative to the control group (P<0.001). Furthermore, the mRNA expression levels of PINK1 and Par after the F-53B exposure were notably reduced (P<0.05). Conclusion F-53B may induce oxidative stress, thereby disrupting mitochondrial morphology and function while inhibiting the PINK1/Parkin-mediated mitophagy pathway, ultimately leading to impaired neural stem cell proliferation and abnormal differentiation. This study provides new insights into the neurotoxicity mechanisms of F-53B.
2.Effects of an innovative inspiratory muscle training program on postoperative pulmonary complications in patients with valvular heart disease with limited resources
Zeruxin LUO ; Yuqiang WANG ; Yaxin ZHOU
Chinese Journal of Rehabilitation Medicine 2024;39(1):39-44,69
Objective:To explore the effectiveness and feasibility of strengthening inspiratory muscle training program matching the preoperative waiting time for patients with valvular heart disease in China with limited resources in preventing postoperative pulmonary complications(PPCs). Method:Patients undergoing elective heart valve surgery were randomly divided into control group and inter-vention group,with 65 patients in each group.All the enrolled patients received a routine physical therapy pro-gram before surgery,and the intervention group received an additional 3 days of enhanced inspiratory muscle training program before surgery.The incidence of postoperative complications was recorded for all patients with-in 14 days after surgery,respiratory function and motor capacity(6-minute walking test)were tested for all patients on the day of admission and discharge,and the length of postoperative hospital stay was counted. Result:Compared with the control group,the incidence of PPCs was lower in the intervention group(OR 2.18,95%CI 1.07-4.47,P-0.03),and the walking distance was longer(P=0.01).There was no statistical difference in lung function and length of hospital stay(P>0.05),and no adverse events occurred during train-ing.There was no significant difference in general demographic characteristics between the two groups before treatment.The incidence of PPCs in the intervention group was lower than that in the control group(P<0.05),and the 6-minute walking distance at discharge was higher than that in the control group(P<0.05).There were no statistically significant differences in lung function and postoperative hospital stay between the intervention group and the control group(P>0.05),and no adverse events occurred during training. Conclusion:Enhanced inspiratory muscle training 3 days before surgery is safe and feasible in patients with elective heart valves and can reduce postoperative pulmonary complications and improve the level of motor function at discharge.
3.Application of auditory verbal learning test-Huashan version in patients with subjective cognitive decline and mild cognitive impairment
Qiumin ZHOU ; Yaxin GAO ; Tong WANG
Chinese Journal of Rehabilitation Medicine 2024;39(2):191-195,209
Objective:To explore the diagnostic value of auditory verbal learning test-Huashan version(AVLT-H)of memo-ry impairment in patients with subjective cognitive decline(SCD)and mild cognitive impairment(MCI). Method:According to the inclusion criteria,the recruited elderly were screened and divided into three groups:normal cognition(NC),SCD and MCI group.The neuropsychological tests including mini-mental state exami-nation(MMSE),Montreal cognitive assessment-Beijing version(MOCA-BJ)and AVLT-H were completed af-ter inclusion.The scores of MMSE,MoCA-B,AVLT-N2,N3,N4,N5,N6 and N7 were recorded and analyzed. Result:There were significant differences in the scores of MMSE,MoCA and AVLT-H among the three groups(P<0.0167).The adjusted Bonferroni test was used to detect significant differences in post-hoc comparison.There were significant difference in MMSE and MoCA scores between SCD and NC(P<0.001)and between MCI and NC(P<0.001).However,no significant difference between MCI and SCD was found.There were sig-nificant difference in N1 score between MCI and NC(P=0.013)and between MCI and SCD(P=0.001),but there was no significant difference between SCD and NC.There were significant difference in AVLT-N2,N3,N4,N5,N6 and N7 scores between MCI and NC(P<0.001)and between MCI and SCD(P<0.001),but there was no significant difference between SCD and NC.The area under the curve of MMSE,MoCA and AVLT-H scores were examined using NC group and SCD group as state variables,respectively.For differentiat-ing MCI and SCD,eAVLT-H scores had a larger area under the curve with higher sensitivity and specificity,N1 and N7 had the highest sensitivity.For distinguishing MCI from NC,AVLT-H and MoCA scores had a larger area under the curve with higher sensitivity and specificity,N4,N6 and N7 had the highest sensitivity. Conclusion:AVLT-H,combined with MMSE and MoCA,can improve the defining diagnostic sensitivity of MCI and SCD from normal cognition.It is recommended to routinely use AVLT-H in a routine assessment for MCI and SCD patients.
4.Value of resting state electroencephalogram in the diagnosis of Alzheimer's disease
Yaxin ZHOU ; Yuan SHAO ; Yuanlong WANG ; Ya'nan LIN ; Liangying ZHANG ; Yongjun WANG
Sichuan Mental Health 2023;36(4):313-319
BackgroundThe diagnosis of Alzheimer's disease (AD) still faces great challenges, and the advantage of electroencephalogram (EEG) diagnosis lies in its portable and non-invasive nature, so the EEG diagnosis of AD has occupied an important place in clinical research. ObjectiveTo evaluate the value of resting state EEG for AD diagnosis, and to provide references for early recognition of AD in clinical practice. MethodsClinical data of AD patients (n=59) in an Inpatient Geriatric Psychiatry Unit of Shenzhen Kangning Hospital from May 2019 to May 2022 were retrospectively analyzed, and healthy elderly individuals attending outpatient clinics at the hospital during the same period were enrolled as control group (n=54). Eight-channel resting state EEG data were acquired, and the absolute power values in the α, β, θ and δ frequency bands and the α/θ ratio were obtained and calculated using Fast Fourier Transform (FFT). Cognitive function assessments of patients were done by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Spearman correlation analysis was used to examine the correlation between EEG findings and MMSE and MoCA scores of AD patienrs. Logistic regression prediction model for AD was built using currently available EEG and clinical variables, and the model performance was assessed using the receiver operating characteristic (ROC) curve and the area under curve (AUC). ResultsThe θ-band absolute powers in the right mid-frontal (F4) and mid-lateral (F7, F8) regions were higher in AD patients than those in healthy controls, with statistically significant difference (t=-2.844, -2.825, -3.014, P<0.05 or 0.01). The absolute powers of α/θ ratio in prefrontal (Fp1, Fp2), mid-frontal (F3, F4) and mid-lateral (F7, F8) regions showed a notable reduction in AD patients compared with healthy controls, with statistical difference (t=2.081, 2.327, 3.423, 2.358, 3.272, 2.445, P<0.05 or 0.01). Spearman correlation analysis denoted that MMSE score was positively correlated with the absolute powers of α-band, β-band and α/θ ratio (r=0.206, 0.288, 0.372, P<0.05 or 0.01). MoCA score was positively correlated with β absolute powers and α/θ ratio (r=0.201, 0.315, P<0.05 or 0.01), and negatively correlated with θ absolute power (r=-0.218, P<0.05). ROC curve revealed an AUC of 0.882 (95% CI: 0.820~0.943), a sensitivity of 0.966 and a specificity of 0.673 for the AD prediction model based on EEG variables, while the prediction model for AD using comprehensive variables achieved better predictive efficacy, reaching an AUC, sensitivity and specificity of 0.946 (95% CI: 0.905~0.986), 0.948 and 0.873, respectively. ConclusionResting state EEG of AD patients is correlated with cognitive function, and are of great value in the diagnosis of AD, with θ absolute power and α/θ ratio in EEG being the most strongly correlated with AD.
5.Research progress on preoperative inspiratory muscle training for prevention of postoperative pulmonary complications in adult cardiac surgery
Zeruxin LUO ; Yuqiang WANG ; Yaxin ZHOU ; Yingqiang GUO ; Pengming YU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(10):1519-1523
In the past two decades, adult cardiac surgery has developed by leaps and bounds in both anesthetic techniques and surgical methods, whereas the incidence of postoperative pulmonary complications (PPCs) has not changed. Until now PPCs are still the most common complications after cardiac surgery, resulting in poor prognosis, significantly prolonged hospital stays and increased medical costs. With the promotion of the concept of enhanced recovery after surgery (ERAS), pre-rehabilitation has been becoming a basic therapy to prevent postoperative complications. Among them, preoperative inspiratory muscle training as a very potential intervention method has been widely and deeply studied. However, there is still no consensus about the definition and diagnostic criteria of PPCs around the world; and there is significant heterogeneity in preoperative inspiratory muscle training in the prevention of pulmonary complications after cardiac surgery in adults, which impedes its clinical application. This paper reviewed the definition, mechanism, and evaluation tools of PPCs, as well as the role, implementation plan and challenges of preoperative inspiratory muscle training in the prevention of PPCs in patients undergoing cardiac surgery, to provide reference for clinical application.
6.Effect of phenotypes of Duffy blood group on chemokine storage and chemokine scavenging function of erythrocytes
Shihang ZHOU ; Lingzi PAN ; Wenqian SONG ; Linnan SHAO ; Yaxin FAN
Chinese Journal of Blood Transfusion 2023;36(10):872-875
【Objective】 To investigate the effect of phenotypes of Duffy blood group on chemokine storage and chemokine scavenging function of erythrocytes. 【Methods】 Twenty-four erythrocyte samples were collected and tested Duffy blood phenotype using the anti-human globulin method, and erythrocyte CCL2, CCL5, CXCL8, and CCL11 content and their chemokine scavenging function using ELISA. The expression of Duffy antigens on erythrocytes was detected using a flow analyzer. 【Results】 The difference in CCL2 content(41.1±14.7 pg/mL vs 63.1±20.8 pg/mL)of erythrocyte lysate between Fy(a+b-) and Fy(a+b+) phenotype was statistically significant (P<0.05), however, the difference in the content of CCL5(794.5±320.1 pg/mL vs 846.9±359.4 pg/mL), CXCL8(59.5±34.2 pg/mL vs 49.1± 11.9 pg/mL), and CCL11(109.1±25.1 pg/mL vs 158.6 ±56.0 pg/mL) were not statistically significant (P>0.05).The difference in the scavenging function of CCL2(1471±202.1 pg/mL vs 1860±267.5 pg/mL)and CCL5 (848.5±461.7 pg/mL vs 1797±546.1pg/mL) between Fy(a+b-) and Fy(a+b+) phenotype were statistically significant (P<0.05), however, for CXCL8(1851±180.7 pg/mL vs 1 862± 248.3 pg/mL) and CCL11(691.0±125.7 pg/mL vs 781.7 ±293.8 pg/mL) scavenging function the difference were not statistically significant (P>0.05).The difference in Duffy antigen expression (mean fluorescent intensity:105.3±20.45 vs 111.9±18.30)on erythrocytes between Fy(a+b-) and Fy(a+b+) phenotype was not statistically significant (P>0.05). 【Conclusion】 The Fy(a+b+) and Fy(a+b-) phenotypes of the Duffy blood group can affect the chemokine storage and scavenging function of erythrocytes. Fy(a+b+) phenotypes are able to store more chemokines and have a stronger chemokine scavenging function than Fy(a+b-) phenotypes.
7.Performance evaluation of nucleic acid testing system for blood screening in high-altitude areas
Liang ZANG ; Lei ZHOU ; Ji DUO ; Hao LIN ; Rui BAI ; Mei YANG ; Chao DAN ; Yaxin FAN
Chinese Journal of Blood Transfusion 2023;36(10):935-939
【Objective】 To validate the performance of a nucleic acid testing(NAT) system for blood screening in the high-altitude Nagqu region of Tibet, in order to assess the capability of NAT in high-altitude areas and further enhance blood safety. 【Methods】 Various methods were employed to evaluate the analytical sensitivity, reproducibility, ability to prevent cross-contamination, and comparison between different NAT systems. 【Results】 The NAT system in the Nagqu region of Tibet achieved a 100% detection rate for high-concentration HBV DNA and HIV-1 RNA samples, and over 90% for medium-concentration samples. PROBIT analysis revealed the lower limits of detection (LOD) for HBV DNA and HIV-1 RNA to be 8.29 IU/mL (95% CI, 5.88~20.55 IU/mL) and 40.52 IU/mL (95% CI, 30.26~85.92 IU/mL), respectively. For HCV RNA genotype 2a, the LOD was 97.14 IU/mL (95% CI, 71.00~182.67 IU/mL), all of which were lower than the declared minimum detectable concentrations in the instructions. Reproducibility analysis demonstrated a 100% level of consistency within the system. Cross-contamination performance verification showed a strong ability to resist cross-contamination. Comparative analysis of repeated testing of low-concentration HBV DNA samples and multi-system testing in plain areas revealed consistency rates of 77.78%(14/18) and 77.27%(17/22), respectively, indicating certain differences between the NAT system in Nagqu region and other systems. 【Conclusion】 The NAT system exhibited excellent performance in blood screening at high altitudes. The results of performance validation in high-altitude blood screening NAT systems were largely consistent with those in plain areas, providing a reliable basis for enhancing blood safety in high-altitude regions.
8.Analysis of ABO gene mRNA expression in peripheral blood of patients with acute myeloid leukemia
Shihang ZHOU ; Ni WANG ; Ming LIU ; Yaxin FAN
Chinese Journal of Blood Transfusion 2023;36(2):112-115
【Objective】 To investigate the expression characteristics of ABO gene mRNA in peripheral blood of patients with acute myeloid leukemia. 【Methods】 The RNA-seq data of acute myeloid leukemia in TCGA database and the whole blood RNA-seq data in GTEx database were downloaded. The difference of ABO gene mRNA expression between acute myeloid leukemia and GTEx whole blood samples was analyzed by R software, and the relationship between ABO gene mRNA expression and DNA methylation, immune infiltration and prognosis was analyzed. 【Results】 The expression level of ABO gene mRNA in acute myeloid leukemia(median: 1.333, P
9.Development and application of drug-induced liver injury surveillance and assessment system
Chao AI ; Zhaoshuai JI ; Yaxin ZHANG ; An LIU ; Xuesi ZHOU ; Zhonghao CHEN ; Ji WU
China Pharmacy 2023;34(19):2409-2413
OBJECTIVE To establish the drug-induced liver injury (DILI) surveillance and assessment system (DILI-SAS), and to improve the diagnostic efficiency of clinical DILI. METHODS The DILI-SAS was constructed by using natural language processing technology to mine and utilize all inpatient medical record data, and combined with Roussel Uclaf causality assessment method (RUCAM). The medical records of 19 445 hospitalized patients from August 2022 to January 2023 were detected to verify the performance of the system and manually analyze the basic data of patients with DILI and the distribution of the first suspected drugs. RESULTS The overall accuracy rate of the DILI-SAS system was 91.95%, and the recall rate was 93.20%. Seventy-five DILI cases were detected, and the DILI incidence rate was 385.70/100 000 people. The efficiency of DILI monitoring by human- computer coupling was increased by about 60 times of manual monitoring; males (61.33%) and patients over 60 years old (56.00%) were the most common in the 75 cases of DILI. The clinical type of liver injury was hepatocyte injury (69.33%), the incubation period was mainly 5-90 days after treatment (62.67%), and the RUCAM score between 3 and 5 was the most common (66.67%); pharmacological distribution of the first suspected drugs was mainly dihydropyridines, HMG CoA reductase inhibitors, proton pump inhibitors, etc. The specific drugs were atorvastatin, omeprazole, ceftriaxone, metronidazole and other drugs. CONCLUSIONS The establishment of DILI-SAS can improve the evaluation efficiency on the basis of ensuring the accuracy degree, and provide a solution for the early identification, diagnosis and evaluation of clinical DILI.
10.Expression of CDKN1B in colorectal cancer and its relationship with clinicopathological features
Yan WU ; Yaxin LIU ; Yijun MA ; Wei HAN ; Caiting ZHOU ; Xuebing YAN ; Jian XU ; Lei WANG
Cancer Research and Clinic 2023;35(12):899-903
Objective:To explore the relationship between CDKN1B expression and clinicopathological features in colorectal cancer.Methods:Human Protein Atlas (HPA) database and Gene Expression Profiling Interactive Analysis (GEPIA) database were used to analyze the expression of CDKN1B in colorectal cancer tissues and its relationship with the prognosis of colorectal cancer. The data of 98 patients with colorectal cancer who underwent surgery from January 2020 to December 2021 at Yixing Clinical College of Yangzhou University Medical School were retrospectively analyzed, and pathological specimens were collected. Immunohistochemistry method was used to detect CDKN1B protein expression level in colorectal cancer and paracancerous normal tissues (2 cm from the tumor site) and the correlation of CDNK1B expression with clinicopathological characteristics was analyzed.Results:The results of bioinfomatics analysis and the prediction from HPA database and GEPIA database suggested that the expression level of CDKN1B in colorectal cancer was lower than that in the normal colorectal tissues; In HPA database, the 5-year overall survival rate of patients in the CDKN1B high expression (425 cases) was higher than that of those in the CDKN1B low expression (172 cases) (65% vs.51%), and the difference in the overall survival of both group was statistically significant ( P < 0.001). GEPIA database staging module analysis showed that CDKN1B gene expression level was correlated with the pathological stage of patients with colorectal cancer ( P = 0.033). Immunohistochemistry analysis showed that CDKN1B expression was localized in the nucleus and cytoplasm. The proportion of patients with CDKN1B high expression in colorectal cancer tissues was lower than that in paracancerous normal tissues [18.37% (18/98) vs. 90.82% (89/98), P < 0.01]. The proportion of CDKN1B high expression in cancer tissues of colorectal cancer patients with poor differentiation [poor differentiation vs. high-middle differentiation: 3.70% (1/27) vs. 23.94% (17/71)], lymph node metastasis [metastasis vs. non-metastasis: 6.38% (3/53) vs. 29.41% (15/45)], TNM higher stage [stage Ⅳ vs. Ⅲ vs. Ⅱ vs. Ⅰ: 5.00% (1/20) vs. 13.95% (3/33) vs. 20.59% (8/30) vs. 36.36% (6/15)] was lower (all P < 0.05), while there were no statistically significant differences in the proportion of patients with CDKMB high expression in colorectal cancer tissues among different subgroups stratified by gender, age and tumor size (all P > 0.05). Conclusions:CDKN1B is mainly expressed in the nucleus and cytoplasm, and is lowly expressed in colorectal cancer. The lower CDKN1B expression may indicate the poorer prognosis of patients. CDKN1B can be used as a marker for clinical diagnosis, treatment and prognosis evaluation of colorectal cancer.

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