1.Expert consensus on neoadjuvant PD-1 inhibitors for locally advanced oral squamous cell carcinoma (2026)
LI Jinsong ; LIAO Guiqing ; LI Longjiang ; ZHANG Chenping ; SHANG Chenping ; ZHANG Jie ; ZHONG Laiping ; LIU Bing ; CHEN Gang ; WEI Jianhua ; JI Tong ; LI Chunjie ; LIN Lisong ; REN Guoxin ; LI Yi ; SHANG Wei ; HAN Bing ; JIANG Canhua ; ZHANG Sheng ; SONG Ming ; LIU Xuekui ; WANG Anxun ; LIU Shuguang ; CHEN Zhanhong ; WANG Youyuan ; LIN Zhaoyu ; LI Haigang ; DUAN Xiaohui ; YE Ling ; ZHENG Jun ; WANG Jun ; LV Xiaozhi ; ZHU Lijun ; CAO Haotian
Journal of Prevention and Treatment for Stomatological Diseases 2026;34(2):105-118
Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.
2.Incidence and determinants of posttraumatic stress disorder at three months following a road traffic accident
Luodong YANG ; Haohao LI ; Yao MENG ; Liang JIANG ; Min HU ; Guiqing ZHANG
Acta Universitatis Medicinalis Anhui 2026;61(2):314-320
ObjectiveTo investigate the incidence and influencing factors of posttraumatic stress disorder (PTSD) three months after a traffic accident, and to explore the role of social support and coping strategies. MethodsA total of 117 individuals exposed to trauma following road traffic accidents were recruited. General demographic and clinical information was collected within one week, and the hamilton anxiety rating scale (HAMA), the hamilton depression rating scale-24 (HAMD-24), the social support rating scale (SSRS), and the simplified coping style questionnaire (SCSQ) were administered. A 3-month follow-up was subsequently conducted, during which PTSD symptoms were assessed using the post-traumatic stress disorder checklist for DSM-5 (PCL-5). Participants were divided into a PTSD group and a non-PTSD group according to whether PTSD occurred. Between-group comparisons were performed using the Mann-Whitney U non-parametric test or the χ2 test, as appropriate. Spearman correlation analysis was used to examine the associations between general characteristics and PCL-5 scores. Binary Logistic regression was applied to identify factors influencing PTSD, and receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic value of the SCSQ and SSRS. ResultsDuring the 3-month follow-up of the 117 trauma-exposed individuals, 17 cases developed PTSD, with a higher proportion of females (70.59%). Between-group comparisons showed that, compared with the PTSD group, the non-PTSD group had higher scores for positive coping, objective support, and subjective support (P<0.05), and lower scores for negative coping, HAMA, HAMD, and PCL-5 (P<0.05). Correlation analysis indicated that female gender, negative coping, and higher HAMA and HAMD scores were associated with greater PTSD severity. Logistic regression analysis demonstrated that educational level (OR=1.715, 95% CI: 1.020-2.883, P=0.042) and negative coping (OR=1.590, 95% CI: 1.003-2.522, P=0.048) were risk factors for PTSD, whereas objective support (OR=0.646, 95% CI: 0.451-0.925, P=0.017) was a protective factor. The ROC analysis showed that the total SCSQ score and its negative and positive coping dimensions, the total SSRS score and its subjective and objective support dimensions, as well as their combined use, all demonstrated good discriminative ability in distinguishing between the PTSD and non-PTSD groups. ConclusionThe results suggest that individuals who are female, with higher HAMA and HAMD scores after a motor vehicle accident, and those with lower social support and negative coping strategies, should be given particular attention. Early interventions for these individuals may reduce the incidence of PTSD.
3.Research on intelligent fetal heart monitoring model based on deep active learning.
Bin QUAN ; Yajing HUANG ; Yanfang LI ; Qinqun CHEN ; Honglai ZHANG ; Li LI ; Guiqing LIU ; Hang WEI
Journal of Biomedical Engineering 2025;42(1):57-64
Cardiotocography (CTG) is a non-invasive and important tool for diagnosing fetal distress during pregnancy. To meet the needs of intelligent fetal heart monitoring based on deep learning, this paper proposes a TWD-MOAL deep active learning algorithm based on the three-way decision (TWD) theory and multi-objective optimization Active Learning (MOAL). During the training process of a convolutional neural network (CNN) classification model, the algorithm incorporates the TWD theory to select high-confidence samples as pseudo-labeled samples in a fine-grained batch processing mode, meanwhile low-confidence samples annotated by obstetrics experts were also considered. The TWD-MOAL algorithm proposed in this paper was validated on a dataset of 16 355 prenatal CTG records collected by our group. Experimental results showed that the algorithm proposed in this paper achieved an accuracy of 80.63% using only 40% of the labeled samples, and in terms of various indicators, it performed better than the existing active learning algorithms under other frameworks. The study has shown that the intelligent fetal heart monitoring model based on TWD-MOAL proposed in this paper is reasonable and feasible. The algorithm significantly reduces the time and cost of labeling by obstetric experts and effectively solves the problem of data imbalance in CTG signal data in clinic, which is of great significance for assisting obstetrician in interpretations CTG signals and realizing intelligence fetal monitoring.
Humans
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Pregnancy
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Female
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Cardiotocography/methods*
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Deep Learning
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Neural Networks, Computer
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Algorithms
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Fetal Monitoring/methods*
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Heart Rate, Fetal
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Fetal Distress/diagnosis*
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Fetal Heart/physiology*
4.Relationship between myelin changes in cerebellar gray matter and cognitive function in PTSD
Bin LI ; Min HU ; Luodong YANG ; Ziwei ZHANG ; Yuanyuan HU ; Guiqing ZHANG
The Journal of Practical Medicine 2025;41(14):2183-2190
Objective To explore the differences in cerebellar gray matter myelin content and gray matter volume between patients with post-traumatic stress disorder(PTSD)and healthy controls(HC)using the ratio of T1-weighted(T1w)and T2-weighted(T2w)images and voxel-based morphometry(VBM)analysis,and to examine the correlation of these differences with cognitive function.Methods A total of 30 PTSD patients and 30 healthy controls(HC)matched for age,gender,and education level were included in this study.Cognitive function was assessed using the Montreal Cognitive Assessment(MoCA),and magnetic resonance imaging(MRI)scans were performed for both groups.Two-sample t-tests were used to analyze the group differences in cerebellar gray matter region T1w/T2w ratios and gray matter volume.Spearman partial correlation analysis was used to explore the correla-tion between the intergroup differences and cognitive function.Results Compared to the HC group,the PTSD group showed a reduced left cerebellar gray matter T1w/T2w ratio(voxel level P<0.001,cluster level P<0.05,GRF corrected).The areas with decreased T1w/T2w ratio in the PTSD group also exhibited reduced gray matter volume(voxel P<0.005,cluster P<0.05,GRF corrected).Correlation analysis revealed a positive correlation between the left cerebellar gray matter T1w/T2w ratio and the severity of cognitive impairment in the PTSD group.Conclusions The PTSD group exhibited reduced myelin content and gray matter volume in the left cerebellar gray matter region,with both myelin reduction and volume loss positively correlating with the severity of cognitive impairment.The T1w/T2w ratio provides a new perspective for studying myelination in PTSD patients.
5.Best evidence summary of nutritional management in patients with acute-on-chronic liver failure
Jiayi TANG ; Guiqing TANG ; Na ZHANG ; Xiaobo LI
Chinese Journal of Nursing 2025;60(5):581-589
Objective To retrieve,evaluate and synthesize the best evidence for nutritional management in patients with acute-on-chronic liver failure.Methods Evidence on nutritional management of patients with acute-on-chronic liver failure was systemically retrieved from the clinical decision support systems,guideline websites,professional association websites and databases,such as Cochrane Library,Joanna Briggs Institute,PubMed,Embase,CINAHL,Web of Science,VIP database,CNKI and CBM,including clinical decisions,guidelines,expert consensuses,evidence summaries and systematic reviews from inception to July 16,2024.Researchers trained in evidence-based nursing used authoritative tools to evaluate the methodological quality of the literature,and extracted and synthesized evidence according to the theme.Results A total of 13 articles were included,including 1 clinical decision,8 guidelines,and 4 expert consensuses.The best evidence included 26 pieces of evidence in 6 areas,namely the nutrition support team,nutritional assessment,energy and protein intake,oral nutrition support,enteral and parenteral nutrition support,and management of complications.Conclusion This study summarizes the best evidence for nutritional management in patients with acute-on-chronic liver failure,which can provide a basis for their standardized management.Medical staff should evaluate the availability of evidence from multiple perspectives when applying it.
6.Changes in myelin basic protein expression in the hippocampus and prefrontal cortex of model mice with post-traumatic stress disorder
Jixin LI ; Min HU ; Yuanyuan HU ; Yao MENG ; Guiqing ZHANG
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(2):97-103
Objective:To investigate changes in behavior and hippocampal and prefrontal cortical myelin basic protein(MBP) in model mice with post-traumatic stress disorder(PTSD).Methods:Thirty-two clean-grade male C57BL/6J mice were randomly divided into control group, PTSD 3 d group, PTSD 7 d group and PTSD 14 d group based on matching body mass, with 8 mice in each group. The mice in PTSD 3 d, 7 d and 14 d groups were decapitated at 3 d, 7 d, and 14 d after modeling.The PTSD mouse model was established through conditioned foot shock and single prolonged stress. Anxious- and depressive-like behaviors of mice were assessed by the open field test(OFT). The mouse step-through passive avoidance experiment was used for electric shock training and learning and memory retention. Myelin morphology alterations in the hippocampus and prefrontal cortex of the mouse were examined via myelin staining.The expression levels of MBP were quantified using Western blot and immunohistochemical staining techniques. All experimental data were analyzed and visualized using GraphPad Prism 8.0.2 and SPSS 25.0, the multi groups comparison of behavioral and molecular indicator data was conducted by one-way ANOVA, and the correlation between MBP relative protein expression level and behavioral indicators was analyzed by Pearson correlation analysis.Results:(1) Behavioral results: in OFT, there were significant differences in total distance, average speed, time of stationary and times of entering the central area among all groups( F=16.72, 16.74, 7.37, 5.93, all P<0.05).The total distance and the average speed time of PTSD 3 d, 7 d, 14 d group were all lower than those in control group(all P<0.05).In the mouse step-through passive avoidance experiment, significant differences were observed across all groups in terms of total distance traveled, average speed, dark box entries, and activity time( F=52.78, 55.47, 9.07, 24.88, all P<0.05).All the indexes of PTSD 3 d group and PTSD 7 d group were all higher than those in control group and PTSD 14 d group(all P<0.05).(2)Myelin staining revealed statistically significant differences in the myelin staining areas of the hippocampal CA1 region and the prefrontal cortex across all groups( F=6.67, 5.77, all P<0.05). The stained myelin area in the CA1 region of the hippocampus in the PTSD 3 d group((123.30±11.62)μm 2)was significantly lower compared to the control group((153.00±2.61)μm 2)( P<0.05). The stained myelin area in the prefrontal cortex of the PTSD 3 d group((119.50±9.26)μm 2)was significantly lower compared to that in the control group((154.80±12.40)μm 2)( P<0.05). (3) Western blot results demonstrated significant variations in the expression levels of myelin basic protein (MBP) within the hippocampus and prefrontal cortex across all experimental groups ( F=10.15, 5.28, all P<0.05). The expression levels of MBP in the hippocampal tissue of the PTSD 3 d group (0.89±0.07), PTSD 7 d group (0.90±0.14), and PTSD 14 d group (0.85±0.13) were significantly lower compared to those in the control group(1.17±0.02)(all P<0.05). The expression levels of MBP protein in the prefrontal cortex of the PTSD 3 d group(0.73±0.16) and PTSD 7 d group (0.70±0.12)were significantly lower compared to those in the control group (0.94±0.04)(all P<0.05). (4) Immunohistochemical staining revealed significant variations in the number of MBP-positive cells within the hippocampal CA1 region and the prefrontal cortex across all groups ( F=39.32, 21.81, both P<0.05). The quantity of MBP-positive cells in the hippocampal tissue of mice in the PTSD 3 d group((187.10±1.12)/mm 2)and PTSD 7 d group((193.10±2.18) /mm 2)was significantly reduced compared to the control group((204.80±3.25)/mm 2)(all P<0.05). The quantity of MBP-positive cells in the prefrontal cortex of the PTSD 7 d group((183.90±1.71)/mm 2) was significantly reduced compared to the control group((191.60±1.04) /mm 2)( P<0.05). Conclusion:The PTSD model mice showed anxious- and depression-like behavior, impaired learning and memory ability, and myelin damage in the hippocampus and prefrontal cortex.
7.Expression of m6A-related proteins in mice with PTSD-like behavior improved by sertraline hydrochloride treatment
Jiaying LU ; Luodong YANG ; Min HU ; Wenlong XING ; Haiteng CUI ; Guiqing ZHANG
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(11):961-968
Objective:To explore the expression changes of N6-methyladenosine (m6A)-related proteins in the hippocampus of mice with post traumatic stress disorder (PTSD)-like behavior and the therapeutic effects of sertraline hydrochloride.Methods:Male C57BL/6J mice aged 4-6 weeks were selected to establish a PTSD model using a single prolonged stress and foot shock stimulation. A total of 24 mice were randomly divided into the control group, model group, and sertraline group using a random number table, with 8 mice in each group. Mice in the sertraline group were intraperitoneally injected with sertraline hydrochloride (15 mg/kg, once daily) 24 h after PTSD modelling, continuing for 14 days. Mice in the control group and model group were injected with an equal volume of 0.9% NaCl solution (once daily, for 14 days). The anxiety, despair, and learning and memory functions of the mice were assessed using the open field test, Y-maze test, and forced swimming test. Western blot was performed to measure the protein expression levels of methyltransferase-like protein 3 (METTL3), fat mass and obesity-associated gene (FTO), ALKB homolog 5 (ALKBH5), Wilms tumour 1 associating protein (WTAP), and methyltransferase-like protein 14 (METTL14) in the hippocampus. Immunofluorescence was used to detect the expression levels of METTL3, FTO, and ALKBH5 in the hippocampus. Statistical analysis was performed using SPSS 26.0 and GraphPad Prism 9.0.Comparisons between two groups were conducted using independent samples t-test, while comparisons among three groups were performed using one-way analysis of variance (ANOVA) or Kruskal-Wallis H test, followed by pairwise comparisons using LSD test. Results:(1) Behavioral results showed that the total distance travelled in the central area ( F=9.231, P<0.05) and the time spent in the central area ( H=8.045, P<0.05) showed statistically significant differences among the control, model, and sertraline groups. Mice in the control and sertraline groups travelled a greater distance((332.68±121.17)cm, (248.56±40.21)cm) and spent more time(24.98(23.08, 26.71)s, 22.52(18.86, 26.20)s) in the central area than those in the model group((131.66±84.90)cm, 9.14(6.56, 18.53)s) (all P<0.05). In the forced swimming test, the number of resting episodes ( F=16.882, P<0.05) and the duration of rest ( H=12.285, P<0.05) differed significantly among the three groups. Mice in the control group ((19.14±8.30) counts, 30.21 (18.98, 52.62) s) and the sertraline group ((17.63±8.14) counts, 25.90 (16.78, 37.56) s) had fewer resting episodes and shorter resting durations compared to those in the model group ((37.75±6.47) counts, 83.37 (64.62, 124.42) s) (all P<0.05). The percentage of alternations in the Y-maze experiment showed significant statistical differences among the three groups( F=6.844, P<0.05). Mice in the control group ((51.33±11.49)%) and the sertraline group ((48.24±3.10)%) exhibited a higher percentage of alternations than that in the model group ((36.70±8.15)%) ( P<0.05). (2) Western blot results showed that the protein expression levels of METTL3, FTO, and ALKBH5 in the hippocampal tissue of the three groups showed significant differences ( F=10.263, 9.010, 6.950, all P<0.05). The METTL3 and FTO protein expression levels in the hippocampus in the control group (0.85±0.07, 0.86±0.04) and the sertraline group (0.93±0.06, 0.95±0.13) were higher than those in the model group (0.74±0.02, 0.68±0.04) (all P<0.05). However, the ALKBH5 protein expression levels in the control group (0.93±0.08) and the sertraline group (0.87±0.13) were lower than that in the model group (1.13±0.04) (both P<0.05). (3) Immunofluorescence results showed that the expression levels of METTL3, FTO, and ALKBH5 proteins in the hippocampal tissue of the three groups showed significant statistical differences ( F=37.912, 62.659, 54.417, all P<0.05). The expression levels of METTL3 and FTO in the hippocampus in the control group (14.03±0.32, 13.85±0.28) and the sertraline group (17.94±0.29, 10.52±0.66) were higher than those in the model group (11.67±1.48, 8.70±0.68) (all P<0.05). The expression levels of ALKBH5 in the control group (12.94±0.38) and the sertraline group (13.30±0.93) were lower than that in the model group (19.24±1.03) (both P<0.05). Conclusion:The expression of m6A-related proteins in the hippocampus of PTSD-like mice is altered. Sertraline treatment can significantly regulate the expression of these proteins and improve anxiety, despair, and learning and memory impairments in the PTSD-like mice.
8.Changes in myelin basic protein expression in the hippocampus and prefrontal cortex of model mice with post-traumatic stress disorder
Jixin LI ; Min HU ; Yuanyuan HU ; Yao MENG ; Guiqing ZHANG
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(2):97-103
Objective:To investigate changes in behavior and hippocampal and prefrontal cortical myelin basic protein(MBP) in model mice with post-traumatic stress disorder(PTSD).Methods:Thirty-two clean-grade male C57BL/6J mice were randomly divided into control group, PTSD 3 d group, PTSD 7 d group and PTSD 14 d group based on matching body mass, with 8 mice in each group. The mice in PTSD 3 d, 7 d and 14 d groups were decapitated at 3 d, 7 d, and 14 d after modeling.The PTSD mouse model was established through conditioned foot shock and single prolonged stress. Anxious- and depressive-like behaviors of mice were assessed by the open field test(OFT). The mouse step-through passive avoidance experiment was used for electric shock training and learning and memory retention. Myelin morphology alterations in the hippocampus and prefrontal cortex of the mouse were examined via myelin staining.The expression levels of MBP were quantified using Western blot and immunohistochemical staining techniques. All experimental data were analyzed and visualized using GraphPad Prism 8.0.2 and SPSS 25.0, the multi groups comparison of behavioral and molecular indicator data was conducted by one-way ANOVA, and the correlation between MBP relative protein expression level and behavioral indicators was analyzed by Pearson correlation analysis.Results:(1) Behavioral results: in OFT, there were significant differences in total distance, average speed, time of stationary and times of entering the central area among all groups( F=16.72, 16.74, 7.37, 5.93, all P<0.05).The total distance and the average speed time of PTSD 3 d, 7 d, 14 d group were all lower than those in control group(all P<0.05).In the mouse step-through passive avoidance experiment, significant differences were observed across all groups in terms of total distance traveled, average speed, dark box entries, and activity time( F=52.78, 55.47, 9.07, 24.88, all P<0.05).All the indexes of PTSD 3 d group and PTSD 7 d group were all higher than those in control group and PTSD 14 d group(all P<0.05).(2)Myelin staining revealed statistically significant differences in the myelin staining areas of the hippocampal CA1 region and the prefrontal cortex across all groups( F=6.67, 5.77, all P<0.05). The stained myelin area in the CA1 region of the hippocampus in the PTSD 3 d group((123.30±11.62)μm 2)was significantly lower compared to the control group((153.00±2.61)μm 2)( P<0.05). The stained myelin area in the prefrontal cortex of the PTSD 3 d group((119.50±9.26)μm 2)was significantly lower compared to that in the control group((154.80±12.40)μm 2)( P<0.05). (3) Western blot results demonstrated significant variations in the expression levels of myelin basic protein (MBP) within the hippocampus and prefrontal cortex across all experimental groups ( F=10.15, 5.28, all P<0.05). The expression levels of MBP in the hippocampal tissue of the PTSD 3 d group (0.89±0.07), PTSD 7 d group (0.90±0.14), and PTSD 14 d group (0.85±0.13) were significantly lower compared to those in the control group(1.17±0.02)(all P<0.05). The expression levels of MBP protein in the prefrontal cortex of the PTSD 3 d group(0.73±0.16) and PTSD 7 d group (0.70±0.12)were significantly lower compared to those in the control group (0.94±0.04)(all P<0.05). (4) Immunohistochemical staining revealed significant variations in the number of MBP-positive cells within the hippocampal CA1 region and the prefrontal cortex across all groups ( F=39.32, 21.81, both P<0.05). The quantity of MBP-positive cells in the hippocampal tissue of mice in the PTSD 3 d group((187.10±1.12)/mm 2)and PTSD 7 d group((193.10±2.18) /mm 2)was significantly reduced compared to the control group((204.80±3.25)/mm 2)(all P<0.05). The quantity of MBP-positive cells in the prefrontal cortex of the PTSD 7 d group((183.90±1.71)/mm 2) was significantly reduced compared to the control group((191.60±1.04) /mm 2)( P<0.05). Conclusion:The PTSD model mice showed anxious- and depression-like behavior, impaired learning and memory ability, and myelin damage in the hippocampus and prefrontal cortex.
9.Expression of m6A-related proteins in mice with PTSD-like behavior improved by sertraline hydrochloride treatment
Jiaying LU ; Luodong YANG ; Min HU ; Wenlong XING ; Haiteng CUI ; Guiqing ZHANG
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(11):961-968
Objective:To explore the expression changes of N6-methyladenosine (m6A)-related proteins in the hippocampus of mice with post traumatic stress disorder (PTSD)-like behavior and the therapeutic effects of sertraline hydrochloride.Methods:Male C57BL/6J mice aged 4-6 weeks were selected to establish a PTSD model using a single prolonged stress and foot shock stimulation. A total of 24 mice were randomly divided into the control group, model group, and sertraline group using a random number table, with 8 mice in each group. Mice in the sertraline group were intraperitoneally injected with sertraline hydrochloride (15 mg/kg, once daily) 24 h after PTSD modelling, continuing for 14 days. Mice in the control group and model group were injected with an equal volume of 0.9% NaCl solution (once daily, for 14 days). The anxiety, despair, and learning and memory functions of the mice were assessed using the open field test, Y-maze test, and forced swimming test. Western blot was performed to measure the protein expression levels of methyltransferase-like protein 3 (METTL3), fat mass and obesity-associated gene (FTO), ALKB homolog 5 (ALKBH5), Wilms tumour 1 associating protein (WTAP), and methyltransferase-like protein 14 (METTL14) in the hippocampus. Immunofluorescence was used to detect the expression levels of METTL3, FTO, and ALKBH5 in the hippocampus. Statistical analysis was performed using SPSS 26.0 and GraphPad Prism 9.0.Comparisons between two groups were conducted using independent samples t-test, while comparisons among three groups were performed using one-way analysis of variance (ANOVA) or Kruskal-Wallis H test, followed by pairwise comparisons using LSD test. Results:(1) Behavioral results showed that the total distance travelled in the central area ( F=9.231, P<0.05) and the time spent in the central area ( H=8.045, P<0.05) showed statistically significant differences among the control, model, and sertraline groups. Mice in the control and sertraline groups travelled a greater distance((332.68±121.17)cm, (248.56±40.21)cm) and spent more time(24.98(23.08, 26.71)s, 22.52(18.86, 26.20)s) in the central area than those in the model group((131.66±84.90)cm, 9.14(6.56, 18.53)s) (all P<0.05). In the forced swimming test, the number of resting episodes ( F=16.882, P<0.05) and the duration of rest ( H=12.285, P<0.05) differed significantly among the three groups. Mice in the control group ((19.14±8.30) counts, 30.21 (18.98, 52.62) s) and the sertraline group ((17.63±8.14) counts, 25.90 (16.78, 37.56) s) had fewer resting episodes and shorter resting durations compared to those in the model group ((37.75±6.47) counts, 83.37 (64.62, 124.42) s) (all P<0.05). The percentage of alternations in the Y-maze experiment showed significant statistical differences among the three groups( F=6.844, P<0.05). Mice in the control group ((51.33±11.49)%) and the sertraline group ((48.24±3.10)%) exhibited a higher percentage of alternations than that in the model group ((36.70±8.15)%) ( P<0.05). (2) Western blot results showed that the protein expression levels of METTL3, FTO, and ALKBH5 in the hippocampal tissue of the three groups showed significant differences ( F=10.263, 9.010, 6.950, all P<0.05). The METTL3 and FTO protein expression levels in the hippocampus in the control group (0.85±0.07, 0.86±0.04) and the sertraline group (0.93±0.06, 0.95±0.13) were higher than those in the model group (0.74±0.02, 0.68±0.04) (all P<0.05). However, the ALKBH5 protein expression levels in the control group (0.93±0.08) and the sertraline group (0.87±0.13) were lower than that in the model group (1.13±0.04) (both P<0.05). (3) Immunofluorescence results showed that the expression levels of METTL3, FTO, and ALKBH5 proteins in the hippocampal tissue of the three groups showed significant statistical differences ( F=37.912, 62.659, 54.417, all P<0.05). The expression levels of METTL3 and FTO in the hippocampus in the control group (14.03±0.32, 13.85±0.28) and the sertraline group (17.94±0.29, 10.52±0.66) were higher than those in the model group (11.67±1.48, 8.70±0.68) (all P<0.05). The expression levels of ALKBH5 in the control group (12.94±0.38) and the sertraline group (13.30±0.93) were lower than that in the model group (19.24±1.03) (both P<0.05). Conclusion:The expression of m6A-related proteins in the hippocampus of PTSD-like mice is altered. Sertraline treatment can significantly regulate the expression of these proteins and improve anxiety, despair, and learning and memory impairments in the PTSD-like mice.
10.Changes in brain activity in patients with post-traumatic stress disorder two months after the traumatic event
Luodong YANG ; Haohao LI ; Yao MENG ; Min HU ; Wenlong XING ; Liang JIANG ; Guiqing ZHANG
Chinese Mental Health Journal 2025;39(4):301-307
Objective:To explore changes in brain activity in patients with post-traumatic stress disorder(PTSD).Methods:A total of 40 participants involved in car accidents were included,and functional magnetic reso-nance imaging(fMRI)scans were collected within one week.Anxiety,depression,and personality assessments were conducted with the Hamilton Anxiety Scale(HAMA),Hamilton Depression Scale(HAMD),and Eysenck Person-ality Scale for Adult(EPQ).After two months,a second fMRI scan was conducted,and a PTSD diagnosis was made.Participants were divided into a trauma-exposed group(n=23)and a PTSD group(n=17)based on wheth-er they developed PTSD.Changes in brain functional activity between the trauma-exposed group and the PTSD group were compared using the percentage of amplitude fluctuation(perAF)method.Results:Compared to the trauma-exposed group,the PTSD group showed a decreased perAF value in the left hippocampus at 1 week,and de-creased perAF values in the right mid-cingulate gyrus and left postcentral gyrus at 2 months(P<0.05).When comparing the PTSD group at different times,the perAF values in the left middle temporal gyrus and left medial su-perior frontal gyrus decreased at 2 months(P<0.05).Correlation analysis revealed that PCL-5 scores were posi-tively correlated with EPQ Psychoticism(r=0.32,P=0.041),HAMA(r=0.35,P<0.05),and HAMD(r=0.34,P<0.05).Regression analysis found that higher scores of EPQ psychoticism(OR=11.79)and HAMA(OR=1.62)were risk factors for post-accident PTSD,while higher scores of EPQ extraversion(OR=0.32)were pro-tective factors.Conclusion:It suggests that patients with post-traumatic stress disorder may show decreased activity in the right middle cingulate cortex,left postcentral gyrus,left middle temporal gyrus,and left medial superior fron-tal gyrus within two months after the traumatic event.


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