1.Clinical study of intracranial hypotension targeted body posture combined with pharmacotherapy in the treatment of chronic subdural hematoma
Jiayu CHEN ; Zhe WANG ; Di ZANG ; Ruizhe ZHENG ; Xiangru YE ; Zengxin QI ; Zeyu XU ; Zhiqiang LI ; Chengfeng SUN ; Liangjun SHEN ; Luoping SHENG ; Fulin XU ; Ruyong YE ; Kaiyu ZHOU ; Weijun TANG ; Yueqing HU ; Dapeng SHI ; Yuquan WANG ; Xizhen WU ; Ying WANG ; Qilin ZHANG ; Feili LIU ; Guo YU ; Yiping LU ; Yirui SUN ; Ning ZHANG ; Feng HUANG ; Xialong GU ; Han ZHANG ; Jian DING ; Yongyan BI ; Haolan DU ; Jing ZHANG ; Hailong JI ; Ding DING ; Wei ZHANG ; Xuehai WU
Chinese Journal of Surgery 2025;63(3):212-218
Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.
2.Analysis of factors influencing postoperative pathological upgrading in prostate cancer with target biopsy Gleason score 3 + 3 and development of a predictive model
Rongjie SHI ; Lai DONG ; Zhiyi SHEN ; Kaiyu ZHANG ; Chenglong ZHANG ; Yamin WANG ; Ruizhe ZHAO ; Shangqian WANG ; Gong CHENG ; Lixin HUA
Chinese Journal of Urology 2025;46(9):684-690
Objective:To explore the influencing factors for pathological upgrading in prostate cancer patients with a Gleason score of 3 + 3 undergoing targeted biopsy,and to establish a nomogram prediction model.Methods:A retrospective analysis was conducted on 191 patients with localized prostate cancer diagnosed with a Gleason score of 3 + 3 through targeted biopsies at the First Affiliated Hospital of Nanjing Medical University from January 2020 to June 2024. The age of the patients was 67(61,73)years,with prostate-specific antigen(PSA)level of 7.44(5.53,10.19)ng/ml,prostate volume of 35.64(26.59,48.97)ml,and PSA density(PSAD)of 0.20(0.14,0.31)ng/ml 2. Among them,61 cases(31.94%)had a Prostate Imaging Reporting and Data System(PI-RADS)score of 3,104 cases(54.45%)had a score of 4,and 26 cases(13.61%)had a score of 5. The diameter of the main lesion was 10.75(7.86,14.00)mm. The lesions were located in the peripheral zone in 78 cases(40.84%),the transition zone in 99 cases(51.83%),and the anterior fibromuscular stroma in 14 cases(7.33%). The lesions were found at the apex in 56 cases(29.32%),in the body in 120 cases(62.83%),and at the base in 15 cases(7.85%). MRI revealed only one lesion with a PI-RADS score ≥ 3 in 131 cases,two suspected lesions in 43 cases,three suspected lesions in 12 cases,and four suspected lesions in 5 cases. Systematic biopsy was positive in 121 cases(63.4%)and negative in 70 cases(36.6%). The lesions were confined to the left lobe in 63 cases(32.98%),right lobe in 68 cases(35.60%),and involved both lobes in 60 cases(31.41%). The interval between biopsy and surgery was 9.0(7.0,14.0)days. Univariate analyses were performed using Mann-Whitney U tests or χ2 tests,and multivariate logistic regression was used to identify independent predictors of pathological upgrading. A nomogram model was constructed based on these independent predictors. The model’s discriminative ability was assessed using the area under the receiver operating characteristic(ROC)curve(AUC),and internal validation of the model’s consistency was conducted using the bootstrap resampling method. Decision curve analysis(DCA)was performed to assess clinical utility. Results:Among the 191 cases,60(31.4%)had no pathological upgrading after surgery,while 131(68.6%)showed upgrading. Univariate analysis showed that the maximum diameter of the main lesion[9.0(6.0,13.2)mm vs. 11.0(8.4,14.0)mm],number of suspicious lesions on MRI[1.0(1.0,1.0)vs. 1.0(1.0,2.0)],number of positive systematic biopsy cores[1.0(0,2.0)vs. 1.0(0,3.0)],percentage of positive systematic biopsy cores[0.08(0,0.17)vs. 0.12(0,0.25)],number of positive targeted biopsy cores[2.0(1.0,3.0)vs. 3.0(1.0,4.0)],percentage of positive targeted biopsy cores[0.37(0.24,0.75)vs. 0.50(0.38,0.85)],level of the index lesion,location of the index lesion,and PI-RADS score were associated with pathological upgrading( P < 0.05). Multivariate logistic regression analysis showed that PI-RADS score 4( OR = 5.88,95% CI 2.41 - 14.35),number of suspicious lesions on MRI( OR = 4.15,95% CI 1.88 - 9.17),location of the index lesion in the transition zone( OR = 6.86,95% CI 2.81 - 16.73),and percentage of positive targeted biopsy cores( OR = 4.37,95% CI 1.38 - 14.90)were independent risk factors for pathological upgrading( P < 0.05). The nomogram model constructed using these predictors had an AUC of 0.845. Internal validation using the Bootstrap method yielded an AUC value of 0.812,indicating high predictive accuracy of the model. The calibration curve indicated good calibration. Decision curve analysis showed that the threshold range for net benefit in the model was between 12% - 100%. Conclusions:The PI-RADS score 4,the number of lesions with PI-RADS ≥ 3,the location of the main lesion in the transition zone,and the percentage of positive needles in targeted biopsy are independent risk factors for pathological upgrading from Gleason score 3 + 3. The nomogram model constructed from these factors demonstrates good predictive performance and provides a reference for clinical decision-making.
3.The mediating role of reduced amygdala subregion volume between childhood trauma and depression severity in patients with major depressive disorder
Azi SHEN ; Wenyue GONG ; Yinghong HUANG ; Yiwen WANG ; Qiudong XIA ; Kaiyu SHI ; Qinghua ZHAI ; Rui YAN ; Qing LU ; Zhijian YAO
Chinese Journal of Psychiatry 2025;58(5):356-364
Objective:This study aims to explore the independent and interactive effects of childhood trauma (CT) and major depressive disorder (MDD) on amygdala subregion volumes and to examine whether volumetric changes in these subregions mediate the relationship between CT and depressive severity.Methods:A total of 129 MDD patients and 127 age- and sex-matched healthy controls were recruited from Nanjing Brain Hospital between October 2022 and November 2024. All participants underwent 3D-T 1 weighted MRI scans,and amygdala subregions were segmented using the FreeSurfer software. Depressive and anxiety symptoms were assessed with the 17-item Hamilton Depression Rating Scale (HAMD 17) and the Hamilton Anxiety Scale (HAMA),respectively. Childhood trauma exposure was evaluated via the Childhood Trauma Questionnaire (CTQ). Generalized linear models (GLM) were applied to analyze the main and interactive effects of MDD diagnosis (depression/healthy controls) and CT (presence/absence),adjusting for age,estimated intracranial volume,sex,medication history,and education years. Partial correlation and mediation analyses were conducted to explore associations between amygdala subregion volumes and clinical measures in MDD patients. Results:MDD diagnosis was independently associated with increased volumes in the right central nucleus ( Wald χ2=9.09, P=0.026) and medial nucleus ( Wald χ2=10.08, P=0.026). CT exposure was independently associated with reduced volumes in the right central nucleus ( Wald χ2=7.99, P=0.047) and medial nucleus ( Wald χ2=9.20, P=0.047). No significant interaction effects between MDD and CT were observed in any amygdala subregion. Mediation analysis revealed that reduced right medial nucleus volume partially mediated the relationship between total CTQ scores and depressive severity (proportion mediated: 26.69%,95% CI=0.002-0.060) and mediated the association between emotional neglect and depressive severity (proportion mediated: 26.75%,95% CI=0.006-0.150). Such mediating effects were not found for the right central nucleus. Conclusion:CT and MDD exhibit divergent patterns of influence on amygdala subregions. CT is linked to volumetric reductions,whereas MDD is associated with volumetric enlargement. Reduced volume of the right medial nucleus mediates the relationship between CT and depression severity.
4.Analysis of factors influencing postoperative pathological upgrading in prostate cancer with target biopsy Gleason score 3 + 3 and development of a predictive model
Rongjie SHI ; Lai DONG ; Zhiyi SHEN ; Kaiyu ZHANG ; Chenglong ZHANG ; Yamin WANG ; Ruizhe ZHAO ; Shangqian WANG ; Gong CHENG ; Lixin HUA
Chinese Journal of Urology 2025;46(9):684-690
Objective:To explore the influencing factors for pathological upgrading in prostate cancer patients with a Gleason score of 3 + 3 undergoing targeted biopsy,and to establish a nomogram prediction model.Methods:A retrospective analysis was conducted on 191 patients with localized prostate cancer diagnosed with a Gleason score of 3 + 3 through targeted biopsies at the First Affiliated Hospital of Nanjing Medical University from January 2020 to June 2024. The age of the patients was 67(61,73)years,with prostate-specific antigen(PSA)level of 7.44(5.53,10.19)ng/ml,prostate volume of 35.64(26.59,48.97)ml,and PSA density(PSAD)of 0.20(0.14,0.31)ng/ml 2. Among them,61 cases(31.94%)had a Prostate Imaging Reporting and Data System(PI-RADS)score of 3,104 cases(54.45%)had a score of 4,and 26 cases(13.61%)had a score of 5. The diameter of the main lesion was 10.75(7.86,14.00)mm. The lesions were located in the peripheral zone in 78 cases(40.84%),the transition zone in 99 cases(51.83%),and the anterior fibromuscular stroma in 14 cases(7.33%). The lesions were found at the apex in 56 cases(29.32%),in the body in 120 cases(62.83%),and at the base in 15 cases(7.85%). MRI revealed only one lesion with a PI-RADS score ≥ 3 in 131 cases,two suspected lesions in 43 cases,three suspected lesions in 12 cases,and four suspected lesions in 5 cases. Systematic biopsy was positive in 121 cases(63.4%)and negative in 70 cases(36.6%). The lesions were confined to the left lobe in 63 cases(32.98%),right lobe in 68 cases(35.60%),and involved both lobes in 60 cases(31.41%). The interval between biopsy and surgery was 9.0(7.0,14.0)days. Univariate analyses were performed using Mann-Whitney U tests or χ2 tests,and multivariate logistic regression was used to identify independent predictors of pathological upgrading. A nomogram model was constructed based on these independent predictors. The model’s discriminative ability was assessed using the area under the receiver operating characteristic(ROC)curve(AUC),and internal validation of the model’s consistency was conducted using the bootstrap resampling method. Decision curve analysis(DCA)was performed to assess clinical utility. Results:Among the 191 cases,60(31.4%)had no pathological upgrading after surgery,while 131(68.6%)showed upgrading. Univariate analysis showed that the maximum diameter of the main lesion[9.0(6.0,13.2)mm vs. 11.0(8.4,14.0)mm],number of suspicious lesions on MRI[1.0(1.0,1.0)vs. 1.0(1.0,2.0)],number of positive systematic biopsy cores[1.0(0,2.0)vs. 1.0(0,3.0)],percentage of positive systematic biopsy cores[0.08(0,0.17)vs. 0.12(0,0.25)],number of positive targeted biopsy cores[2.0(1.0,3.0)vs. 3.0(1.0,4.0)],percentage of positive targeted biopsy cores[0.37(0.24,0.75)vs. 0.50(0.38,0.85)],level of the index lesion,location of the index lesion,and PI-RADS score were associated with pathological upgrading( P < 0.05). Multivariate logistic regression analysis showed that PI-RADS score 4( OR = 5.88,95% CI 2.41 - 14.35),number of suspicious lesions on MRI( OR = 4.15,95% CI 1.88 - 9.17),location of the index lesion in the transition zone( OR = 6.86,95% CI 2.81 - 16.73),and percentage of positive targeted biopsy cores( OR = 4.37,95% CI 1.38 - 14.90)were independent risk factors for pathological upgrading( P < 0.05). The nomogram model constructed using these predictors had an AUC of 0.845. Internal validation using the Bootstrap method yielded an AUC value of 0.812,indicating high predictive accuracy of the model. The calibration curve indicated good calibration. Decision curve analysis showed that the threshold range for net benefit in the model was between 12% - 100%. Conclusions:The PI-RADS score 4,the number of lesions with PI-RADS ≥ 3,the location of the main lesion in the transition zone,and the percentage of positive needles in targeted biopsy are independent risk factors for pathological upgrading from Gleason score 3 + 3. The nomogram model constructed from these factors demonstrates good predictive performance and provides a reference for clinical decision-making.
5.The mediating role of reduced amygdala subregion volume between childhood trauma and depression severity in patients with major depressive disorder
Azi SHEN ; Wenyue GONG ; Yinghong HUANG ; Yiwen WANG ; Qiudong XIA ; Kaiyu SHI ; Qinghua ZHAI ; Rui YAN ; Qing LU ; Zhijian YAO
Chinese Journal of Psychiatry 2025;58(5):356-364
Objective:This study aims to explore the independent and interactive effects of childhood trauma (CT) and major depressive disorder (MDD) on amygdala subregion volumes and to examine whether volumetric changes in these subregions mediate the relationship between CT and depressive severity.Methods:A total of 129 MDD patients and 127 age- and sex-matched healthy controls were recruited from Nanjing Brain Hospital between October 2022 and November 2024. All participants underwent 3D-T 1 weighted MRI scans,and amygdala subregions were segmented using the FreeSurfer software. Depressive and anxiety symptoms were assessed with the 17-item Hamilton Depression Rating Scale (HAMD 17) and the Hamilton Anxiety Scale (HAMA),respectively. Childhood trauma exposure was evaluated via the Childhood Trauma Questionnaire (CTQ). Generalized linear models (GLM) were applied to analyze the main and interactive effects of MDD diagnosis (depression/healthy controls) and CT (presence/absence),adjusting for age,estimated intracranial volume,sex,medication history,and education years. Partial correlation and mediation analyses were conducted to explore associations between amygdala subregion volumes and clinical measures in MDD patients. Results:MDD diagnosis was independently associated with increased volumes in the right central nucleus ( Wald χ2=9.09, P=0.026) and medial nucleus ( Wald χ2=10.08, P=0.026). CT exposure was independently associated with reduced volumes in the right central nucleus ( Wald χ2=7.99, P=0.047) and medial nucleus ( Wald χ2=9.20, P=0.047). No significant interaction effects between MDD and CT were observed in any amygdala subregion. Mediation analysis revealed that reduced right medial nucleus volume partially mediated the relationship between total CTQ scores and depressive severity (proportion mediated: 26.69%,95% CI=0.002-0.060) and mediated the association between emotional neglect and depressive severity (proportion mediated: 26.75%,95% CI=0.006-0.150). Such mediating effects were not found for the right central nucleus. Conclusion:CT and MDD exhibit divergent patterns of influence on amygdala subregions. CT is linked to volumetric reductions,whereas MDD is associated with volumetric enlargement. Reduced volume of the right medial nucleus mediates the relationship between CT and depression severity.
6.Clinical study of intracranial hypotension targeted body posture combined with pharmacotherapy in the treatment of chronic subdural hematoma
Jiayu CHEN ; Zhe WANG ; Di ZANG ; Ruizhe ZHENG ; Xiangru YE ; Zengxin QI ; Zeyu XU ; Zhiqiang LI ; Chengfeng SUN ; Liangjun SHEN ; Luoping SHENG ; Fulin XU ; Ruyong YE ; Kaiyu ZHOU ; Weijun TANG ; Yueqing HU ; Dapeng SHI ; Yuquan WANG ; Xizhen WU ; Ying WANG ; Qilin ZHANG ; Feili LIU ; Guo YU ; Yiping LU ; Yirui SUN ; Ning ZHANG ; Feng HUANG ; Xialong GU ; Han ZHANG ; Jian DING ; Yongyan BI ; Haolan DU ; Jing ZHANG ; Hailong JI ; Ding DING ; Wei ZHANG ; Xuehai WU
Chinese Journal of Surgery 2025;63(3):212-218
Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.
7.The variation characteristics of Siglec-9 in pulmonary tuberculosis
Yueyue HE ; Yuejie ZHU ; Zhengwei YIN ; Juan SHI ; Kaiyu SHANG ; Tingting TIAN ; Huidong SHI ; Jianbing DING ; Fengbo ZHANG
Immunological Journal 2024;40(6):526-532
This study was performed to investigate the variation characteristics and functions of Siglec-9 immune checkpoint in pulmonary tuberculosis.R language was used for bioinformatics analysis of GSE83456 chip data.Total of 48 patients with confirmed pulmonary tuberculosis(PTB)and 46 healthy controls were included.Real-time fluorescence quantitative PCR(qRT-PCR)was used to detect the mRNA expression of Siglec-9 in peripheral blood;flow cytometry was used to detect the proportion of Siglec-9+CD4+T cells.The levels of TNF-α,IL-6,IFN-γ and IL-4 were detected by Cytometric Bead Array(CBA).Furthermore,the correlation of the proportion of Siglec-9+CD4+T cells with TNF-α and other cytokines were analyzed.Bioinformatics analysis showed that Siglec-9 was significantly increased in patients with PTB(P<0.001),and was related to TNF-α/NF-κB,IL-6/JAK/STATA3,PI3K/AKT/mTOR signal pathways.Experimental data showed that the proportion of Siglec-9+CD4+T cells was significantly increased in patients with PTB(P<0.001)and negatively correlated with the levels of TNF-α and other cytokines.In conclusion,the higher levels of Siglec-9 mRNA and Siglec-9+CD4+T cells in PTB may inhibit the function of CD4+T cells and participate in the occurrence and development of PTB.
8.Ifitm3 knockout inhibits the proliferation and differentiation of neural stem cells in mice
Kaiyu WANG ; Xuepei LEI ; Yiying HUANG ; Guiying SHI ; Hanwei YUE ; Jie WANG ; Yifan LIN ; Jiaming TANG ; Lin BAI
Acta Laboratorium Animalis Scientia Sinica 2024;32(6):691-701
Objective To establish interferon-induced transmembrane protein 3(Ifitm3)knockout mice and to explore the effects of Ifitm3 on the proliferation and differentiation of adult neural stem cells of mice(aNSCs).Methods IFITM3 knockout mice were established by the CRISPR/Cas9 method and identified by genotype identification and Western Blot.The differences between Ifitm3-knockout mice and wild-type mice were analyzed by hematoxylin-eosin(HE)staining and flow cytometry.The aNSCs of wild-type mice and Ifitm3-knockout mice were isolated and cultured,the number and size of neurospheres were detected,The ability of aNSCs to proliferate and differentiate were detected by quantitative reverse-transcription polymerase chain reaction,Western Blot,and immunofluorescence.Results Ifitm3-knockout mice were successfully established.The mice developed normally,and there were no obvious abnormalities either histopathologically or the immune system.In vitro experiments showed that Ifitm3 knockout inhibited the self-renewal potential of aNSCs,led to a decrease in the proliferation ability of aNSCs,and inhibited the differentiation of aNSCs into immature neurons and astrocytes.Conclusions This study finds that a lack of IFITM3 result in the ability of aNSCs to proliferate and differentiate decreased,IFITM3 may regulate the function of aNSCs.
9.Verification of the expression trend and interaction prediction of innate immune cells and immune-checkpoint molecules in the process of oral mucosal carcinogenesis
Kaiyu LI ; Lijuan SHI ; Linxin LIU ; Jie WANG ; Minhai NIE ; Xuqian LIU
West China Journal of Stomatology 2024;42(2):192-206
Objective This study aimed to explore the expression trends of innate immune cells and immune-checkpoint molecules validated by data calculation in the process of oral mucosal carcinogenesis,as well as to explore methods of suppressing oral mucosal carcinogenesis based on immunotherapy by predicting their interactions.Me-thods 1)The cancer genome atlas(TCGA)database comprehensively scores immune cells and immune-checkpoint molecules in the process of oral mucosal carcinogenesis and screens out intrinsic immune cells and immune-check-point molecules that interfere with tumor immune escape.2)Clinical patient blood routine data were collected for the statistical analysis of peripheral blood immune cells during the progression of oral mucosal carcinogenesis.Immune cells in peripheral blood that may affect the progression of oral mucosal carcinogenesis were screened.3)Immunohis-tochemical staining was performed on intrinsic immune cells and immune-checkpoint molecules validated based on da-ta calculation in various stages of oral mucosal carcinogenesis.4)Special staining was used to identify innate immune cells in various stages of oral mucosal carcinogenesis based on data-calculation verification.5)Survival analysis was conducted on intrinsic immune cells and immune-checkpoint molecules validated based on data calculation during the process of oral mucosal carcinogenesis.The association of intrinsic immune cells and immune-checkpoint molecules with the prognosis of oral squamous cell carcinoma was verified.Results The expression of monocytes and neutro-phils increased during the process of oral mucosal carcinogenesis.The expression of eosinophils showed a single peak trend of up and down.The expression of mast cells decreased.In the process of oral mucosal carcinogenesis,the ex-pression of the immune-checkpoint molecules cytotoxic T-lymphocyte-associated protein 4(CTLA4)and programmed cell death-ligand(PD-L1)increased.The expression trends of monocytes,neutrophils,and eosinophils were positively correlated with those of CTLA4 and PD-L1 immune-checkpoint molecules.The expression trend of mast cells was negatively correlated with the expression of CTLA4 and PD-L1.Monocytes,neutrophils,and eosinophils may pro-mote tumor immune escape mediated by CTLA4 and/or PD-L1,thereby accelerating the progression of oral mucosal carcinogenesis.Mast cells may inhibit tumor immune escape mediated by CTLA4 and/or PD-L1,delaying the progres-sion of oral mucosal carcinogenesis.Conclusion Therefore,interference with specific immune cells in innate immu-nity can regulate the expression of CTLA4 and/or PD-L1 to a certain extent,inhibit tumor immune escape,and delay the progression of oral mucosal carcinogenesis.
10.SETD5 regulates colon cancer cell migration and 5-FU sensitivity by mediating AKT1 phosphorylation
HUANG Kaiyu ; SHI Jianguo ; CHENG Yong
Chinese Journal of Cancer Biotherapy 2024;31(6):586-591
[摘 要] 目的:探讨含SET结构域蛋白5(SETD5)对结肠癌细胞增殖、迁移和对5-氟尿嘧啶(5-FU)药物敏感性的影响及机制。方法:常规培养结肠癌细胞,用Lipofectamine 2000将siSETD5-NC、si-SETD5-1~3质粒转染至HT-29细胞中,将其分为对照组(未处理)、si-SETD5-NC组、si-SETD5组和si-SETD5+SC79组,si-SETD5+SC79组HT-29细胞转染质粒的同时用10 µmol/L SC79处理。qPCR法检测NCM460、HT-29和LoVo细胞中SETD5 mRNA表达,流式细胞术、细胞划痕法、WB法和CCK-8法分别检测各组HT-29细胞的凋亡情况、迁移能力、相关蛋白的表达,以及对5-FU的敏感性。结果:SETD5 mRNA在HT-29、LoVo细胞中均呈高表达(均P<0.01)。在HT-29细胞中成功地敲减了SETD5 mRNA(P<0.01)。敲减SETD5 mRNA可明显抑制HT-29细胞的增殖活性(P<0.01)、迁移能力(P<0.01)、相关蛋白(SETD5、p-PI3K、p-AKT1、p-mTOR蛋白)的表达(均P<0.01)、促进细胞凋亡(P<0.01),且提高其对5-FU的敏感性(P<0.01),这些作用均可被AKT激活剂SC79部分阻挡(P<0.05或P<0.01)。结论:SETD5在HT-29、LoVo细胞中高表达,SETD5通过PI3K/AKT1通路促进结肠癌HT-29细胞的增殖、迁移,且降低其对5-FU的敏感性,SETD5是结肠癌临床诊断、治疗的潜在靶点。

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