1.Clinical efficacy and safety of vortioxetine as an adjuvant drug for patients with bipolar depression.
Chunxiao DAI ; Yaoyang FU ; Xuanwei LI ; Meihua LIN ; Yinbo LI ; Xiao LI ; Keke HUANG ; Chengcheng ZHOU ; Jian XIE ; Qingwei ZHAO ; Shaohua HU
Journal of Zhejiang University. Science. B 2025;26(1):26-38
OBJECTIVES:
Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial. This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression.
METHODS:
Patients with bipolar Ⅱ depression were enrolled in this prospective, two-center, randomized, 12-week pilot trial. The main indicator for assessing treatment effectiveness was a Montgomery-Asberg Depression Rating Scale (MADRS) of ≥50%. All eligible patients initially received four weeks of lurasidone monotherapy. Patients who responded well continued to receive this kind of monotherapy. However, no-response patients were randomly assigned to either valproate or vortioxetine treatment for eight weeks. By comprehensively comparing the results of MADRS over a period of 4‒12 weeks, a systematic analysis was conducted to determine whether vortioxetine could be used as an adjuvant drug for treating bipolar depression.
RESULTS:
Thirty-seven patients responded to lurasidone monotherapy, and 60 patients were randomly assigned to the valproate or vortioxetine group for eight weeks. After two weeks of combined valproate or vortioxetine treatment, the MADRS score in the vortioxetine group was significantly lower than that in the valproate group. There was no difference in the MADRS scores between the two groups at 8 and 12 weeks. The incidence of side effects did not significantly differ between the valproate and vortioxetine groups. Importantly, three patients in the vortioxetine group appeared to switch to mania or hypomania.
CONCLUSIONS
This study suggested that lurasidone combination with vortioxetine might have potential benefits to bipolar II depression in the early stage, while disease progression should be monitored closely for the risk of switching to mania.
Humans
;
Bipolar Disorder/drug therapy*
;
Vortioxetine/therapeutic use*
;
Male
;
Female
;
Middle Aged
;
Adult
;
Valproic Acid/administration & dosage*
;
Lurasidone Hydrochloride/administration & dosage*
;
Prospective Studies
;
Treatment Outcome
;
Pilot Projects
;
Drug Therapy, Combination
;
Sulfides/therapeutic use*
;
Antidepressive Agents/therapeutic use*
2.Diagnostic value of the vesical imaging-reporting and data system in bladder urothelial carcinoma with variant histology
Linjing JIANG ; Xiao YANG ; Lingkai CAI ; Qiang CAO ; Wei TIAN ; Xiaotong LIU ; Bo LIANG ; Meihua JIANG ; Gongcheng WANG ; Qiang SHAO ; Hongliang QUE ; Xuping JIANG ; Qiang LYU
Chinese Journal of Urology 2025;46(10):751-758
Objective:To evaluate the diagnostic value of the vesical imaging-reporting and data system(VI-RADS)for determining muscle invasion in variant histology urothelial carcinoma(VUC)of the bladder.Methods:A retrospective analysis was performed on the pathological and imaging data of 518 bladder cancer patients admitted to Jiangsu Province Hospital between January 2013 and January 2023. Patients were stratified into pure urothelial carcinoma(PUC)group( n = 457)and variant urothelial carcinoma(VUC)group( n = 61)based on the presence of histological variants. In the PUC group,there were 390 males(85.3%)and 67 females(14.7%),with a mean age of(66.9 ± 11.2)years. Tumor characteristics included maximum diameter ≥ 30 mm in 149(32.6%),< 30 mm in 308(67.4%),multiple tumors in 147(32.2%),solitary in 310(67.8%),pedunculated morphology in 143(31.3%)and non-pedunculated in 314(68.7%). Histological grading identified high-grade tumors in 319 patients(69.8%)and low-grade tumors in 138(30.2%). Pathological stage distribution included 191 of T a(41.8%),127 of T 1(27.8%),76 of T 2(16.6%),47 of T 3(10.3%),and 16 of T 4(3.5%)patients. The VUC group included 61 patients,comprising 51 males(83.6%)and 10 females(16.4%),with a mean age of(65.8 ± 11.4)years. Tumor characteristics were maximum diameter ≥ 30 mm in 38(62.3%),< 30 mm in 23(37.7%),multiple tumors in 16(26.2%),solitary in 45(73.8%),pedunculated morphology in 11(18.0%)and non-pedunculated in 50(82.0%). Histological grading identified high-grade tumors in 59 patients(96.7%)and low-grade tumors in 2(3.3%). Pathological stage distribution included 3 of T a(4.9%),15 of T 1(24.6%),15 of T 2(24.6%),20 of T 3(32.8%),and 8 of T 4(13.1%)patients. No statistically significant differences were found between the two groups in gender,age,or tumor multiplicity( P > 0.05). Statistically significant differences were found in pathological grade,pathological stage,maximum tumor diameter,and pedunculated morphology( P < 0.05). Furthermore,an external validation cohort of 278 bladder cancer patients treated between February 2023 and February 2024 from multiple centers(Jiangsu Provincial People’s Hospital,The First Affiliated Hospital of Zhengzhou University,Union Hospital Tongji Medical College Huazhong University of Science and Technology,Jiangsu Provincial Hospital of Traditional Chinese Medicine,Suzhou Municipal Hospital,Huaian First People’s Hospital,Yixing People’s Hospital)was retrospectively analyzed to externally validate the performance of VI-RADS scoring in predicting muscle invasion of VUC. This cohort included a PUC subgroup of 241 patients,comprising 196 males(81.3%)and 45 females(18.7%),with a mean age of(68.0 ± 10.7)years. Tumor characteristics were maximum diameter ≥ 30 mm in 85(35.3%),< 30 mm in 156(64.7%),multiple tumors in 65(27.0%),solitary in 176(73.0%),pedunculated morphology in 76(31.5%)and non-pedunculated in 165(68.5%). Histological grading identified high-grade tumors in 175 patients(72.6%)and low-grade tumors in 66(27.4%). Pathological staging comprised 107 patients of T a(44.4%),78 of T 1(32.4%),22 of T 2(9.1%),22 of T 3(9.1%),and 12 of T 4(5.0%). The VUC subgroup consisted of 37 patients,comprising 29 males(78.4%)and 8 females(21.6%),with a mean age of(70.5 ± 9.5)years. Tumor characteristics were maximum diameter ≥ 30 mm in 23(62.2%),< 30 mm in 14(37.8%),multiple tumors in 9(24.3%),solitary in 28(75.7%),pedunculated morphology in 7(18.9%)and non-pedunculated in 30(81.1%). Histological grading identified high-grade tumors in 36 patients(97.3%)and low-grade tumors in 1(2.7%). Pathological staging comprised 1 patient of T a(2.7%),9 of T 1(24.3%),7 of T 2(18.9%),19 of T 3(51.4%),and 1 of T 4(2.7%). In this validation cohort,no significant differences were found in gender,age,tumor multiplicity,or pedunculated morphology between the PUC and VUC subgroups( P > 0.05). Significant differences were observed in pathological grade,pathological stage,and maximum tumor diameter( P < 0.05). Three radiologists independently reviewed and scored the multiparametric MRI(mp-MRI)in a blinded manner. Inter-reader agreement was assessed using the weighted kappa statistic. Differences in variables between the two groups were compared using t-tests,chi-square tests,or Fisher’s exact test. The diagnostic performance of VI-RADS for muscle invasion in VUC and PUC was comprehensively evaluated using receiver operating characteristic(ROC)curves,the area under the curve(AUC),and cut-off values determined by the Youden’s index. The DeLong test was used to assess whether the diagnostic performance of VI-RADS differed between VUC and PUC. Results:In the retrospective single-center cohort,the AUC of VI-RADS for assessing muscle invasion was 0.895(95% CI 0.864?0.922)in the PUC group,with a cut-off value of > 3,and the AUC was 0.896(95% CI 0.791-0.960)in the VUC group,with a cut-off value of > 3. The difference between the two groups was not statistically significant( P = 0.986). Using a VI-RADS score > 3 as the cut-off value,the accuracy,sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)for diagnosing muscle invasion status in the PUC group were 85.8%(392/457),70.5%(98/139),92.5%(294/318),80.3%(98/122),and 87.8%(294/335),respectively. The corresponding values for the VUC group were 82.0%(50/61),76.7%(33/43),94.4%(17/18),97.1%(33/34),and 63.0%(17/27).In the retrospective multicenter cohort,the AUC of VI-RADS for assessing muscle invasion was 0.891(95% CI 0.845?0.927)in the PUC group,with a cut-off value of > 2,and the AUC was 0.898(95% CI 0.754?0.973)in the VUC group,with a cut-off value of > 3. The difference between the two groups was not statistically significant( P = 0.897). Using a VI-RADS score > 3 as the cut-off value,the accuracy,sensitivity,specificity,PPV,and NPV for diagnosing muscle invasion status in the PUC group were 85.9%(207/241),58.9%(33/56),94.1%(174/185),75.0%(33/44),and 88.3%(174/197),respectively. The corresponding values for the VUC group were 81.1%(30/37),77.8%(21/27),90.0%(9/10),95.5%(21/22),and 60.0%(9/15).In the single-center cohort,the Kappa values for inter-reader agreement in assessing muscle invasion status using VI-RADS were 0.881( P < 0.01)for the PUC group and 0.941( P < 0.01)for the VUC group among the three readers. In the multicenter cohort,the Kappa values were 0.858( P < 0.01)for the PUC group and 0.838( P < 0.01)for the VUC group. Conclusions:VI-RADS demonstrates similarly high diagnostic performance for assessing muscle invasion in both PUC and VUC,which is applicable for diagnosing muscle invasion status in VUC,and shows good inter-reader agreement.
3.Diagnostic value of the vesical imaging-reporting and data system in bladder urothelial carcinoma with variant histology
Linjing JIANG ; Xiao YANG ; Lingkai CAI ; Qiang CAO ; Wei TIAN ; Xiaotong LIU ; Bo LIANG ; Meihua JIANG ; Gongcheng WANG ; Qiang SHAO ; Hongliang QUE ; Xuping JIANG ; Qiang LYU
Chinese Journal of Urology 2025;46(10):751-758
Objective:To evaluate the diagnostic value of the vesical imaging-reporting and data system(VI-RADS)for determining muscle invasion in variant histology urothelial carcinoma(VUC)of the bladder.Methods:A retrospective analysis was performed on the pathological and imaging data of 518 bladder cancer patients admitted to Jiangsu Province Hospital between January 2013 and January 2023. Patients were stratified into pure urothelial carcinoma(PUC)group( n = 457)and variant urothelial carcinoma(VUC)group( n = 61)based on the presence of histological variants. In the PUC group,there were 390 males(85.3%)and 67 females(14.7%),with a mean age of(66.9 ± 11.2)years. Tumor characteristics included maximum diameter ≥ 30 mm in 149(32.6%),< 30 mm in 308(67.4%),multiple tumors in 147(32.2%),solitary in 310(67.8%),pedunculated morphology in 143(31.3%)and non-pedunculated in 314(68.7%). Histological grading identified high-grade tumors in 319 patients(69.8%)and low-grade tumors in 138(30.2%). Pathological stage distribution included 191 of T a(41.8%),127 of T 1(27.8%),76 of T 2(16.6%),47 of T 3(10.3%),and 16 of T 4(3.5%)patients. The VUC group included 61 patients,comprising 51 males(83.6%)and 10 females(16.4%),with a mean age of(65.8 ± 11.4)years. Tumor characteristics were maximum diameter ≥ 30 mm in 38(62.3%),< 30 mm in 23(37.7%),multiple tumors in 16(26.2%),solitary in 45(73.8%),pedunculated morphology in 11(18.0%)and non-pedunculated in 50(82.0%). Histological grading identified high-grade tumors in 59 patients(96.7%)and low-grade tumors in 2(3.3%). Pathological stage distribution included 3 of T a(4.9%),15 of T 1(24.6%),15 of T 2(24.6%),20 of T 3(32.8%),and 8 of T 4(13.1%)patients. No statistically significant differences were found between the two groups in gender,age,or tumor multiplicity( P > 0.05). Statistically significant differences were found in pathological grade,pathological stage,maximum tumor diameter,and pedunculated morphology( P < 0.05). Furthermore,an external validation cohort of 278 bladder cancer patients treated between February 2023 and February 2024 from multiple centers(Jiangsu Provincial People’s Hospital,The First Affiliated Hospital of Zhengzhou University,Union Hospital Tongji Medical College Huazhong University of Science and Technology,Jiangsu Provincial Hospital of Traditional Chinese Medicine,Suzhou Municipal Hospital,Huaian First People’s Hospital,Yixing People’s Hospital)was retrospectively analyzed to externally validate the performance of VI-RADS scoring in predicting muscle invasion of VUC. This cohort included a PUC subgroup of 241 patients,comprising 196 males(81.3%)and 45 females(18.7%),with a mean age of(68.0 ± 10.7)years. Tumor characteristics were maximum diameter ≥ 30 mm in 85(35.3%),< 30 mm in 156(64.7%),multiple tumors in 65(27.0%),solitary in 176(73.0%),pedunculated morphology in 76(31.5%)and non-pedunculated in 165(68.5%). Histological grading identified high-grade tumors in 175 patients(72.6%)and low-grade tumors in 66(27.4%). Pathological staging comprised 107 patients of T a(44.4%),78 of T 1(32.4%),22 of T 2(9.1%),22 of T 3(9.1%),and 12 of T 4(5.0%). The VUC subgroup consisted of 37 patients,comprising 29 males(78.4%)and 8 females(21.6%),with a mean age of(70.5 ± 9.5)years. Tumor characteristics were maximum diameter ≥ 30 mm in 23(62.2%),< 30 mm in 14(37.8%),multiple tumors in 9(24.3%),solitary in 28(75.7%),pedunculated morphology in 7(18.9%)and non-pedunculated in 30(81.1%). Histological grading identified high-grade tumors in 36 patients(97.3%)and low-grade tumors in 1(2.7%). Pathological staging comprised 1 patient of T a(2.7%),9 of T 1(24.3%),7 of T 2(18.9%),19 of T 3(51.4%),and 1 of T 4(2.7%). In this validation cohort,no significant differences were found in gender,age,tumor multiplicity,or pedunculated morphology between the PUC and VUC subgroups( P > 0.05). Significant differences were observed in pathological grade,pathological stage,and maximum tumor diameter( P < 0.05). Three radiologists independently reviewed and scored the multiparametric MRI(mp-MRI)in a blinded manner. Inter-reader agreement was assessed using the weighted kappa statistic. Differences in variables between the two groups were compared using t-tests,chi-square tests,or Fisher’s exact test. The diagnostic performance of VI-RADS for muscle invasion in VUC and PUC was comprehensively evaluated using receiver operating characteristic(ROC)curves,the area under the curve(AUC),and cut-off values determined by the Youden’s index. The DeLong test was used to assess whether the diagnostic performance of VI-RADS differed between VUC and PUC. Results:In the retrospective single-center cohort,the AUC of VI-RADS for assessing muscle invasion was 0.895(95% CI 0.864?0.922)in the PUC group,with a cut-off value of > 3,and the AUC was 0.896(95% CI 0.791-0.960)in the VUC group,with a cut-off value of > 3. The difference between the two groups was not statistically significant( P = 0.986). Using a VI-RADS score > 3 as the cut-off value,the accuracy,sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)for diagnosing muscle invasion status in the PUC group were 85.8%(392/457),70.5%(98/139),92.5%(294/318),80.3%(98/122),and 87.8%(294/335),respectively. The corresponding values for the VUC group were 82.0%(50/61),76.7%(33/43),94.4%(17/18),97.1%(33/34),and 63.0%(17/27).In the retrospective multicenter cohort,the AUC of VI-RADS for assessing muscle invasion was 0.891(95% CI 0.845?0.927)in the PUC group,with a cut-off value of > 2,and the AUC was 0.898(95% CI 0.754?0.973)in the VUC group,with a cut-off value of > 3. The difference between the two groups was not statistically significant( P = 0.897). Using a VI-RADS score > 3 as the cut-off value,the accuracy,sensitivity,specificity,PPV,and NPV for diagnosing muscle invasion status in the PUC group were 85.9%(207/241),58.9%(33/56),94.1%(174/185),75.0%(33/44),and 88.3%(174/197),respectively. The corresponding values for the VUC group were 81.1%(30/37),77.8%(21/27),90.0%(9/10),95.5%(21/22),and 60.0%(9/15).In the single-center cohort,the Kappa values for inter-reader agreement in assessing muscle invasion status using VI-RADS were 0.881( P < 0.01)for the PUC group and 0.941( P < 0.01)for the VUC group among the three readers. In the multicenter cohort,the Kappa values were 0.858( P < 0.01)for the PUC group and 0.838( P < 0.01)for the VUC group. Conclusions:VI-RADS demonstrates similarly high diagnostic performance for assessing muscle invasion in both PUC and VUC,which is applicable for diagnosing muscle invasion status in VUC,and shows good inter-reader agreement.
4.Effects of high-fat and low-carbohydrate diet combined with radiotherapy on tumor microenvironment of Lewis lung cancer bearing mice
Ling XIAO ; Jiahua LYU ; Meihua CHEN ; Jianming HUANG ; Ming FAN ; Hongyuan JIA ; Yudi LIU ; Yuan WANG ; Tao LI
Chinese Journal of Oncology 2024;46(8):737-745
Objective:To investigate the effect of high-fat and low-carbohydrate diet combined with radiotherapy on the tumor microenvironment of mice with lung xenografts.Methods:C57BL/6J mice were selected to establish the Lewis lung cancer model, and they were divided into the normal diet group, the high-fat and low-carbohydrate diet group, the normal diet + radiotherapy group, and the high-fat and low-carbohydrate diet + radiotherapy group, with 18 mice in each group. The mice in the normal diet group and the normal diet + radiotherapy group were fed with the normal diet with 12.11% fat for energy supply, and the mice in the high-fat and low-carbohydrate diet group and the high-fat and low-carbohydrate diet + radiotherapy group were fed with high-fat and low-carbohydratediet with 45.00% fat for energy. On the 12th to 14th days, the tumor sites of the mice in the normal diet + radiotherapy group and the high-fat and low-carbohydrate diet + radiotherapy group were treated with radiotherapy, and the irradiation dose was 24 Gy/3f. The body weight, tumor volume, blood glucose and blood ketone level, liver and kidney function, and survival status of the mice were observed and monitored. Immunohistochemical staining was used to detect the tumor-associated microangiogenesis molecule (CD34) and lymphatic endothelial hyaluronan receptor 1 (LYVE-1), Sirius staining was used to detect collagen fibers, and multiplex immunofluorescence was used to detect CD8 and programmed death-1 (PD-1). Expression of immune cell phenotypes (CD3, CD4, CD8, and Treg) was detected by flow cytometry.Results:On the 27th day after inoculation, the body weigh of the common diet group was(24.78±2.22)g, which was significantly higher than that of the common diet + radiotherapy group [(22.15±0.48)g, P=0.030] and high-fat low-carbohydrate diet + radiotherapy group [(22.02±0.77)g, P=0.031)]. On the 15th day after inoculation, the tumor volume of the high-fat and low-carbohydrate diet + radiotherapy group was (220.88±130.05) mm 3, which was significantly smaller than that of the normal diet group [(504.37±328.48) mm 3, P=0.042)] and the high-fat, low-carbohydrate diet group [(534.26±230.42) mm 3, P=0.016], but there was no statistically significant difference compared with the normal diet + radiotherapy group [(274.64±160.97) mm 3]. In the 4th week, the blood glucose values of the mice in the high-fat and low-carbohydrate diet group were lower than those in the normal diet group, with the value being (8.00±0.36) mmol/L and (9.57±0.40) mmol/L, respectively, and the difference was statistically significant ( P<0.05). The blood ketone values of the mice in the high-fat and low-carbohydrate diet group were higher than those in the normal diet group, with the value being (1.00±0.20) mmol/L and (0.63±0.06) mmol/L, respectively, in the second week. In the third week, the blood ketone values of the two groups of mice were (0.90±0.17) mmol/L and (0.70±0.10) mmol/L, respectively, and the difference was statistically significant ( P<0.05). On the 30th day after inoculation, there were no significant differences in aspartate aminotransferase, alanine aminotransferase, creatinine, and urea between the normal diet group and the high-fat, low-carbohydrate diet group (all P>0.05). The hearts, livers, spleens, lungs, and kidneys of the mice in each group had no obvious toxic changes and tumor metastasis. In the high-fat and low-carbohydrate diet + radiotherapy group, the expression of CD8 was up-regulated in the tumor tissues of mice, and the expressions of PD-1, CD34, LYVE-1, and collagen fibers were down-regulated. The proportion of CD8 + T cells in the paratumoral lymph nodes of the high-fat and low-carbohydrate diet + radiotherapy group was (25.13±0.97)%, higher than that of the normal diet group [(20.60±2.23)%, P<0.050] and the normal diet + radiotherapy group [(19.26±3.07)%, P<0.05], but there was no statistically significant difference with the high-fat and low-carbohydrate diet group [(22.03±1.75)%, P>0.05]. The proportion, of CD4 + T cells in the lymph nodes adjacent to the tumor in the normal diet + radiotherapy group (31.33±5.16)% and the high-fat and low-carbohydrate diet + radiotherapy group (30.63±1.70)% were higher than that in the normal diet group [(20.27±2.15)%, P<0.05] and the high-fat and low-carbohydrate diet group (23.70±2.62, P<0.05). Treg cells accounted for the highest (16.58±5.10)% of T cells in the para-tumor lymph nodes of the normal diet + radiotherapy group, but compared with the normal diet group, the high-fat and low-carbohydrate diet group, and the high-fat and low-carbohydrate diet + radiotherapy group, there was no statistically significant difference (all P>0.05). Conclusion:High-fat and low-carbohydrate diet plus radiotherapy can enhance the recruitment and function of immune effector cells in the tumor microenvironment, inhibit tumor microangiogenesis, and thus inhibit tumor growth.
5.Clinical Consistency Evaluation of Quetiapine Kit Based on Liquid Chromatography Tandem Mass Spectrometry Technology
LI Xuanwei ; LIN Meihua ; ZHAI You ; XU Nana ; LI Xiao ; LYU Duo ; ZHAO Qingwei ; LIU Jian
Chinese Journal of Modern Applied Pharmacy 2024;41(13):1803-1807
OBJECTIVE
To evaluate the consistency between the quetiapine LC-MS/MS kit and the laboratory-built method(reference method) in the detection results of quetiapine therapeutic drug monitoring.
METHODS
A total of 120 remaining plasma samples were collected from patients receiving quetiapine therapeutic drug monitoring from March to October in 2021. The plasma concentration of quetiapine was detected by kit and reference method respectively. The analysis of correlations and consistency was performed by outlier analysis, linear regression and Bland-Altman method.
RESULTS
No outliers were detected. The linear regression equation was Y=1.018X+4.400(r=0.998), indicating a good correlation. The Bland-Altman plot analysis showed good agreement between the two measurements.
CONCLUSION
The detection results of quetiapine LC-MS/MS kit and reference method are in good agreement. The kit can be used for clinical quetiapine treatment drug monitoring.
6.Effects of high-fat and low-carbohydrate diet combined with radiotherapy on tumor microenvironment of Lewis lung cancer bearing mice
Ling XIAO ; Jiahua LYU ; Meihua CHEN ; Jianming HUANG ; Ming FAN ; Hongyuan JIA ; Yudi LIU ; Yuan WANG ; Tao LI
Chinese Journal of Oncology 2024;46(8):737-745
Objective:To investigate the effect of high-fat and low-carbohydrate diet combined with radiotherapy on the tumor microenvironment of mice with lung xenografts.Methods:C57BL/6J mice were selected to establish the Lewis lung cancer model, and they were divided into the normal diet group, the high-fat and low-carbohydrate diet group, the normal diet + radiotherapy group, and the high-fat and low-carbohydrate diet + radiotherapy group, with 18 mice in each group. The mice in the normal diet group and the normal diet + radiotherapy group were fed with the normal diet with 12.11% fat for energy supply, and the mice in the high-fat and low-carbohydrate diet group and the high-fat and low-carbohydrate diet + radiotherapy group were fed with high-fat and low-carbohydratediet with 45.00% fat for energy. On the 12th to 14th days, the tumor sites of the mice in the normal diet + radiotherapy group and the high-fat and low-carbohydrate diet + radiotherapy group were treated with radiotherapy, and the irradiation dose was 24 Gy/3f. The body weight, tumor volume, blood glucose and blood ketone level, liver and kidney function, and survival status of the mice were observed and monitored. Immunohistochemical staining was used to detect the tumor-associated microangiogenesis molecule (CD34) and lymphatic endothelial hyaluronan receptor 1 (LYVE-1), Sirius staining was used to detect collagen fibers, and multiplex immunofluorescence was used to detect CD8 and programmed death-1 (PD-1). Expression of immune cell phenotypes (CD3, CD4, CD8, and Treg) was detected by flow cytometry.Results:On the 27th day after inoculation, the body weigh of the common diet group was(24.78±2.22)g, which was significantly higher than that of the common diet + radiotherapy group [(22.15±0.48)g, P=0.030] and high-fat low-carbohydrate diet + radiotherapy group [(22.02±0.77)g, P=0.031)]. On the 15th day after inoculation, the tumor volume of the high-fat and low-carbohydrate diet + radiotherapy group was (220.88±130.05) mm 3, which was significantly smaller than that of the normal diet group [(504.37±328.48) mm 3, P=0.042)] and the high-fat, low-carbohydrate diet group [(534.26±230.42) mm 3, P=0.016], but there was no statistically significant difference compared with the normal diet + radiotherapy group [(274.64±160.97) mm 3]. In the 4th week, the blood glucose values of the mice in the high-fat and low-carbohydrate diet group were lower than those in the normal diet group, with the value being (8.00±0.36) mmol/L and (9.57±0.40) mmol/L, respectively, and the difference was statistically significant ( P<0.05). The blood ketone values of the mice in the high-fat and low-carbohydrate diet group were higher than those in the normal diet group, with the value being (1.00±0.20) mmol/L and (0.63±0.06) mmol/L, respectively, in the second week. In the third week, the blood ketone values of the two groups of mice were (0.90±0.17) mmol/L and (0.70±0.10) mmol/L, respectively, and the difference was statistically significant ( P<0.05). On the 30th day after inoculation, there were no significant differences in aspartate aminotransferase, alanine aminotransferase, creatinine, and urea between the normal diet group and the high-fat, low-carbohydrate diet group (all P>0.05). The hearts, livers, spleens, lungs, and kidneys of the mice in each group had no obvious toxic changes and tumor metastasis. In the high-fat and low-carbohydrate diet + radiotherapy group, the expression of CD8 was up-regulated in the tumor tissues of mice, and the expressions of PD-1, CD34, LYVE-1, and collagen fibers were down-regulated. The proportion of CD8 + T cells in the paratumoral lymph nodes of the high-fat and low-carbohydrate diet + radiotherapy group was (25.13±0.97)%, higher than that of the normal diet group [(20.60±2.23)%, P<0.050] and the normal diet + radiotherapy group [(19.26±3.07)%, P<0.05], but there was no statistically significant difference with the high-fat and low-carbohydrate diet group [(22.03±1.75)%, P>0.05]. The proportion, of CD4 + T cells in the lymph nodes adjacent to the tumor in the normal diet + radiotherapy group (31.33±5.16)% and the high-fat and low-carbohydrate diet + radiotherapy group (30.63±1.70)% were higher than that in the normal diet group [(20.27±2.15)%, P<0.05] and the high-fat and low-carbohydrate diet group (23.70±2.62, P<0.05). Treg cells accounted for the highest (16.58±5.10)% of T cells in the para-tumor lymph nodes of the normal diet + radiotherapy group, but compared with the normal diet group, the high-fat and low-carbohydrate diet group, and the high-fat and low-carbohydrate diet + radiotherapy group, there was no statistically significant difference (all P>0.05). Conclusion:High-fat and low-carbohydrate diet plus radiotherapy can enhance the recruitment and function of immune effector cells in the tumor microenvironment, inhibit tumor microangiogenesis, and thus inhibit tumor growth.
7.Single-center clinical analysis of 9 049 children hospitalized for accidental injury
Cui LUO ; Meihua LIU ; Shihua LIU ; Jianxiong PENG ; Zhenghui XIAO ; Jianhui XIE ; Xinping ZHANG ; Jun QIU
Chinese Journal of Practical Nursing 2023;39(33):2579-2585
Objective:To analyze the characteristics of child cases admitted to accidental injury and provide reliable basis for the prevention of accidental injury.Methods:The clinical data of children admitted to Hunan Children′s Hospital aged 0-18 due to accidental injuries from January 1, 2018 to December 31, 2021 were retrospectively analyzed. The type of accidental injury and characteristic factors such as prognosis, gender, age, time, and location of the child were analyzed.Results:A total of 9 049 children with accidental injury were admitted, accounting for 3.72%(9 049/33 697) of the total number of hospitalized children. The top three types of accidental injuries were falls/drop (3 695 cases), foreign bodies/suffocation (2 639 cases) and traffic accidents (1 165 cases), accounting for 82.87%(7 499/9 049). There were 8 760 cases (96.81%) of improvement and recovery, 178 cases (1.97%) of disability, and 111 cases (1.23%) of unhealed/dead. Among the accidental injuries, 5 833 cases (64.46%) were boys and 3 216 cases (35.54%) were girls, and the incidence ratio was 1.81∶1. There was significant difference between boys and girls in the composition ratio of the type of accidental injury such as falls/falls, foreign bodies/suffocation, poisoning, sharp object injury, drowning ( χ2 values were 3.90-20.56, all P<0.05). Among the accidental injuries, the children aged 1 to<3 years had higher accidental injuries than the other age groups (3 263 cases, accounting for 36.06%), and the composition ratio of accidental injuries in different age groups was different ( χ2 values were 12.98-573.97, all P<0.05). Among the accidental injuries, the accidental injuries occurred in the second quarter and the third quarter were higher than those in the other two quarters (4 892 cases, accounting for 54.06%), and the composition ratio of accidental injuries such as falls/falls, foreign bodies/suffocation, burn and scald, drowning occurred in different quarters was different ( χ2 values were 10.79-18.88, all P<0.05). In the case of accidental injuries, the family was the most likely place of accidental injury, with different types of accidental injuries occurring in different places ( χ2 values were 10.08-2 186.54, all P<0.05). Conclusions:Children′s unintentional injuries are most likely to occur in boys aged 1-<3 years, and fall/fall is the main injury type. Traffic accidents are the most important unintentional injury type leading to children′s unhealed/dead. Different injury types were related to child gender, age, quarter, and place of occurrence.Due to the differences in the occurrence mechanism and injury mode of accidental injuries in different countries and regions, and the majority of accidental injuries can be prevented, targeted preventive measures should be taken according to the characteristics of children′s accidental injuries in different regions, and a comprehensive prevention system for children′s accidental injuries should be constructed to ensure children′s safety.
8.Risk Factors for Gestational Diabetes Mellitus (GDM) in Subsequent Pregnancy Among Women Without GDM History in China: A Multicenter Retrospective Study
Geng SONG ; Yumei WEI ; Juan JUAN ; Rina SU ; Jianying YAN ; Mei XIAO ; Xianlan ZHAO ; Meihua ZHANG ; Yuyan MA ; Haiwei LIU ; Jingxia SUN ; Kejia HU ; Huixia YANG
Maternal-Fetal Medicine 2023;05(1):9-15
Objective::This study aimed to determine the likelihood of gestational diabetes mellitus (GDM) in subsequent pregnancy among women without GDM history and to identify risk factors for GDM in subsequent pregnancy.Methods::This retrospective cohort study involved participants who delivered twice in same hospital of 18 research centers when delivered the second baby from January 2018 to December 2018. Finally 6204 women were enrolled and 5180 women without GDM history were analyzed further. Women were categorized as non-GDM or GDM based on the blood glucose values of the subsequent pregnancy, and the characteristics and GDM risk of these groups were compared. A univariate analysis of potential risk factors was performed using the Chi-squared test and/or t-test for qualitative or quantitative variables, respectively. Associations with P values <0.1 were chosen to be included in the multivariate binary logistic regression model. Results::In primary analysis of 6204 women, the incidence of GDM in subsequent pregnancy is 48.9% (490/1002) in women with GDM history and 16.1% (835/5202) in women without GDM history. In a further analysis for 5180 women without GDM at index pregnancy, compared with the non-GDM group, the GDM group had a significantly higher age, prepregnancy body mass index, and blood glucose value at each oral glucose tolerance test (OGTT) timepoint (fasting, 1 h and 2 h) during the index and subsequent pregnancies, as well as higher weight retention during the interval between the two pregnancies ( P<0.001). Age above 35 years in subsequent pregnancy (odds ratio ( OR)=1.540, 95% confidence interval ( CI) = 1.257-1.886, P<0.001), macrosomia in index pregnancy ( OR=1.749, 95% CI=1.277-2.395, P=0.001), OGTT blood glucose values in index pregnancy (fasting, OR=2.487, 95% CI=1.883-3.285, P<0.001; 1 h, OR=1.142, 95% CI=1.051-1.241, P=0.002; 2 h, OR=1.290, 95% CI=1.162-1.432, P<0.001) and weight retention ( OR=1.052, 95% CI=1.035-1.068, P<0.001) were independent risk factors for GDM in subsequent pregnancy. Conclusion::For women without GDM history, GDM risk factors including age, macrosomia history, OGTT value, and weight retention, these can be evaluated before a subsequent pregnancy. Early warning and interventions are needed for women at high risk.
9.Risk Factors for Gestational Diabetes Mellitus (GDM) in Subsequent Pregnancy Among Women Without GDM History in China: A Multicenter Retrospective Study
Geng SONG ; Yumei WEI ; Juan JUAN ; Rina SU ; Jianying YAN ; Mei XIAO ; Xianlan ZHAO ; Meihua ZHANG ; Yuyan MA ; Haiwei LIU ; Jingxia SUN ; Kejia HU ; Huixia YANG
Maternal-Fetal Medicine 2023;05(1):9-15
Objective::This study aimed to determine the likelihood of gestational diabetes mellitus (GDM) in subsequent pregnancy among women without GDM history and to identify risk factors for GDM in subsequent pregnancy.Methods::This retrospective cohort study involved participants who delivered twice in same hospital of 18 research centers when delivered the second baby from January 2018 to December 2018. Finally 6204 women were enrolled and 5180 women without GDM history were analyzed further. Women were categorized as non-GDM or GDM based on the blood glucose values of the subsequent pregnancy, and the characteristics and GDM risk of these groups were compared. A univariate analysis of potential risk factors was performed using the Chi-squared test and/or t-test for qualitative or quantitative variables, respectively. Associations with P values <0.1 were chosen to be included in the multivariate binary logistic regression model. Results::In primary analysis of 6204 women, the incidence of GDM in subsequent pregnancy is 48.9% (490/1002) in women with GDM history and 16.1% (835/5202) in women without GDM history. In a further analysis for 5180 women without GDM at index pregnancy, compared with the non-GDM group, the GDM group had a significantly higher age, prepregnancy body mass index, and blood glucose value at each oral glucose tolerance test (OGTT) timepoint (fasting, 1 h and 2 h) during the index and subsequent pregnancies, as well as higher weight retention during the interval between the two pregnancies ( P<0.001). Age above 35 years in subsequent pregnancy (odds ratio ( OR)=1.540, 95% confidence interval ( CI) = 1.257-1.886, P<0.001), macrosomia in index pregnancy ( OR=1.749, 95% CI=1.277-2.395, P=0.001), OGTT blood glucose values in index pregnancy (fasting, OR=2.487, 95% CI=1.883-3.285, P<0.001; 1 h, OR=1.142, 95% CI=1.051-1.241, P=0.002; 2 h, OR=1.290, 95% CI=1.162-1.432, P<0.001) and weight retention ( OR=1.052, 95% CI=1.035-1.068, P<0.001) were independent risk factors for GDM in subsequent pregnancy. Conclusion::For women without GDM history, GDM risk factors including age, macrosomia history, OGTT value, and weight retention, these can be evaluated before a subsequent pregnancy. Early warning and interventions are needed for women at high risk.
10.Automatic synthesis and in vivo imaging of Al 18F-NOTA-FAPI-04
Xiao JIANG ; Xiaoxiong WANG ; Taipeng SHEN ; Yutang YAO ; Xiuli LI ; Jiaqi SHEN ; Ying KOU ; Meihua CHEN ; Shirong CHEN ; Dingqiong XIAO ; Meng ZHAO ; Hao LU ; Jiayu LI ; Shengyan HU ; Xiaoping HU ; Zhifu LUO ; Xing ZHOU ; Chuan LI ; Zhuzhong CHENG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2022;42(1):31-35
Objective:To automatically synthesize Al 18F-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-fibroblast activation protein inhibitor (FAPI)-04, perform PET/CT imaging in vivo, and evaluate its diagnostic efficacy on tumors. Methods:Al 18F-NOTA-FAPI-04 was produced in All-in-one automatic synthesis module and its quality control was conducted by high performance liquid chromatography (HPLC) equipped with a radioactive detector. Al 18F-NOTA-FAPI-04 PET/CT imaging was performed in normal BALB/c mice ( n=3) and 4T1 breast cancer models ( n=3) to determine its biodistribution. Then Al 18F-NOTA-FAPI-04 and 18F-FDG PET/CT imaging were performed in a hepatocellular carcinoma patient (male, 51 years old). Results:The synthesis time of Al 18F-NOTA-FAPI-04 was about 35 min, and the radiochemical yield was (25.2±1.9)% (attenuation correction, n=3). The product was colorless transparent solution with pH value of 7.0-7.5, and the specific activity was (46.11±3.07) GBq/μmol (attenuation correction, n=3). The radiochemical purity was above 99.0% and was still above 98.0% at room temperature after 6 h. PET/CT imaging in mice showed that physiological uptake of Al 18F-NOTA-FAPI-04 was mainly in biliary system and bladder, and Al 18F-NOTA-FAPI-04 highly concentrated in tumor xenografts. PET/CT imaging in the patient showed that Al 18F-NOTA-FAPI-04 obtained high tumor background ratio (TBR) values of 4.1, 8.9, 5.4, 4.8, 2.2 in parasternal lymph nodes, anterior diaphragmatic lymph nodes, hilar lymph nodes, pancreaticoduodenal ligament lymph nodes, abdominal aortic lymph nodes, respectively, while TBR values were 1.0, 2.8, 5.0, 2.1, 1.1 by 18F-FDG. Conclusions:Al 18F-NOTA-FAPI-04 can be synthesized with short time, high radiochemical yield and good stability using All-in-one module. Al 18F-NOTA-FAPI-04 PET/CT imaging has high contrast and excellent diagnostic efficacy on tumors.


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