1.Compound Glycyrrhizin Tablets Ameliorate Liver Injury Induced by Tripterygium Glycosides Tablet by Regulating Cholesterol Metabolism
Xiaotong FU ; Chunyu CAO ; Chun LI ; Chenna LU ; Ting LIU ; Yifei YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):46-55
ObjectiveTo investigate the mechanism of liver injury induced by tripterygium glycosides tablets (TG) and the molecular mechanism of compound glycyrrhizin tablets (CG) in alleviating the abnormalities of cholesterol metabolism caused by TG via cholesterol metabolism. MethodsAccording to the body weights, male Sprague-Dawley (SD) rats were randomly grouped as follows: control (pure water), low-dose TG (TG-L, 189.0 mg·kg-1·d-1), high-dose TG (TG-H, 472.5 mg·kg-1·d-1), TG-L+CG (189.0 mg·kg-1·d-1 TG + 20.25 mg·kg-1·d-1 CG), and TG-H+CG (472.5 mg·kg-1·d-1 TG + 20.25 mg·kg-1·d-1 CG), with 6 rats in each group. Rats were administrated with corresponding drugs once daily for 3 weeks. At the end of the last administration, the mRNA and protein levels of liver X receptor-alpha (LXR-α), low-density lipoprotein receptor (LDLR), adenosine triphosphate-binding cassette transporter A1 (ABCA1), adenosine triphosphate-binding cassette transporter G1 (ABCG1), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), cholesterol 12α-hydroxylase (CYP8B1), and sterol 27-hydroxylase (CYP27A1) in the liver tissue were determined by Real-time PCR and Western blotting, respectively. The level of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR), a regulatory enzyme of cholesterol synthesis, was measured by enzyme-linked immunosorbent assay (ELISA). HepG2 cells were used to observe the effect of TG on the cell proliferation in vitro. Specifically, HepG2 cells were grouped as follows: Low-dose TG (TG-l, 15 mg·L-1), medium-dose TG (TG-m, 45 mg·L-1), high-dose TG (TG-h, 135 mg·L-1), fenofibrate (FB, 10 μmol·L-1), CG extract, TG-h+FB (135 mg·L-1 TG + 10 μmol·L-1 FB), TG-m+FB (45 mg·L-1 TG + 10 μmol·L-1 FB), TG-l+FB (15 mg·L-1 TG + 10 μmol·L-1 FB), TG-h+CG (135 mg·L-1 TG + 60 μmol·L-1 CG), TG-m+CG (45 mg·L-1 TG + 60 μmol·L-1 CG), and TG-l+CG (15 mg·L-1 TG + 60 μmol·L-1 CG). The mRNA and protein levels of LXR-α, ABCG1, LDLR, CYP7A1, CYP8B1, and CYP27A1 in HepG2 cells were determined by Real-time PCR and Western blotting, respectively. ResultsThe rat experiment showed that compared with the control group, the TG-H group showed down-regulated mRNA levels of CYP7A1, CYP8B1, and CYP27A1 in the liver tissue (P<0.05, P<0.01), which were up-regulated by the application of CG (P<0.05, P<0.01), and the TG-H+CG group showed up-regulated mRNA level of LDLR (P<0.01). Compared with the control group, the TG-L and TG-H groups showed down-regulated protein levels of LDLR, CYP7A1, and CYP8B1 in the liver tissue (P<0.05, P<0.01). In addition, the protein levels of ABCG1 and LXR-α were down-regulated in the TG-H and TG-L groups, respectively (P<0.05). Compared with TG alone, TG+CG up-regulated the protein levels of ABCG1 and LDLR (P<0.05, P<0.01), and the protein levels of CYP7A1 and CYP8B1 in the TG-H+CG group were up-regulated (P<0.05, P<0.01). The cell experiment showed that compared with the control group, the TG-h group presented up-regulated mRNA level of LXR-α (P<0.01), and the TG-m and TG-h groups showcased down-regulated mRNA levels of LDLR and CYP7A1 (P<0.01) and up-regulated mRNA level of CYP27A1 (P<0.01) in HepG2 cells. The combination of CG with TG restored the above changes (P<0.01). Western blotting results showed that compared with the control group, the TG-m and TG-h groups showed down-regulated protein levels of LXR-α, ABCG1, LDLR, CYP7A1, CYP8B1, and CYP27A1 in HepG2 cells (P<0.01). Compared with the TG-h group, the TG-h+CG group showed up-regulated protein level of LDLR (P<0.05). Compared with the TG-m group, the TG-m+CG group showcased up-regulated protein levels of LDLR, ABCG1, CYP7A1, and CYP27A1 (P<0.05, P<0.01). ConclusionThe administration of TG at 189.0, 472.5 mg·kg-1 for 3 weeks could modulate the signaling pathways associated with cholesterol efflux, endocytosis, and cholesterol biotransformation in hepatocytes, leading to the accumulation of cholesterol and subsequent liver injury in rats. CG could ameliorate the liver injury induced by lipid metabolism disorders caused by TG by up-regulating the expression of LXR-α, LDLR, ABCG1, CYP7A1, CYP8B1, and CYP27A1 to promote cholesterol biotransformation.
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.Comparison of Mg-Li-Gd alloy and stainless steel intramedullary nail for fixation of femoral annular hemi-defects in rats
Jingshuai WANG ; Xiaotong ZHANG ; Yange ZHANG ; Zedong WAN ; Lingwei KONG ; Haiying CAO ; Yu JIN
Chinese Journal of Tissue Engineering Research 2025;29(34):7261-7268
BACKGROUND:With the increasing demand for orthopedic implants,the search for materials with good biocompatibility and degradability has become a research hotspot.Magnesium-lithium-gadolinium(Mg-Li-Gd)alloy has good degradability,biocompatibility,and mechanical properties,providing ideal supporting conditions for fracture healing.OBJECTIVE:To evaluate the effects of Mg-Li-Gd alloy implants on bone healing in rats.METHODS:A circular half-defect model was made on the lateral side of the right mid-femoral segment in 28 SD rats,and the rats were randomly divided into two groups.The stainless steel group was fixed with a stainless steel intramedullary nail,and the magnesium alloy group was fixed with an Mg-Li-Gd alloy intramedullary nail,with 14 rats in each group.At 2,8,and 14 weeks after surgery,right femur X-ray and Micro-CT examinations,as well as hematoxylin-eosin staining,immunohistochemical staining,and western blot assay were performed.RESULTS AND CONCLUSION:(1)X-ray film:At 2 weeks after surgery,the osteotomy lines of both groups were clear,the density of the intramedullary nail in the magnesium alloy group was close to that of bone tissue,and the density of the intramedullary nail in the stainless steel group was higher than that of bone tissue.At 8 weeks after surgery,the osteotomy lines of both groups were blurred,and the intramedullary nail in the magnesium alloy group had corroded and degraded.At 14 weeks after surgery,the osteotomy lines of both groups disappeared,and the intramedullary nail in the magnesium alloy group further corroded and degraded.(2)Micro-CT:At 2 weeks after surgery,callus began to form in both groups;8 weeks after surgery,the stainless steel group entered the callus remodeling stage,and a relatively dense bone structure was formed at the bone defect site,and the magnesium alloy group showed obvious callus hyperplasia at the bone defect site.At 14 weeks after surgery,the stainless steel group showed a mature bone remodeling process,and thick cortical bone was formed at the bone defect site,and thinner cortical bone was formed in the magnesium alloy group.(3)Hematoxylin-eosin staining:At 2 weeks after surgery,a large number of osteoblasts,osteocytes,a small number of osteoclasts and trabecular structures were observed in the magnesium alloy group,while relatively few osteoblasts and osteocytes were observed in the stainless steel group.At 8 weeks after surgery,a large number of osteoblasts,osteocytes,and mature trabecular structures were observed in the magnesium alloy group,while a large number of osteocytes and lamellar bones were observed in the stainless steel group.At 14 weeks after surgery,lamellar bones were observed in the magnesium alloy group,while mature bone tissue was observed in the stainless steel group.(4)Immunohistochemical staining and western blot assay:At the same time point,the expression levels of bone morphogenetic protein 2,osteocalcin,and RUNX2 proteins in the magnesium alloy group were higher than those in the stainless steel group.(5)The results showed that compared with stainless steel materials,Mg-Li-Gd alloy had no obvious advantage in promoting the formation of fracture healing structure.
4.Comparison of Mg-Li-Gd alloy and stainless steel intramedullary nail for fixation of femoral annular hemi-defects in rats
Jingshuai WANG ; Xiaotong ZHANG ; Yange ZHANG ; Zedong WAN ; Lingwei KONG ; Haiying CAO ; Yu JIN
Chinese Journal of Tissue Engineering Research 2025;29(34):7261-7268
BACKGROUND:With the increasing demand for orthopedic implants,the search for materials with good biocompatibility and degradability has become a research hotspot.Magnesium-lithium-gadolinium(Mg-Li-Gd)alloy has good degradability,biocompatibility,and mechanical properties,providing ideal supporting conditions for fracture healing.OBJECTIVE:To evaluate the effects of Mg-Li-Gd alloy implants on bone healing in rats.METHODS:A circular half-defect model was made on the lateral side of the right mid-femoral segment in 28 SD rats,and the rats were randomly divided into two groups.The stainless steel group was fixed with a stainless steel intramedullary nail,and the magnesium alloy group was fixed with an Mg-Li-Gd alloy intramedullary nail,with 14 rats in each group.At 2,8,and 14 weeks after surgery,right femur X-ray and Micro-CT examinations,as well as hematoxylin-eosin staining,immunohistochemical staining,and western blot assay were performed.RESULTS AND CONCLUSION:(1)X-ray film:At 2 weeks after surgery,the osteotomy lines of both groups were clear,the density of the intramedullary nail in the magnesium alloy group was close to that of bone tissue,and the density of the intramedullary nail in the stainless steel group was higher than that of bone tissue.At 8 weeks after surgery,the osteotomy lines of both groups were blurred,and the intramedullary nail in the magnesium alloy group had corroded and degraded.At 14 weeks after surgery,the osteotomy lines of both groups disappeared,and the intramedullary nail in the magnesium alloy group further corroded and degraded.(2)Micro-CT:At 2 weeks after surgery,callus began to form in both groups;8 weeks after surgery,the stainless steel group entered the callus remodeling stage,and a relatively dense bone structure was formed at the bone defect site,and the magnesium alloy group showed obvious callus hyperplasia at the bone defect site.At 14 weeks after surgery,the stainless steel group showed a mature bone remodeling process,and thick cortical bone was formed at the bone defect site,and thinner cortical bone was formed in the magnesium alloy group.(3)Hematoxylin-eosin staining:At 2 weeks after surgery,a large number of osteoblasts,osteocytes,a small number of osteoclasts and trabecular structures were observed in the magnesium alloy group,while relatively few osteoblasts and osteocytes were observed in the stainless steel group.At 8 weeks after surgery,a large number of osteoblasts,osteocytes,and mature trabecular structures were observed in the magnesium alloy group,while a large number of osteocytes and lamellar bones were observed in the stainless steel group.At 14 weeks after surgery,lamellar bones were observed in the magnesium alloy group,while mature bone tissue was observed in the stainless steel group.(4)Immunohistochemical staining and western blot assay:At the same time point,the expression levels of bone morphogenetic protein 2,osteocalcin,and RUNX2 proteins in the magnesium alloy group were higher than those in the stainless steel group.(5)The results showed that compared with stainless steel materials,Mg-Li-Gd alloy had no obvious advantage in promoting the formation of fracture healing structure.
5.NAT10 inhibition alleviates astrocyte autophagy by impeding ac4C acetylation of Timp1 mRNA in ischemic stroke.
Li YANG ; Xiaotong LI ; Yaxuan ZHAO ; Hao CHEN ; Can WANG ; Angrong WU ; Xintong GUO ; Yue HUANG ; Qihui WANG ; Lingyun HAO ; Xiaowen LI ; Ying JI ; Jin BAN ; Guangtian WANG ; Junli CAO ; Zhiqiang PAN
Acta Pharmaceutica Sinica B 2025;15(5):2575-2592
Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.
6.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.
7.Analysis of pollution status and influencing factors of polybrominated diphenyl ethers in household dust in five cities in northern China
Xiaotong ZHANG ; Yun CAO ; Wenying ZHANG ; Linlin JIANG ; Mengmeng LIU ; Fengjing SONG ; Tingting LIU ; Chengyu CHEN ; Li LI ; Hang LIU ; Lin FAN ; Hang DU ; Yiming SUN ; Chao WANG ; Bin LUO ; Xianliang WANG
Chinese Journal of Preventive Medicine 2024;58(10):1514-1523
Objective:To investigate the pollution levels and influencing factors of polybrominated diphenyl ethers (PBDEs) in household dust in five cities in northern China.Methods:Based on the "Chinese Indoor Environment and Health Surveillance" project carried out by the National Institute of Environmental Health, Chinese Center for Disease Control and Prevention in 2018-2019, during the warm season (April 2018 to September 2018) and the cold season (November 2018 to March 2019), Lanzhou in Northwest China, Shijiazhuang in North China, Panjin in Northeast China, Luoyang in Central China, and Qingdao in East China were selected as the research sites. A total of 87 families were recruited to study residences in real-life scenarios. At the same time, dust samples were collected to detect the concentration of PBDEs. The level of household environmental indicators was measured, and the residential building characteristics and family behavior habits were collected through questionnaires. A total of 142 valid dust samples and 140 valid questionnaires were obtained. The differences in PBDE concentrations across seasons, wind zones, residential building characteristics, and family habits were analyzed. The exploratory factor analysis was performed to investigate the possible sources of PBDEs, and multivariate linear regression was used to explore the factors influencing PBDEs in household dust.Results:The M ( Q1,Q3) of total PBDE concentrations in 142 household dust samples in five cities was 144.51 (106.61, 222.65) ng/g in the warm season and 145.10 (98.57, 180.65) ng/g in the cold season, respectively. There were seasonal differences in the concentration of ∑ 12PBDEs in Luoyang and Shijiazhuang ( P<0.01). The concentration of BDE-71 was highest among PBDE homologues, followed by BDE-66 and BDE-47. Three factors were extracted by exploratory factor analysis in the warm season, and the cumulative variance contribution rate was 67.90%. The multivariate linear regression showed that the house completion less than ten years [ β (95% CI): 0.186 (0.013, 0.359)], infrequent home cooking [ β (95% CI):-0.342 (-0.570, -0.114)], and increased residential PM 10 concentration [ β (95% CI): 0.001 (0.000, 0.002)] during the warm season, as well as the house far from driveway [ β (95% CI): 0.093 (0.013, 0.172)], house area less than 90 m 2 [ β (95% CI):-0.138 (-0.264, -0.013)], and lower residential xylene concentration [ β (95% CI):-0.006 (-0.011, -0.001)] during the cold season might be related to the elevated concentrations of ∑ 12PBDEs in household dust. Conclusion:The pollution of PBDEs in household dust in five northern cities is at a medium to high level. Years of house completion, frequency of cooking at home, residential PM 10 concentration, distance from house to driveway, house area, and residential xylene concentration may influence household PBDE concentrations.
8.Research Progress on Ferroptosis,Ulcerative Colitis and Treatment with Traditional Chinese Medicine
Xiaotong LI ; Jiali LI ; Zhiqun CAO ; Nan KANG ; Weizhi KONG ; Zhidong YOU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(4):861-867
Ulcerative colitis is a chronic,non-specific inflammatory disease.The persistent damage to its intestinal epithelium is key to the development of the disease.In recent years,a new form of cell death has been identified by researchers-iron death-which is thought to be an important contributor to intestinal epithelial cell death.The occurrence of iron death is often associated with abnormal intracellular iron metabolism,reduced cystine/glutamate reverse transporter activity,abnormal lipid metabolism,voltage-dependent anion channel activation and overexpression of the Nrf2 gene.Iron death can lead to smaller mitochondria,increased membrane density and reduced number of cristae,unlike conventional cell death,which does not exhibit specific phenomena.Studies have found that TCM can alleviate iron death in intestinal epithelial cells by reducing intracellular iron content,inhibiting lipid reactive oxygen species production and regulating Nrf2 gene expression,thus acting as a treatment for ulcerative colitis.Therefore,Chinese medicine may become an important tool for the treatment of ulcerative colitis.This paper reviews the relationship between cellular iron death and ulcerative colitis and the research progress of Chinese medicine in treating ulcerative colitis through the iron death pathway.
9.Analysis of pollution status and influencing factors of polybrominated diphenyl ethers in household dust in five cities in northern China
Xiaotong ZHANG ; Yun CAO ; Wenying ZHANG ; Linlin JIANG ; Mengmeng LIU ; Fengjing SONG ; Tingting LIU ; Chengyu CHEN ; Li LI ; Hang LIU ; Lin FAN ; Hang DU ; Yiming SUN ; Chao WANG ; Bin LUO ; Xianliang WANG
Chinese Journal of Preventive Medicine 2024;58(10):1514-1523
Objective:To investigate the pollution levels and influencing factors of polybrominated diphenyl ethers (PBDEs) in household dust in five cities in northern China.Methods:Based on the "Chinese Indoor Environment and Health Surveillance" project carried out by the National Institute of Environmental Health, Chinese Center for Disease Control and Prevention in 2018-2019, during the warm season (April 2018 to September 2018) and the cold season (November 2018 to March 2019), Lanzhou in Northwest China, Shijiazhuang in North China, Panjin in Northeast China, Luoyang in Central China, and Qingdao in East China were selected as the research sites. A total of 87 families were recruited to study residences in real-life scenarios. At the same time, dust samples were collected to detect the concentration of PBDEs. The level of household environmental indicators was measured, and the residential building characteristics and family behavior habits were collected through questionnaires. A total of 142 valid dust samples and 140 valid questionnaires were obtained. The differences in PBDE concentrations across seasons, wind zones, residential building characteristics, and family habits were analyzed. The exploratory factor analysis was performed to investigate the possible sources of PBDEs, and multivariate linear regression was used to explore the factors influencing PBDEs in household dust.Results:The M ( Q1,Q3) of total PBDE concentrations in 142 household dust samples in five cities was 144.51 (106.61, 222.65) ng/g in the warm season and 145.10 (98.57, 180.65) ng/g in the cold season, respectively. There were seasonal differences in the concentration of ∑ 12PBDEs in Luoyang and Shijiazhuang ( P<0.01). The concentration of BDE-71 was highest among PBDE homologues, followed by BDE-66 and BDE-47. Three factors were extracted by exploratory factor analysis in the warm season, and the cumulative variance contribution rate was 67.90%. The multivariate linear regression showed that the house completion less than ten years [ β (95% CI): 0.186 (0.013, 0.359)], infrequent home cooking [ β (95% CI):-0.342 (-0.570, -0.114)], and increased residential PM 10 concentration [ β (95% CI): 0.001 (0.000, 0.002)] during the warm season, as well as the house far from driveway [ β (95% CI): 0.093 (0.013, 0.172)], house area less than 90 m 2 [ β (95% CI):-0.138 (-0.264, -0.013)], and lower residential xylene concentration [ β (95% CI):-0.006 (-0.011, -0.001)] during the cold season might be related to the elevated concentrations of ∑ 12PBDEs in household dust. Conclusion:The pollution of PBDEs in household dust in five northern cities is at a medium to high level. Years of house completion, frequency of cooking at home, residential PM 10 concentration, distance from house to driveway, house area, and residential xylene concentration may influence household PBDE concentrations.
10.Epidemiological characteristics and pathogenic analysis of hand,foot,and mouth disease in Hebei province
Zehao LIU ; Le WANG ; Yanyan CAO ; Xiaotong YAN ; Xin ZHAO ; Wenhui LI ; Shengwang GE
Basic & Clinical Medicine 2024;44(9):1279-1283
Objective To identify epidemiological characteristics and pathogen distribution of hand,foot,and mouth disease(HFMD)in Hebei Children's Hospital in order to support prevention and treatment of HFMD.Methods A total of 1 698 cases throat swab samples from children diagnosed as HFMD from 2016 to 2023 were collected.Real-time PCR was used to detect the specific classification of HFMD.Statistical analysis was performed according to the year,season,age,and sex and enterovirus type of HFMD in the children.Results From 2016 to 2023,the ratio of male to female patients among the 1 698 children admitted to Hebei Children's Hospital was 1.72∶1.Among them,the highest incidence rate in summer was 778 cases,accounting for 45.8%of all cases,followed by autumn,with a total of 614 cases,accounting for 36.2%of cases.The highest incidence was recorded in age group of 1-3 years,with a total of 1 032 cases(60.8%).The lowest incidence was 38 cases in age group>6 years old(2.2%);There were 988 cases of HFM(58.2%)caused by different strains of enterovirus undefined(EVU)except enterovirus 71(EV71)and coxsackievirus A16(CA16).Conclusions HFMD found in Hebei Children's Hospital from 2016 to 2023 are mainly caused by enteroviruses except EV 71 and coxsackievirus A16.High morbid-ity is found in children aged 1-3 years,and summer and autumn are the main epidemic seasons.This result may facilitate and support decision making and strategy development in disease prevention and control as well as to strengthen public health resources.

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