1.Combination of Components from Tripterygii Radix et Rhizoma-Chuanxiong Rhizoma Affects RA-FLSs by Regulating NF-κB, Nrf2/HO-1 Signaling Pathways and Bcl-2/Caspase-3 Expression
Yongmei GUAN ; Zhiyan WAN ; Shuhui WANG ; Weifeng ZHU ; Zhiyong LIU ; Cheng JIANG ; Zhenzhong ZANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):17-26
ObjectiveTo investigate the effects of the combination of components from Tripterygii Radix et Rhizoma and Chuanxiong Rhizoma on rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) and the underlying mechanism. MethodsRA-FLSs were grouped as follows: blank control, positive control (methotrexate), Tripterygii Radix et Rhizoma components, Chuanxiong Rhizoma components, and components from Tripterygii Radix et Rhizoma+Chuanxiong Rhizoma. The cell-counting kit-8 (CCK-8) assay was employed to the cell proliferation, invasion, and apoptosis. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, reactive oxygen species (ROS), and malondiadehyde (MDA) in cells were measured. Western blot was employed to determine the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), nuclear factor-kappa B (NF-κB) p65, phosphorylated inhibitory subunit of NF-κBα (p-IκBα), cysteinyl aspartate-specific protease-3 (Caspase-3), and B-cell lymphoma 2 (Bcl-2). Real-time PCR was employed to determine the mRNA levels of Nrf2, HO-1, and NF-κB p65. ResultsThe cells in the groups of positive control, Tripterygii Radix et Rhizoma components, Chuanxiong Rhizoma components, and components from Tripterygii Radix et Rhizoma+Chuanxiong Rhizoma were treated with 2.50 mg·L-1 methotrexate, 0.20 mg·L-1 triptolide + 0.20 mg·L-1 celastrol, 5.00 mg·L-1 ferulic acid + 20.00 mg·L-1 ligustrazine, 0.20 mg·L-1 triptolide + 0.20 mg·L-1 celastrol + 5.00 mg·L-1 ferulic acid + 20.00 mg·L-1 ligustrazine, respectively. Compared with the blank control group, drug administration reduced the proliferation and invasion and increased the apoptosis of cells (P<0.01), lowered the levels of TNF-α, IL-6, ROS, and MDA (P<0.01), up-regulated the mRNA and protein levels of Caspase-3, Nrf2, and HO-1 (P<0.01), and down-regulated the mRNA and protein levels of Bcl-2, NF-κB p65, and p-IκBα (P<0.01). Compared with the Tripterygii Radix et Rhizoma components group, the combination of components from Tripterygii Radix et Rhizoma+Chuanxiong Rhizoma inhibited the proliferation and invasion (P<0.05) and promoted the apoptosis of RA-FLSs, up-regulated the mRNA levels of Nrf2 and HO-1 and protein levels of Nrf2 and Caspase-3 (P<0.05), and down-regulated the protein levels of NF-κB p65 and p-IκBα (P<0.05). ConclusionThe combination of components from Chuanxiong Rhizoma and Tripterygii Radix et Rhizoma can inhibit the proliferation and invasion and promote the apoptosis of RA-FLSs and alleviate oxidative stress and inflammation by inhibiting the NF-κB signaling pathway, activating the Nrf2/HO-1 pathway, and regulating the expression of Bcl-2/Caspase-3.
2.Application of scaffolding-based flipped classroom in Infectious Disease Nursing
Fei ZHAO ; Zhiyan BAO ; Rong CHEN ; Leyao XIAO ; Fenlian ZENG ; Xia LIU ; Chunmei YAO ; Kangyan LIU ; Shuozhen CHEN ; Song LI ; Ping YANG
Chinese Journal of Medical Education Research 2024;23(3):401-405
Objective:To explore the effects of the scaffolding-based flipped classroom approach in the teaching of Infectious Disease Nursing. Methods:We assigned 152 students of nursing and midwifery majors of grade 2018 (experimental group) to be taught using the scaffolding-based flipped classroom approach and 182 students of grade 2017 (control group) to be taught using the traditional lecture method. Teaching effects were evaluated through students' exam performance and a questionnaire survey. Numerical data were analyzed using the χ2 test and t test with the use of SPSS 18.0, and text data were processed using NVivo 11 for thematic analysis. Results:The experimental group and control group showed significant differences in the interim exam score (83.19±7.96 vs. 79.62±3.14, P<0.001) and final exam score (78.47±6.92 vs. 73.16±8.24, P<0.001). The students of grade 2018 had a high level of participation in online learning. The questionnaire results showed that the scaffolding-based flipped classroom was well recognized in terms of students' overall perception, perceived course quality, perceived value of learning, and satisfaction and the open-ended question, with low scores for learner complaints and loyalty. Conclusions:The scaffolding-based flipped classroom is feasible in the teaching of Infectious Disease Nursing, which can improve students' academic performance and overall competence.
3.Interpretation of the 5th edition WHO classification of adrenal cortical tumors
Chinese Journal of Pathology 2024;53(1):16-21
Non-neoplastic lesions were added in the 5th edition WHO classification of adrenal cortical tumor based on the recent update, including adrenal rests, adrenal cysts, congenital adrenal hyperplasia and adrenocortical nodular disease. A range of tumor concepts were updated or refined based on tumor cell origin, histopathology, oncology and molecular biology. The most significant nomenclature change in the field of adrenal cortical pathology involves the refined classification of adrenal cortical nodular disease, which now includes sporadic nodular adrenocortical disease, bilateral micronodular adrenal cortical disease, and bilateral macronodular adrenal cortical disease. The 5th edition WHO classification endorses the nomenclature of the HISTALDO classification to help the classification of aldosterone producing adrenal cortical lesions, which uses CYP11B2 immunohistochemistry to identify functional sites of aldosterone production. The 5th edition WHO classification does not change the Weiss and Lin-Weiss-Bisceglia histopathologic criteria for diagnosing adrenal cortical carcinomas, and underscores the diagnostic and prognostic impact of angioinvasion in these tumors. Reticulin algorithm and Helsinki scoring system were added to assist the differential diagnosis of adrenal cortical neoplasms in adults. Pediatric adrenal cortical neoplasms are assessed using the Wieneke system. The 5th edition WHO classification places an emphasis on an accurate assessment of tumor proliferation rate using both the mitotic count (mitoses per 10 mm 2) and Ki-67 labeling index which play an essential role in the dynamic risk stratification of affected patients. This review highlights advances in knowledge of histological features, ancillary studies, and associated genetic findings that increase the understanding of the adrenal cortex pathologies in the 5th edition WHO classification.
4.Analysis of prognostic factors for clear cell adenocarcinoma of the uterine cervix based on the Surveillance, Epidemiology and End Results database
Zhiyan LIU ; Ruifeng XUE ; Yang WANG ; Jianhao GENG ; Rongxu DU ; Yongheng LI ; Weihu WANG
Cancer Research and Clinic 2024;36(3):161-166
Objective:To explore the prognostic factors associated with clear cell adenocarcinoma (CCAC) of the uterine cervix based on data in the Surveillance, Epidemiology and End Results (SEER) database.Methods:Clinical data were collected from 431 patients with confirmed CCAC in the SEER database from 1976 to 2017. Survival analysis was performed using the Kaplan-Meier method with log-rank test for comparison between subgroups. Cox proportional hazards model was used to analyze the influencing factors of overall survival (OS).Results:The median age [ M ( Q1, Q3)] of 431 patients was 54 years old (40 years old, 71 years old); there were 333 cases (77.3%) of whit. The median OS time of 431 patients was 93 months (95% CI: 47-148 months), and the 1-, 2-, and 5-year OS rates were 80.1%, 65.8% and 54.2%, respectively. The median OS time was not reached in patients with American Joint Committee on Cancer (AJCC) stage Ⅰ, 83 months (95% CI: 21-144 months) for stage Ⅱ, 32 months (95% CI: 16-47 months) for stage Ⅲ, and 9 months (95% CI: 5-13 months) for stage Ⅳ ( P < 0.001). Median OS time was not reached in patients with SEER stage of localized lesions, 46 months (95% CI: 8-83 months) for regional lesions stage, and 9 months (95% CI: 5-12 months) for distant metastases stage ( P < 0.001). Of the patients with clear AJCC staging and some with unspecified AJCC staging, 118 received surgical treatment alone and 119 received postoperative radiotherapy, the median OS time of the two groups was 443 months (95% CI: 162-723 months) and 102 months (95% CI: 75-129 months), and the difference in OS between the two groups was statistically significant ( P < 0.001). Among the patients with AJCC stage Ⅰ, the 5-year OS rates in surgery-only group and postoperative radiotherapy group were 82.5% and 78.5%, the stage Ⅱ were 80.0% and 52.3%, and the stage Ⅲ were 27.8% and 63.3%, respectively; the differences in OS between different stages were not statistically significant (all P>0.05). Among the patients with SEER localized lesions stage, the 5-year OS rates in surgery-only group and postoperative radiotherapy group were 88.9% and 73.1%, and the difference was statistically significant ( P = 0.012); the regional lesions stage were 45.5% and 60.0%, and the difference was not statistically significant ( P = 0.568). The results of multivariate Cox regression analysis showed that AJCC staging (stage Ⅰ vs. stage Ⅳ, HR = 0.281, 95% CI: 0.178-0.543, P < 0.001; stage Ⅱ vs. stage Ⅳ, HR = 0.347, 95% CI: 0.113-0.439, P < 0.001; stage Ⅲ vs. stage Ⅳ, HR = 0.399, 95% CI: 0.030-0.145, P < 0.001), SEER staging (localized lesions stage vs. distant metastases stage, HR = 0.104, 95% CI: 0.059-0.182, P < 0.001; regional lesions stage vs. distant metastases stage, HR = 0.301, 95% CI: 0.195-0.463, P < 0.001) and whether or not receive surgery (yes vs. no, HR = 0.359, 95% CI: 0.241-0.535, P < 0.001) were independent influencing factors of OS in CCAC patients. Conclusions:AJCC staging, SEER staging and surgery are independent influence factors for OS in patients with CCAC, and postoperative radiotherapy may not provide more survival benefit.
5.Yunpi Huatan Tongqiao Prescription Regulates Microglial Cell Polarization Phenotype to Improve Inflammation and Cognitive Impairment in OSA Mice by Down-regulating Glycolysis
Wenyan PU ; Anqi LIU ; Yan LIN ; Xuejun LI ; Hongyu ZHANG ; Zhiyan JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):35-42
ObjectiveTo validate the efficacy of Yunpi Huatan Tongqiao prescription (YHTP) in down-regulating glycolysis to modulate microglia phenotype and improve inflammation and cognitive memory deficits in obstructive sleep apnea (OSA) mice. MethodForty-eight male Balb/C mice were randomly divided into a normal group, a model group, a montelukast sodium group (30 mg·kg-1), and low, medium, and high dose groups of YHTP (8.28, 16.56, and 33.12 g·kg-1), with 8 mice in each group. All groups, except the normal group, received intraperitoneal injections of lipopolysaccharide (LPS) and underwent chronic intermittent hypoxia (CIH) modeling for 4 weeks. Subsequently, the mice were treated with medications for 4 weeks and then sampled. Animal behavioral tests assessed memory impairment due to hypoxia. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to measure mRNA expression levels of M1-associated inflammatory factors interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and markers such as T lymphocyte activation antigen (CD86) and inducible nitric oxide synthase (iNOS), as well as M2-associated inflammatory factors interleukin-10 (IL-10), transforming growth factor-β (TGF-β), and the marker mannose receptor (CD206) in hippocampal tissue. Western blot was employed to detect differences in the expression of M1 and M2 microglia phenotypic markers (CD86, CD206) and glycolysis-related proteins glucose transporter type 1 (GLUT1), hexokinase 2 (HK2), phosphofructokinase (PFKM), pyruvate kinase 2 (PKM2), and monocarboxylic acid transporter 1 (MCT1). ResultBehavioral tests showed that compared to the results in the normal group, the Y-maze autonomous alternation rate was significantly reduced in the model group (P<0.01). The latency time for the target hole in the Barnes' maze during the training period (days 2, 3, 4) and testing period (days 5, 12) was significantly increased (P<0.05, P<0.01). M1 glial cell markers CD86 and iNOS, as well as inflammatory factors IL-1β and TNF-α mRNA, were significantly elevated (P<0.01). In contrast, the mRNA expression of M2 glial cell markers IL-10, CD206, and TGF-β was significantly reduced (P<0.01). The protein expression of glycolytic proteins HK2, PFKM, PKM2, MCT1, and the M1 marker CD86 was significantly increased (P<0.05, P<0.01), while M2 marker CD206 protein expression was significantly decreased (P<0.01). Compared to the results in the model group, the Y-maze autonomous alternation rate was significantly increased in the medium and high dose groups of YHTP (P<0.05, P<0.01). The latency time for the target hole during the training (day 4) and testing periods (days 5, 12) was significantly reduced (P<0.01). Real-time PCR results indicated that mRNA expression levels of M1-related pro-inflammatory factors in the hippocampal tissue were significantly reduced in the low, medium, and high dose groups of YHTP (P<0.01), while M2-related inflammatory factors' mRNA expression was significantly increased (P<0.01). Western blot results showed that in the medium and high dose groups of YHTP, the expression of the M1 marker CD86 in the hippocampus was reduced, whereas the expression of the M2 marker CD206 was significantly increased (P<0.01), with a significant decrease in the expression of glycolysis-related proteins (P<0.01). ConclusionYHTP can improve inflammation and cognitive impairment induced by hypoxia in OSA model mice. This is achieved by downregulating glycolysis in brain microglia, inhibiting M1 activation, reducing pro-inflammatory factor release, and promoting M2 activation, thereby exerting a therapeutic effect on inflammation and cognitive impairment caused by OSA.
6.Comprehensive imaging diagnosis and comparative study of breast architectural distortion lesions
Yuhan BAI ; Jian YANG ; Zhiyan SONG ; Lin ZHANG ; Haifeng LIU ; Hongfen PENG ; Dongyou ZHANG
Journal of Practical Radiology 2024;40(6):913-916,930
Objective To analyze the characteristics of breast architectural distortion(AD)in mammography,MRI,and ultrasound,and to explore the value of each imaging examination in the diagnosis of AD lesions.Methods The mammography,ultrasound,and MRI data of 46 patients(48 lesions)with AD detected by mammography were analyzed retrospectively.Based on the pathological results,the imaging characteristics of benign and malignant AD were compared.Results The morphological and central density differences between benign and malignant lesions were statistically significant.There was no significant difference in microcalcification between benign and malignant AD.On 48 breast MRI,26 lesions showed mass enhancement,17 lesions showed non-mass enhancement,3 lesions showed punctate enhancement and 2 lesions showed no enhancement.There was no statistical significance in the distribution of enhancement types.The difference in time-signal intensity curve(TIC)types between benign and malignant AD was statistically significant.There was no statistical significance in ultrasound manifestation between benign and malignant AD.Using imaging findings greater than those in the breast imaging reporting and data system(BI-RADS)4 categories as a suspected malignant diagnosis,based on pathological examination results.The area under the curve(AUC)by mammography,ultrasound,and MRI was 0.582,0.426,and 0.764,respectively,showed significant differences in diagnostic efficiency.Conclusion MRI has higher sensitivity and specificity in detecting breast AD,which significantly improves the diagnosis coincidence rate of lesions,and can provide an important basis for clinicians to make decisions on surgical treatment.
7.Analysis factors influencing left ventricular thrombus in patients with non-ischemic heart failure
Zhiyan WANG ; Hao ZHANG ; Wenjie LI ; Chang HUA ; Yangyang TANG ; Xinru LIU ; Yuling XIONG ; Qiang LYU ; Jianzeng DONG ; Xin DU
Chinese Journal of Cardiology 2024;52(10):1155-1161
Objective:To explore the influencing factors of left ventricular thrombus (LVT) in patients with non-ischemic heart failure (NIHF) and to construct a nomogram prediction model for NIHF patients with LVT.Methods:This study was a case-control study. A total of 2 592 patients with NIHF hospitalized in Beijing Anzhen Hospital affiliated to Capital Medical University from January 2018 to July 2022 were selected. Fifty-one patients with LVT identified by echocardiography and cardiac magnetic resonance were classified into LVT group. One hundred and sixty patients were selected as the non-LVT group using a 1∶3 propensity score matching based on age and gender. Multivariate logistic regression analysis was used to explore the influencing factors of LVT in patients with NIHF. A nomogram prediction model was constructed, and the area under (AUC) the receiver operating characteristic (ROC) curve was calculated to evaluate the predictive effect of the model.Results:A total of 211 patients were enrolled, with a median age of 40 years old and 160 males (76%). Compared with non-LVT group, LVT group had lower systolic blood pressure ((112±20) mmHg vs. (120±19) mmHg; 1 mmHg=0.133 kPa), lower left ventricular ejection fraction (LVEF; (27±12)% vs. (39±14)% ), lower proportion of patients with history of hypertension (28% (14/51) vs. 44% (70/160)) and atrial fibrillation (8% (4/51)vs.39% (62/160)), higher proportion of patients with New York Heart Association functional class Ⅲ to Ⅳ (class Ⅲ: 59% (30/51) vs. 41% (66/160); class Ⅳ: 28% (14/51) vs. 19% (31/160)), and larger left ventricular end-systolic diameter (LVESD; (56±14) mm vs. (50±15) mm). The levels of hemoglobin ((152±23) g/L vs. (142±30) g/L), D-dimer (508 (300, 1 105) μg/L vs. 158 (68, 379) μg/L), and N-terminal pro-brain natriuretic peptide (3 429 (2 462, 4 734) ng/L vs. 1 288 (422, 2 544) ng/L) were higher in LVT group than in non-LVT group ( P all<0.05). LVT group had a higher proportion of patients using beta-blockers (92% (47/51) vs. 78% (124/160)), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors (88% (45/51) vs. 72% (115/160)), and anticoagulant drugs (98% (50/51) vs. 32% (51/160)) than non-LVT group (all P <0.05). Multivariate logistic regression showed that reduced LVEF ( OR=1.08, 95% CI 1.02-1.15, P=0.008), decreased LVESD ( OR=1.07, 95% CI 1.01-1.12, P=0.013), and increased D-dimer levels ( OR=5.40, 95% CI 1.98-14.74, P=0.001) were independent influencing factors for LVT in patients with NIHF. The ROC curve showed that the AUC of the nomogram for predicting LVT in patients with NIHF was 0.793 (95% CI 0.710-0.876, P<0.001). Conclusion:Reduced LVEF, decreased LVESD, and elevated D-dimer are associated with LVT in NIHF patients. The predictive model developed based on the above indicators has certain value in predicting LVT in NIHF patients.
8.Clinical Practice Guidelines for TCM in Children with Adenoidal Hypertrophy
Bin YUAN ; Zhiyan JIANG ; Huaan MA ; Mei HAN ; Zhuyun LIU ; Xianzhi REN ; Weiwei LI ; Sumei WANG ; Xueqing ZHANG ; Xiaohui ZHU ; Lei WANG ; Chanchan HU ; Jun MA ; Tianhan WANG ; Shuo LI
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(2):184-189
Literature related to children's adenoid hypertrophy was retrieved to form an expert questionnaire.According to the group standard writing rules of the China Association of Chinese Medicine,the peer consultation,quality evaluation and suitability eval-uation were completed through three rounds of Delphi expert questionnaire surveys and expert discussion meetings,and the Clinical Practice Guidelines for TCM in Children with Adenoidal Hypertrophy was finally formed.The guidelines have been formulated to clarify the scope of application of the guidelines,normative reference documents,terms and definitions,diagnosis,syndrome differentiation,treatment,prevention and care,and to provide an important reference for the clinical practice and diagnosis and treatment norms of tra-ditional Chinese medicine for children with adenoid hypertrophy.
9.Primary malignant giant cell tumor of bone with predominant osteosarcoma morphology:a clinicopathological analysis of seven cases
Ting JIANG ; Juan ZHOU ; Chunyan CHEN ; Yanrui PANG ; Lan SHEN ; Jie CHEN ; Zhiyan LIU
Chinese Journal of Clinical and Experimental Pathology 2024;40(8):807-812
Purpose To elucidate the clinicopathological characteristics of primary malignant giant cell tumor of bone(PMGCTB)with mainly osteosarcoma-like morphology.Meth-ods Clinicopathologic features of 7 cases of PMGCTB were ret-rospectively analyzed.Results Among 7 patients with PMGCTB,there were 4 females and 3 males,aged between 9 and 66 years(mean age 39.5 years,median age 35 years).The distal femur emerged as the most frequent site to be involved(3/6).The main clinical manifestations included pain and swelling at the original site of the tumor.Radiological findings indicated osteolytic lesions,often combined with sclerotic areas;most ca-ses showed cortical bone destruction and soft tissue masses(5/7).Histologically,the majority of tumors exhibited typical mor-phological features of osteosarcoma with a few or without osteo-clast-like multinucleated giant cells.Positive immunoreaction with H3F3A G34W was confirmed in 6 cases and with H3F3A G34V in 1 case.SATB2 and p63 were positive in all cases,p53 was proved to be wild type,the Ki67 proliferation index ranged approximately from 10%to 50%.H3F3A p.G34W mutation was detected in 6 cases and only 1 case harboring H3F3A p.G34V mutation.Conclusion PMGCTB is exceedingly rare and difficult for accurate diagnosis,especially for those with atypical morphological features.A comprehensive analysis involving ra-diological,immunophenotypic,and molecular detection is neces-sary to rule out other high-grade sarcomas.
10.Pediatric giant cell tumor of bone: a clinicopathological analysis of 35 cases
Yanrui PANG ; Juan ZHOU ; Chunyan CHEN ; Qianqian ZHAO ; Keyang SUN ; Zhiyan LIU
Chinese Journal of Pathology 2024;53(11):1122-1126
Objective:To investigate the clinicopathological characteristics of giant cell tumor of bone (GCTB) in children.Methods:A total of 35 cases of GCTB diagnosed at Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiaotong University School from 2016 to 2023 were collected, and a retrospective analysis of clinicopathological features and imaging findings was conducted.Results:Pediatric GCTB accounted for approximately 4.6% of total GCTB cases during the study period. There were 11 males and 24 females. The onset age ranged from 9 to 18 years (mean age 15 years, median age 16 years), with 8 cases (8/35, 22.9%) experiencing postoperative recurrence. Twenty-eight cases (28/35, 80%) primarily affected long bones, while 7 cases involved small or irregular bones. Imaging revealed osteolytic changes as the predominant feature, with 3 cases exhibited open physis, one of which had the tumor primarily at the diaphysis without crossing the physis. Histologically, pediatric GCTB resembled adult cases, characterized by mononuclear cells and osteoclast-like giant cells. Seven cases with denosumab treatment demonstrated degrees of giant cell disappearance, increased fibrous tissue and reactive bone proliferation in the stroma. One case was diagnosed as pediatric multicentric GCTB, and three cases as pediatric primary malignant GCTB, with malignant transformation into osteosarcoma. In all 35 cases, mutations in the H3F3A gene were identified, comprising 32 cases with H3.3 p.G34W mutations, one case with H3.3 p.G34V mutation, and 2 cases with H3.3 p.G34L mutations. Notably, the former two categories were successfully validated at the protein level through immunohistochemical staining, utilizing highly specific antibodies tailored for these mutation types: H3.3 p.G34W antibody and H3.3 p.G34V antibody. However, immunohistochemical staining was not available for the last category.Conclusions:Pediatric GCTB predominantly affects females and occurs primarily in long bones, mainly around the knee joint, the majority of tumors predominantly arise in the epiphysis and extend into the metaphysis; however, in cases where the epiphyseal plates are still unclosed, the tumors may be restricted to the metaphysis. Detection of H3F3A gene mutation is crucial for the diagnosis and differential diagnosis of pediatric GCTB.

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