1.Study on the mechanism of Buzhong Yiqi Decoction regulating macrophage polarization in mice with autoimmune thyroiditis
Lanting WANG ; Zhaohan ZHAI ; Shouxin JU ; Liang KONG ; Jie DING ; Yao XIAO ; Yiran CHEN ; Zhimin WANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):529-541
Objective:
To explore the mechanism of Buzhong Yiqi Decoction in modulating macrophage polarization and intervening in autoimmune thyroiditis (AIT) mice.
Methods:
Using the random number table method, 48 SPF-grade NOD.H-2h4 mice were assigned to the normal, model, low-dose (4.10 g/kg), medium-dose (8.19 g/kg), high-dose group (16.38 g/kg) of Buzhong Yiqi Decoction, and selenium yeast tablet (0.026 mg/kg) groups, with eight mice in each group. All groups, except the normal group, were free to drink high iodine water (0.05% sodium iodide) to prepare AIT mouse models for 8 consecutive weeks. After the modeling was complete, each treatment group was orally administered with the corresponding medication, while the normal and model groups were orally administered with an equal volume of distilled water once a day for 8 consecutive weeks. High-performance liquid chromatography with an oscillometric refractive detector was used to analyze the content of Astragaloside Ⅳ in Buzhong Yiqi Decoction. Hematoxylin and eosin staining was used to observe the pathological morphology of mouse thyroid tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum thyroid peroxidase antibody (TPO-Ab), thyroglobulin antibody (TgAb), interleukin (IL)-6, IL-10, and tumor necrosis factor-α (TNF-α). An immunofluorescence assay was used to detect the positive area percentage of M1 and M2 macrophages in mouse thyroid tissue. Flow cytometry assay was used to detect macrophage polarization in mouse spleen tissue. Real-time fluorescence quantitative PCR was used to detect the mRNA expression of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), nuclear factor kappa B inhibitory protein α (IκBα), and nuclear factor-κB (NF-κB) p65 in mouse spleen tissue. Western blotting was used to detect the expression of the phosphorylated IκBα (p-IκBα), phosphorylated NF-κB p65 (p-NF-κB p65), and NLRP3 protein in mouse spleen tissue.
Results:
The content of Astragaloside Ⅳ in Buzhong Yiqi Decoction was (7.09±0.06) g/L. Compared to the normal group, significant lymphocyte infiltration was observed in the thyroid tissue of mice in the model group. The levels of serum TPO-Ab, TgAb, IL-6, and TNF-α increased (P<0.05). The positive area percentage of M1 macrophages in thyroid tissue increased (P<0.05). The proportion of M1 macrophages and M1/M2 in spleen tissue increased (P<0.05). The relative expression levels of NF-κB p65 and NLRP3 mRNA in spleen tissue increased (P<0.05). The relative expression of p-IκBα, p-NF-κB p65, and NLRP3 proteins increased (P<0.05). Compared to the model group, the inflammation infiltration degree in the thyroid tissue of mice in each dose group of Buzhong Yiqi Decoction and selenium yeast tablet group was reduced, the serum TPO-Ab, TgAb, IL-6, TNF-α content was decreased, the spleen tissue M1/M2 was reduced, the expression of NF-κB p65 mRNA was reduced, and the relative expression levels of p-IκBα, p-NF-κB p65 protein were reduced (P<0.05). The Buzhong Yiqi Decoction high-dose and selenium yeast tablets groups showed an increase in IL-10 content, an increase in positive area percentage of M2 macrophages in thyroid tissue, an increase in M2 macrophages proportion in spleen tissue, and a decrease in NLRP3 mRNA and protein relative expression levels (P<0.05).
Conclusion
Buzhong Yiqi Decoction may regulate macrophage polarization by inhibiting the NF-κB/NLRP3 signaling pathway, thus improving the inflammatory damage in mice with AIT.
2.Clinicopathological characteristics and prognosis of papillary renal neoplasm with reverse polarity
Zhuolong WU ; Zaoyu WANG ; Qiong CHEN ; Wen KONG ; Jiwei HUANG ; Jin ZHANG ; Yonghui CHEN ; Yiran HUANG ; Wei XUE
Chinese Journal of Urology 2024;45(3):175-179
Objective:To summarize the clinical and pathological characteristics, treatment methods, and prognosis of papillary renal neoplasm with reverse polarity (PRNRP).Methods:The clinical and pathological data of six pathologically confirmed PRNRP patients admitted to Renji Hospital affiliated with Shanghai Jiaotong University School of Medicine from August 2022 to August 2023 were retrospectively analyzed. Among them, three were male and three were female, with an average age of (55.3±10.5) years old. All six cases were incidentally discovered during health examinations. Preoperative contrast-enhanced CT scans showed tumors with cortical phase manifestations of uneven enhancement, avascularity, and indistinct borders, with CT values of (85.6±18.7) HU. In the corticomedullary phase, the CT values showed mild elevation, with an average of (94.3±4.7) HU. In the delayed phase, the tumor boundaries were clear, and the enhancement degree was significantly lower than that of the surrounding renal cortex and medulla, with a tumor CT value of (86.3±11.9) HU. The pseudocapsule of the tumor was not clearly displayed on contrast-enhanced CT scans. All cases underwent partial nephrectomy, including two cases of robot-assisted laparoscopic partial nephrectomy and four cases of laparoscopic partial nephrectomy.Results:Postoperative pathological measurements revealed a maximum tumor diameter ranging from 6 to 15 mm, with an average diameter of (11.0±3.5) mm. All six cases were classified as pT 1aN 0M 0 stage. Microscopically, the tumors exhibited branching papillary structures with eosinophilic cytoplasm, and the tumor cells displayed low-grade nuclei located at the top of the cytoplasm and away from the basal membrane. Immunohistochemical analysis showed diffuse strong positivity for GATA3 and CK7, while CA-Ⅸ expression was negative. The median follow-up time after surgery was 10(9, 13) months, and no tumor recurrence or metastasis was observed. Conclusions:PRNRP is a rare, low-grade malignant papillary renal tumor. Contrast-enhanced CT scan has characteristic features of avascularity. Pathological morphological features are low-grade nuclei located at the top of the cytoplasm and far away from the basal membrane, forming a "reverse polarity". The immunophenotype shows positive expression of GATA3 and CK7. Partial nephrectomy is the recommended treatment approach, and the postoperative prognosis is favorable.
3. Surgical management for local retroperitoneal recurrence of 33 renal cell carcinoma patients underwent radical nephrectomy
Jiwei HUANG ; Wen CAI ; Wen KONG ; Jin ZHANG ; Yonghui CHEN ; Yiran HUANG
Chinese Journal of Oncology 2019;41(9):703-707
Objective:
To investigate the therapeutic effects of surgical management for local retroperitoneal recurrence of renal cell carcinoma after radical nephrectomy.
Methods:
Clinical and follow-up data of 33 cases of local recurrence after radical nephrectomy in Renji Hospital from January 2010 to April 2018 were retrospectively analyzed.
Results:
In these 33 patients, 25 was male and 8 was female; The median age was 54 years old. The pathological stage of radical nephrectomy included 14 cases of pT1-2N0M0 stage, 16 cases of pT3-4 N0M0 stage, and 3 cases of pN1 stage. Only 4 relapsing patients had symptoms, the others were all found to have recurrence by imaging examination during follow up period of postoperation.The median recurrence time for all patients was 30 months, and the median diameter of recurrent tumors was 4.5 cm.Twenty-nine patients underwent complete resection of local recurrent lesions, and 4 patients whose recurrent lesions could not be completely resected converted receive palliative surgery. The median intraoperative blood loss was 500 ml and the median hospital stay after surgery was 4 days. Clavien grade Ⅰ-Ⅱ complications occurred in 5 patients after surgery, and no serious complications of Clavien grade Ⅲ-Ⅴ complications occurred. Six patients received postoperative adjuvant target therapy and distant metastasis occurred in one patient.In the 27 patients without adjuvant target therapy, postoperative distant metastases occurred in 12 patients. The median survival time for all patients after local recurrence surgery was 31 months. The 1-year and 3-year survival rates were 86.8% and 36.9%, respectively.
Conclusions
The rigorous imaging examination after radical nephrectomy can detect local recurrent lesions as early as possible in most relapsing patients and imaging examination can predict the integrity of surgical resection of local recurrence.Although intraoperative bleeding of resection of local recurrence is relatively high, the operation is safe and the postoperative complications are controllable. Postoperative adjuvant therapy may also provide better survival benefit for patients with local recurrence.
4.LSD1 inhibition suppresses the growth of clear cell renal cell carcinoma upregulating P21 signaling.
Liangsong ZHU ; Jianfeng WANG ; Wen KONG ; Jiwei HUANG ; Baijun DONG ; Yiran HUANG ; Wei XUE ; Jin ZHANG
Acta Pharmaceutica Sinica B 2019;9(2):324-334
Histone lysine-specific demethylase 1 (LSD1) has been implicated in the disease progression of several types of solid tumors. This study provides the first evidence showing that LSD1 overexpression occurred in 62.6% (224/358) of clear cell renal cell carcinomas (ccRCC). LSD1 expression was associated with the progression of ccRCC, as indicated by TNM stage (=0.006), especially tumor stage (=0.017) and lymph node metastasis (=0.030). High LSD1 expression proved to be an independent prognostic factor for poor overall survival (<0.001) and recurrence-free survival (<0.001) of ccRCC patients. We further show that LSD1 inhibition by siRNA knockdown or using the small molecule inhibitor SP2509 suppressed the growth of ccRCC and . Mechanistically, inhibition of LSD1 decreased the H3K4 demethylation at the gene promoter, which was associated with P21 upregulation and cell cycle arrest at G1/S in ccRCC cells. Our findings provide new mechanistic insights into the role of LSD1 in ccRCC and suggest the therapeutic potential of LSD1 inhibitors in ccRCC treatment.
5.Surgical management for local retroperitoneal recurrence of 33 renal cell carcinoma patients underwent radical nephrectomy
Jiwei HUANG ; Wen CAI ; Wen KONG ; Jin ZHANG ; Yonghui CHEN ; Yiran HUANG
Chinese Journal of Oncology 2019;41(9):703-707
Objective To investigate the therapeutic effects of surgical management for local retroperitoneal recurrence of renal cell carcinoma after radical nephrectomy. Methods Clinical and follow?up data of 33 cases of local recurrence after radical nephrectomy in Renji Hospital from January 2010 to April 2018 were retrospectively analyzed. Results In these 33 patients, 25 was male and 8 was female; The median age was 54 years old. The pathological stage of radical nephrectomy included 14 cases of pT1?2N0M0 stage, 16 cases of pT3?4 N0M0 stage, and 3 cases of pN1 stage. Only 4 relapsing patients had symptoms, the others were all found to have recurrence by imaging examination during follow up period of postoperation. The median recurrence time for all patients was 30 months, and the median diameter of recurrent tumors was 4.5 cm.Twenty?nine patients underwent complete resection of local recurrent lesions, and 4 patients whose recurrent lesions could not be completely resected converted receive palliative surgery. The median intraoperative blood loss was 500 ml and the median hospital stay after surgery was 4 days. Clavien gradeⅠ?Ⅱ complications occurred in 5 patients after surgery, and no serious complications of Clavien grade Ⅲ?Ⅴcomplications occurred. Six patients received postoperative adjuvant target therapy and distant metastasis occurred in one patient.In the 27 patients without adjuvant target therapy, postoperative distant metastases occurred in 12 patients. The median survival time for all patients after local recurrence surgery was 31 months. The 1?year and 3?year survival rates were 86.8% and 36.9%, respectively. Conclusions The rigorous imaging examination after radical nephrectomy can detect local recurrent lesions as early as possible in most relapsing patients and imaging examination can predict the integrity of surgical resection of local recurrence.Although intraoperative bleeding of resection of local recurrence is relatively high, the operation is safe and the postoperative complications are controllable. Postoperative adjuvant therapy may also provide better survival benefit for patients with local recurrence.
6.Surgical management for local retroperitoneal recurrence of 33 renal cell carcinoma patients underwent radical nephrectomy
Jiwei HUANG ; Wen CAI ; Wen KONG ; Jin ZHANG ; Yonghui CHEN ; Yiran HUANG
Chinese Journal of Oncology 2019;41(9):703-707
Objective To investigate the therapeutic effects of surgical management for local retroperitoneal recurrence of renal cell carcinoma after radical nephrectomy. Methods Clinical and follow?up data of 33 cases of local recurrence after radical nephrectomy in Renji Hospital from January 2010 to April 2018 were retrospectively analyzed. Results In these 33 patients, 25 was male and 8 was female; The median age was 54 years old. The pathological stage of radical nephrectomy included 14 cases of pT1?2N0M0 stage, 16 cases of pT3?4 N0M0 stage, and 3 cases of pN1 stage. Only 4 relapsing patients had symptoms, the others were all found to have recurrence by imaging examination during follow up period of postoperation. The median recurrence time for all patients was 30 months, and the median diameter of recurrent tumors was 4.5 cm.Twenty?nine patients underwent complete resection of local recurrent lesions, and 4 patients whose recurrent lesions could not be completely resected converted receive palliative surgery. The median intraoperative blood loss was 500 ml and the median hospital stay after surgery was 4 days. Clavien gradeⅠ?Ⅱ complications occurred in 5 patients after surgery, and no serious complications of Clavien grade Ⅲ?Ⅴcomplications occurred. Six patients received postoperative adjuvant target therapy and distant metastasis occurred in one patient.In the 27 patients without adjuvant target therapy, postoperative distant metastases occurred in 12 patients. The median survival time for all patients after local recurrence surgery was 31 months. The 1?year and 3?year survival rates were 86.8% and 36.9%, respectively. Conclusions The rigorous imaging examination after radical nephrectomy can detect local recurrent lesions as early as possible in most relapsing patients and imaging examination can predict the integrity of surgical resection of local recurrence.Although intraoperative bleeding of resection of local recurrence is relatively high, the operation is safe and the postoperative complications are controllable. Postoperative adjuvant therapy may also provide better survival benefit for patients with local recurrence.
7. Comparison of efficacy between sorafenib and sunitinib as first-line therapy for metastatic renal cell carcinoma and analyze prognostic factors for survival
Wen CAI ; Yichu YUAN ; Mingyang LI ; Wen KONG ; Baijun DONG ; Yonghui CHEN ; Jin ZHANG ; Wei XUE ; Yiran HUANG ; Lixin ZHOU ; Jiwei HUANG
Chinese Journal of Oncology 2018;40(5):384-389
Objective:
To investigate the efficacy and drug related adverse reactions of sorafenib and sunitinib as first-line tyrosine-kinase inhibitors (TKIs) for patients with metastatic renal cell carcinoma (mRCC) and analyze the clinical prognostic factor for survival.
Methods:
The data of 271 patients with metastatic renal cell carcinoma who had complete clinicopathological data were retrospectively analyzed, including 174 cases in sorafenib group and 97 cases in sunitinib group, to access patients′ overall survival (OS) and progression-free survival (PFS). Prognostic values of all characteristics were determined by using univariate and multivariate Cox regression models.
Results:
The objective response rates (ORR) of the sorafenib and sunitinib groups were 14.9% and 19.6%, respectively, and the disease control rates (DCR) were 85.1% and 88.6%, respectively. No significant difference was found between the sorafenib and sunitinib group in ORR (
8.Effect of silencing UHRF1 on proliferation and metastasis of breast cancer cells
Practical Oncology Journal 2017;31(6):512-518
Objective The objective of this study was to investigate the effect of UHRF1 on the prolifer-ation and metastasis of breast cancer MDA-MB-231 cells and its mechanism. Methods The effect of silen-cing UHRF1 gene on the viability of MDA-MB-231 cells was detected by MTT assay. Colony formation assay was performed to analyze the effect of silencing UHRF1 on cell survival of MDA-MB-231 cells. The effect of silencing UHRF1 on the apoptosis of MDA-MB-231 cells was detected by acridine orange-ethidium bromide ( AO / EB) . Caspase-3 activity kit was used to detect the expression of caspase-3 in MDA-MB-231 cells. The expressions of Bcl-2,Bax,Bad,p-Bad,XIAP,p53,p21Cip1/Waf and p16INK4a were detectedby Western blot. The abilities of invasion and migration of MDA-MB-231 cells silenced by UHRF1were examined by Transwell and Wound healing assays,respectively. Results Silencing UHRF1 significantlydecreased the viability of MDA-MB-231 cells. Silencing UHRF1 decreased colony formation in MDA-MB-231 cells. Depletion of UHRF1 resulted in apoptosis inducedin MDA-MB-231 cells,showing nuclear morphological changes by AO/EB stai-ning and increasing caspase -3 activity. After knockdown of UHRF1,the expression of Bad,XIAP,Bax,p53, p21Cip1/Waf1 and p16INK4a was up-regulatedand down-regulated the expression of p-Bad and Bcl-2 in MDA-MB-231 cells. Transwell and wound healing assays demonstrated that silencing UHRF1 could decrease metasta-sisin MDA-MB-231 cells. Conclusion Silencing UHRF1 can inhibit the viability and survival of MDA-MB-231 cells,and inhibit the invasion and migration of MDA - MB -231 cells regulated by p53/p21Cip1/Waf1/p16INK4asignalings.
9.Discuss about the anesthesiology rotation of residency training for non-anesthesia specialty residents
Ye ZHANG ; Lihua JIANG ; Yiran KONG ; Zhuo CHEN ; Guonian WANG
Chinese Journal of Medical Education Research 2017;16(11):1171-1174
In order to improve the training quality of non anesthesiology professional physicians in anesthesiology department, the anesthesia department of Cancer Hospital affiliated to Harbin Medical Uni-versity Anesthesiology summed up the problems existing in the rotation process of anesthesiology depart-ment in the past, and explored the aesthesia teaching of the standardized doctors. We also improved the teachers' and students' awareness of the importance of anesthesiology learning, formulated standardized training programs, stimulated the interest of residents and teachers, strengthened teachers' teaching ability and teaching consciousness, Through the use of special lectures, case teaching, problem based teaching, we constructed diversified teaching to enhance the students' mastery of knowledge and skills in anesthesiology, and added purposeful examination at the end of rotation. As a result, the quality of anesthesiology rotation of non-anesthesia specialty residents was improved.
10.Association of post-treatment hypoalbuminemia and survival in Chinese patients with metastatic renal cell carcinoma
Cai WEN ; Zhang JIN ; Chen YONGHUI ; Kong WEN ; Huang YIRAN ; Huang JIWEI ; Zhou LIXIN
Chinese Journal of Cancer 2017;36(7):315-325
Background: Hypoalbuminemia adversely affects the clinical outcomes of various cancers. The purpose of this study was to estimate the prognostic value of hypoalbuminemia 3–5 weeks after treatment in patients with metastatic renal cell carcinoma (mRCC) who received sorafenib or sunitinib as first-line treatment. Methods: In this single-center, retrospective study, we assessed the progression-free survival (PFS) and overall sur-vival (OS) of 184 mRCC patients who received first-line sorafenib or sunitinib treatment. PFS and OS were compared between patients with post-treatment hypoalbuminemia (post-treatment albumin level <36.4 g/L) and those with normal post-treatment albumin level (albumin level ≥36.4 g/L). The Memorial Sloan Kettering Cancer Center (MSKCC)risk model stratified mRCC patients into three risk categories. Prognostic values of all patient characteristics including MSKCC risk category were determined by using univariate and multivariate Cox regression models. Prognostic value was further determined using the Harrell concordance index and receiver operating characteristic curve analysis. Results: The median PFS and OS of the 184 patients were 11 months (95% confidence interval [CI] 9–12 months) and 23 months (95% CI 19–33 months), respectively. Patients with post-treatment hypoalbuminemia had significantly shorter median PFS (6 months [95% CI 5–7 months]) and OS (11 months [95% CI 9–15 months]) than patients who had normal post-treatment albumin levels (PFS: 12 months [95% CI 11–16 months], P < 0.001; OS: 31 months [95% CI 24–42 months], P < 0.001), respectively. Multivariate analysis showed that post-treatment hypoalbuminemia was an independent predictor of PFS (hazard ratio [HR], 2.113; 95% CI 1.390–3.212; P < 0.001) and OS (HR, 2.388; 95% CI 1.591–3.585; P < 0.001). Post-treatment hypoalbuminemia could also be combined with the MSKCC risk category for better prediction about OS. The model that included post-treatment hypoalbuminemia and MSKCC risk category improved the predictive accuracy for PFS and OS (c-index: 0.68 and 0.73, respectively) compared with the basic MSKCC risk model (c-index: 0.67 and 0.70, respectively). The prognostic values for PFS and OS of the integrated MSKCC risk model involving post-treatment hypoalbuminemia were significantly more accurate than the basic MSKCC risk model using likelihood ratio analysis (both P < 0.001). Conclusions: Post-treatment hypoalbuminemia can be considered an independent prognostic factor for patients with mRCC who undergo first-line treatment with tyrosine kinase inhibitors. Additionally, integrating post-treatment serum albumin level into the basic MSKCC risk model can improve the accuracy of this model in predicting patient overall survival and progression-free survival.


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