1.Enhanced radiotheranostic targeting of integrin α5β1 with PEGylation-enabled peptide multidisplay platform (PEGibody): A strategy for prolonged tumor retention with fast blood clearance.
Siqi ZHANG ; Xiaohui MA ; Jiang WU ; Jieting SHEN ; Yuntao SHI ; Xingkai WANG ; Lin XIE ; Xiaona SUN ; Yuxuan WU ; Hao TIAN ; Xin GAO ; Xueyao CHEN ; Hongyi HUANG ; Lu CHEN ; Xuekai SONG ; Qichen HU ; Hailong ZHANG ; Feng WANG ; Zhao-Hui JIN ; Ming-Rong ZHANG ; Rui WANG ; Kuan HU
Acta Pharmaceutica Sinica B 2025;15(2):692-706
Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [64Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [64Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [64Cu]QM-2303 from the bloodstream. Administration of a single dose of [177Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [64Cu]/[177Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [64Cu]/[177Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.
2.Cannabinoid receptor 1 promotes M1 polarization of macrophages through the Gαi/o/RhoA signaling pathway in mice with acute lung injury
Xiuzhen MA ; Ni ZHOU ; Siqi GUO ; Yuanyuan WANG ; Ping MAI
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(2):161-168
Objective·To explore the effects and potential molecular mechanisms of blocking cannabinoid receptor 1(CB1)in acute lung injury(ALI)in mice.Methods·Forty mice were randomly divided into blank control group,AM281(CB1 antagonist)control group,lipopolysaccharide(LPS)group,and LPS+AM281 group,with ten mice in each group.ALI models were induced by LPS.The pathological manifestations of lung tissues were observed in each group of mice by hematoxylin and eosin(H-E)staining and the inflammation scores were calculated.The mRNA levels of M1 markers[tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-12]and M2 markers[arginase(Arg),mannose receptor,C type 2(Mrc2),macrophage galactose-type lectin 1(Mgl1)]in lung macrophages were measured by reverse transcription and real-time fluorescence quantitative polymerase chain reaction(qPCR).Human myeloid leukemia monocytes THP-1 cells were cultured in vitro,and the expression of CB1 and CB2 in THP-1 cells was detected by immunofluorescence.After further blocking CB1 and inhibiting the Gαi/o/RhoA signaling pathway,the mRNA levels of M1 markers were assessed.Results·The LPS group showed significant lung tissue damage and a significant increase in inflammation scores in mice.After blocking CB1,compared with the LPS group,the LPS+AM281 group of mice showed improvements in lung injury,manifested as improved congestion of alveolar wall capillaries,reduced infiltration of inflammatory cells in the lung interstitium and alveolar cavity,and a decreased inflammation score(P=0.007).Compared with the control group,the levels of M1 marker in the lung tissue of the LPS group were upregulated,while the polarization of macrophages changed and the M1/M2 ratio was reversed after blocking CB1(all P<0.05).In vitro studies found that macrophages expressed CB1 and CB2.Activation of CB1 by arachidonyl-2-chloroethylamide(ACEA)upregulated the expression of M1 markers.Blocking CB1 and selectively inhibiting Gαi/o/RhoA signaling significantly downregulated M1 markers(all P<0.05).Conclusion·CB1 promotes the polarization of macrophage towards the M1 phenotype through the Gαi/o/RhoA signaling pathway in ALI,and blocking CB1 can improve lung injury.
3.Analysis of the clinical efficacy of robot-assisted radical resection for hilar cholangiocarcinoma
Dali BAO ; Guangchao YANG ; Zhongyu LI ; Bing YIN ; Shounan LU ; Yue MA ; Siqi LI ; Linqiang LI ; Bei SUN ; Hongchi JIANG ; Yong MA
Chinese Journal of Surgery 2025;63(6):515-522
Objective:To investigate the feasibility and therapeutic efficacy of robot-assisted radical resection for hilar cholangiocarcinoma.Methods:This is a retrospective case series study. The clinical data of 29 patients who underwent robot-assisted radical resection for hilar cholangiocarcinoma at the Department of Minimally Invasive Hepatic Surgery,the First Affiliated Hospital of Harbin Medical University from July 2021 to February 2025 were retrospectively collected. There were 16 males and 13 females, aged ( M(IQR)) 68.0 (10.0) years (range:36 to 78 years), and body mass index (24.0±2.9) kg/m 2 (range:17.5 to 29.1 kg/m 2). Bismuth-Corlette classification: 12 cases type Ⅰ, 4 cases type Ⅱ, 6 cases type Ⅲb, and 7 cases type Ⅳ. Preoperative CA19-9 was 161.7(320.9) U/ml (range:7.1 to 1 000.0 U/ml), and carcinoembryonic antigen was 2.8(2.1)μg/L (range:0.3 to 203.1 μg/L). Preoperative total bilirubin was 134.2 (348.9) μmol/L (range:10.4 to 557.9 μmol/L), direct bilirubin was 90.8 (264.1) μmol/L (range:2.5 to 418.7 μmol/L), ALT was 136.4 (134.8) U/L (range:13.0 to 569.9 U/L), AST was 122.2 (119.9) U/L (range:16.0 to 384.0 U/L), and albumin was (34.5±6.3) g/L (range:21.7 to 41.3 g/L). Comparison of quantitative data at different time points using paired t-test or Mann-Whitney U test. Cox univariate analysis was performed for the relevant variables, and Cox multivariate regression analysis was used to screen the independent prognostic factors of patients after robot-assisted radical resection for hilar cholangiocarcinoma. Results:All the 29 patients successfully underwent robot-assisted radical resection of hilar cholangiocarcinoma, and the R0 resection rate was 93.1% (27/29) without conversion to laparotomy. The operation time was 295.0 (87.5) minutes (range:195 to 590 minutes), the intraoperative blood loss was 100.0 (150.0) ml (range:20 to 1 000 ml), the intraoperative blood transfusion rate was 20.1% (6/29), the number of lymph nodes dissected was 10.0 (7.0) pieces (range: 6 to 18 pieces), the first postoperative deflatus time was 3.0 (1.0) days (range:2 to 4 days), The oral feeding time was 5.0 (1.0) days (range: 4 to 7 days), the drainage tube removal time was 8.0 (2.0) days (range: 6 to 26 days), and the postoperative hospital stay time was 10.0 (6.0) days (range:7 to 27 days). The incidence of complications above grade Ⅱ of the Clavien-Dindo complication grading system was 24.1% (7/29), including 3 cases of gastrointestinal bleeding with recurrent high fever, 1 case of delayed gastric emptying, 1 case of bile leakage, and 5 cases of hypoalbuminemia. The total bilirubin was 42.8 (66.8) μmol/L (range:6.8 to 195.9 μmol/L), direct bilirubin was 28.1 (38.5) μmol/L (range:4.3 to 88.6 μmol/L), ALT was 55.8 (56.0) U/L (range:9.9 to 207.1 U/L), AST was 33.9 (17.9) U/L (range:10.6 to 122.7 U/L), and albumin was (32.1±3.8) g/L (range:22.8 to 37.7 g/L), the levels of transaminase and bilirubin in the postoperative liver function indexes were significantly improved compared with those before operation, and the differences were statistically significant (all P<0.05). The mortality rate of patients without perioperative death was 3.4% (1/29) at 90 days after surgery. The results of Cox multivariate regression analysis showed that R0 resection was an independent prognostic factor for survival at 1 year after surgery ( P<0.05). The follow-up time was 15.0 (12.0) months (range:6 to 30 months), 1 of the 29 patients died of intra-abdominal infection 1 week after discharge, and the remaining 28 patients were completely followed up, of which 20 patients had no recurrence and metastasis during the follow-up period, and the tumor-free survival was 15.0 (12.0) months (range:6 to 30 months), the tumor-free survival rate was 65.5% (19/29), the overall survival rate was 68.9% (20/29), and 8 patients with postoperative recurrence and metastasis. One patient with liver metastasis survived after reoperation, and one patient underwent postoperative chemoradiotherapy and died due to recurrence. There were 8 deaths during the follow-up, of which 7 died due to tumor recurrence and metastasis, and 1 died due to previous underlying diseases. Conclusion:Robot-assisted radical resection for hilar cholangiocarcinoma is feasible and effective.
4.Mechanism of IGF2BP2 regulation of PPAR-γ/GLUT4 pathway in insulin resistance induced by sodium arsenite exposure in HepG2 cells
Shiqing XU ; Zhida HU ; Qiyao ZHANG ; Siqi ZHAO ; Yujie WANG ; Xiaohui WANG ; Teng MA ; Li WANG
Journal of Environmental and Occupational Medicine 2025;42(4):400-407
Background Arsenic is an environmentally harmful substance that causes hepatic insulin resistance and liver damage, increasing the risk of type 2 diabetes mellitus. Objective To explore whether the insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) is involved in insulin resistance in HepG2 cells after arsenic exposure through the peroxisome-proliferator-activated receptor γ (PPAR-γ) / glucose transporter 4 (GLUT4) pathway. Methods Cell viability was determined using cell counting kit 8 (CCK8) and an appropriate NaAsO2 infection dose was determined. A cellular arsenic exposure model of HepG2 cells was established by four concentrations of NaAsO2 solution for 24 h (the experiment was divided into four groups: 0, 2, 4, and 8 μmol·L−1); HepG2 cells were firstly treated with pcDNA3.1-IGF2BP2 and pcDNA3.1-NC respectively for 6 h, then with 8 μmol·L−1 NaAsO2 for 24 h to establish a IGF2BP2 overexpression cell model (the experiment was divided into 4 groups: control, NaAsO2, NaAsO2+pcDNA3.1-IGF2BP2, and NaAsO2+pcDNA3.1-NC); finally the cells were subject to 100 nmol·L−1 insulin stimulation for 30 min. Glycogen and glucose in HepG2 cells were determined by glycogen and glucose assay kits; mRNA expression levels of IGF2BP2 were measured by quantitative real-time PCR; protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in HepG2 were detected by Western blot (WB); and the binding of IGF2BP2 to PPAR-γ and PPAR-γ to GLUT4 was verified by co-immunoprecipitation (CO-IP) experiment. Results The results of CCK8 experiment showed a dose-effect relationship between NaAsO2 concentration and cell viability. When the concentration of NaAsO2 was ≥4 μmol·L−1 , the cell viabilities were lower than that of the control group (P <0.05). With the increasing dose of NaAsO2 infection, reduced glucose consumption and glycogen levels in HepG2 cells were found in the 2, 4, and 8 μmol·L−1 NaAsO2 treatment groups compared to the control group (P <0.05). The difference between the mRNA expression level of IGF2BP2 in the HepG2 cells treated with 4 or 8 μmol L−1 NaAsO2 and the control group was significant (P <0.05). In the IGF2BP2 overexpression cell model, compared with the control group, glucose consumption and glycogen levels were lowered in the NaAsO2 group (P <0.05), the mRNA expression level of IGF2BP2 and the protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in the cell membrane were all decreased (P <0.05). Compared with the NaAsO2 group, the glucose consumption and glycogen levels were increased in the NaAsO2+pcDNA3.1-IGF2BP2 group (P <0.05), and the mRNA expression level of IGF2BP2 and the protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in the cell membrane were all increased (P <0.05). The results of CO-IP experiments showed that IGF2BP2 interacted with PPAR-γ as well as PPAR-γ with GLUT4 protein. Conclusion IGF2BP2 is involved in arsenic exposure-induced insulin resistance in HepG2 cells by acting on the PPAR-γ/GLUT4 pathway.
5.Determination of urinary perchlorate content and normal reference range of urinary perchlorate in primary school students
Lyu SHANG ; Mengdie SHI ; Hongfei MA ; Siqi ZHAO ; Xiao WANG
Journal of Public Health and Preventive Medicine 2025;36(5):59-62
Objective To explore the normal reference range of perchlorate content in the urine of primary school students, and compare whether there are differences in their urine perchlorate contents among different populations, and to provide reference for the health care of primary school students. Methods A total of 441 primary school students aged 6 to 15 years old in a certain city were selected, and their urine samples were collected. The contents of perchlorate in the urine were determined by ultra-high performance liquid chromatography coupled with mass spectrometry, and the measurement data was statistically analyzed using SPSS software. Results There was no significant gender difference in the content of perchlorate in the urine of primary school students, but there was an age difference. The normal reference range for the content of perchlorate in the urine of primary school students aged 6-9 years old was 0-99.09 μg/L, and the normal reference range for the content of perchlorate in the urine of primary school students aged 10-15 years old was 0-74.56 μg/L. Conclusion Through the measurement and analysis of a large number of samples, a normal reference range for the content of urinary perchlorate in primary school students have been recommended.
6.Cannabinoid receptor 1 promotes M1 polarization of macrophages through the Gαi/o/RhoA signaling pathway in mice with acute lung injury
Xiuzhen MA ; Ni ZHOU ; Siqi GUO ; Yuanyuan WANG ; Ping MAI
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(2):161-168
Objective·To explore the effects and potential molecular mechanisms of blocking cannabinoid receptor 1(CB1)in acute lung injury(ALI)in mice.Methods·Forty mice were randomly divided into blank control group,AM281(CB1 antagonist)control group,lipopolysaccharide(LPS)group,and LPS+AM281 group,with ten mice in each group.ALI models were induced by LPS.The pathological manifestations of lung tissues were observed in each group of mice by hematoxylin and eosin(H-E)staining and the inflammation scores were calculated.The mRNA levels of M1 markers[tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-12]and M2 markers[arginase(Arg),mannose receptor,C type 2(Mrc2),macrophage galactose-type lectin 1(Mgl1)]in lung macrophages were measured by reverse transcription and real-time fluorescence quantitative polymerase chain reaction(qPCR).Human myeloid leukemia monocytes THP-1 cells were cultured in vitro,and the expression of CB1 and CB2 in THP-1 cells was detected by immunofluorescence.After further blocking CB1 and inhibiting the Gαi/o/RhoA signaling pathway,the mRNA levels of M1 markers were assessed.Results·The LPS group showed significant lung tissue damage and a significant increase in inflammation scores in mice.After blocking CB1,compared with the LPS group,the LPS+AM281 group of mice showed improvements in lung injury,manifested as improved congestion of alveolar wall capillaries,reduced infiltration of inflammatory cells in the lung interstitium and alveolar cavity,and a decreased inflammation score(P=0.007).Compared with the control group,the levels of M1 marker in the lung tissue of the LPS group were upregulated,while the polarization of macrophages changed and the M1/M2 ratio was reversed after blocking CB1(all P<0.05).In vitro studies found that macrophages expressed CB1 and CB2.Activation of CB1 by arachidonyl-2-chloroethylamide(ACEA)upregulated the expression of M1 markers.Blocking CB1 and selectively inhibiting Gαi/o/RhoA signaling significantly downregulated M1 markers(all P<0.05).Conclusion·CB1 promotes the polarization of macrophage towards the M1 phenotype through the Gαi/o/RhoA signaling pathway in ALI,and blocking CB1 can improve lung injury.
7.Analysis of the clinical efficacy of robot-assisted radical resection for hilar cholangiocarcinoma
Dali BAO ; Guangchao YANG ; Zhongyu LI ; Bing YIN ; Shounan LU ; Yue MA ; Siqi LI ; Linqiang LI ; Bei SUN ; Hongchi JIANG ; Yong MA
Chinese Journal of Surgery 2025;63(6):515-522
Objective:To investigate the feasibility and therapeutic efficacy of robot-assisted radical resection for hilar cholangiocarcinoma.Methods:This is a retrospective case series study. The clinical data of 29 patients who underwent robot-assisted radical resection for hilar cholangiocarcinoma at the Department of Minimally Invasive Hepatic Surgery,the First Affiliated Hospital of Harbin Medical University from July 2021 to February 2025 were retrospectively collected. There were 16 males and 13 females, aged ( M(IQR)) 68.0 (10.0) years (range:36 to 78 years), and body mass index (24.0±2.9) kg/m 2 (range:17.5 to 29.1 kg/m 2). Bismuth-Corlette classification: 12 cases type Ⅰ, 4 cases type Ⅱ, 6 cases type Ⅲb, and 7 cases type Ⅳ. Preoperative CA19-9 was 161.7(320.9) U/ml (range:7.1 to 1 000.0 U/ml), and carcinoembryonic antigen was 2.8(2.1)μg/L (range:0.3 to 203.1 μg/L). Preoperative total bilirubin was 134.2 (348.9) μmol/L (range:10.4 to 557.9 μmol/L), direct bilirubin was 90.8 (264.1) μmol/L (range:2.5 to 418.7 μmol/L), ALT was 136.4 (134.8) U/L (range:13.0 to 569.9 U/L), AST was 122.2 (119.9) U/L (range:16.0 to 384.0 U/L), and albumin was (34.5±6.3) g/L (range:21.7 to 41.3 g/L). Comparison of quantitative data at different time points using paired t-test or Mann-Whitney U test. Cox univariate analysis was performed for the relevant variables, and Cox multivariate regression analysis was used to screen the independent prognostic factors of patients after robot-assisted radical resection for hilar cholangiocarcinoma. Results:All the 29 patients successfully underwent robot-assisted radical resection of hilar cholangiocarcinoma, and the R0 resection rate was 93.1% (27/29) without conversion to laparotomy. The operation time was 295.0 (87.5) minutes (range:195 to 590 minutes), the intraoperative blood loss was 100.0 (150.0) ml (range:20 to 1 000 ml), the intraoperative blood transfusion rate was 20.1% (6/29), the number of lymph nodes dissected was 10.0 (7.0) pieces (range: 6 to 18 pieces), the first postoperative deflatus time was 3.0 (1.0) days (range:2 to 4 days), The oral feeding time was 5.0 (1.0) days (range: 4 to 7 days), the drainage tube removal time was 8.0 (2.0) days (range: 6 to 26 days), and the postoperative hospital stay time was 10.0 (6.0) days (range:7 to 27 days). The incidence of complications above grade Ⅱ of the Clavien-Dindo complication grading system was 24.1% (7/29), including 3 cases of gastrointestinal bleeding with recurrent high fever, 1 case of delayed gastric emptying, 1 case of bile leakage, and 5 cases of hypoalbuminemia. The total bilirubin was 42.8 (66.8) μmol/L (range:6.8 to 195.9 μmol/L), direct bilirubin was 28.1 (38.5) μmol/L (range:4.3 to 88.6 μmol/L), ALT was 55.8 (56.0) U/L (range:9.9 to 207.1 U/L), AST was 33.9 (17.9) U/L (range:10.6 to 122.7 U/L), and albumin was (32.1±3.8) g/L (range:22.8 to 37.7 g/L), the levels of transaminase and bilirubin in the postoperative liver function indexes were significantly improved compared with those before operation, and the differences were statistically significant (all P<0.05). The mortality rate of patients without perioperative death was 3.4% (1/29) at 90 days after surgery. The results of Cox multivariate regression analysis showed that R0 resection was an independent prognostic factor for survival at 1 year after surgery ( P<0.05). The follow-up time was 15.0 (12.0) months (range:6 to 30 months), 1 of the 29 patients died of intra-abdominal infection 1 week after discharge, and the remaining 28 patients were completely followed up, of which 20 patients had no recurrence and metastasis during the follow-up period, and the tumor-free survival was 15.0 (12.0) months (range:6 to 30 months), the tumor-free survival rate was 65.5% (19/29), the overall survival rate was 68.9% (20/29), and 8 patients with postoperative recurrence and metastasis. One patient with liver metastasis survived after reoperation, and one patient underwent postoperative chemoradiotherapy and died due to recurrence. There were 8 deaths during the follow-up, of which 7 died due to tumor recurrence and metastasis, and 1 died due to previous underlying diseases. Conclusion:Robot-assisted radical resection for hilar cholangiocarcinoma is feasible and effective.
8.Construction of risk prediction model of heart failure in patients with coronary heart disease based on LASSO regression
Yikang XU ; Jingru MA ; Yang YANG ; Lei LIU ; Zhifeng ZHANG ; Siqi SUN ; Manman LI ; Kaiwen ZHAN
China Modern Doctor 2024;62(28):1-5,46
Objective To analyze the risk factors of heart failure in patients with coronary heart disease(CHD),and to construct and verify a nomogram prediction model for the risk of heart failure in patients with CHD.Methods The clinical data of 453 patients with CHD who were hospitalized in the Second Affiliated Hospital of Shenyang Medical College from January to December 2022 were retrospectively analyzed,including 278 patients with CHD combined with heart failure and 175 patients without heart failure.The patients were divided into training group(318 cases)and validation group(135 cases)according to the ratio of 7:3.R software was applied to perform LASSO regression to screen the risk factors,and Logistic regression to establish a prediction model and construct a nomogram.The calibration curve and receiver operating characteristic(ROC)curve were used to evaluate the calibration and discrimination of the model.Results LASSO regression analysis ultimately screened five risk factors from 22 variables,and Logistic regression results showed that age,smoking,history of myocardial infarction,New York Heart Association(NYHA)cardiac function class Ⅳ,and left ventricular ejection fraction(LVEF)were all independent risk factors for heart failure in CHD patients(P<0.05).The model formula was Z=-2.927+0.045 × age+0.886 × smoking+0.808 × history of myocardial infarction-2.829 × NYHA cardiac function class Ⅳ+0.037×LVFF.Internal validation of the model showed that area under the curve was 0.727(95%CI:0.588-0.752),the sensitivity was 40.4%,the specificity was 84.3%,and the Youden index was 0.247.According to the calibration curve,the predicted value of the calibration curve was highly consistent with the actual value,and the Brier score was 0.106.Conclusion The risk prediction model for heart failure in patients with CHD based on LASSO regression has good discrimination and prediction efficiency,which can be used as an evaluation tool for medical staff to predict the risk of patients.
9.Clinicopathological features and prognostic analysis of synchronous mucinous metaplasia and neoplasia of the female genital tract
Linghui LU ; Yiqing CHEN ; Jing LI ; Siqi SHAO ; Fenghua MA ; Yan NING ; Yue SHI ; Chao WANG
Chinese Journal of Oncology 2024;46(12):1195-1208
Objective:Synchronous mucinous metaplasia and neoplasia of the female genital tract (SMMN-FGT) occurring at multiple sites during the same period of time is extremely rare, and the aim of this study was to investigate the clinicopathologic features of SMMN-FGT and its relationship with prognosis.Methods:We retrospectively analyzed the clinicopathological features and follow-up records of 25 cases of SMMN-FGT diagnosed from January 2012 to October 2022 in the case database of Obstetrics and Gynecology Hospital of Fudan University.Results:The median age at onset was 46 years old, respectively. Clinical manifestations included irregular vaginal bleeding or drainage, pelvic pain, and ovarian cysts, etc. Germline genetic test confirmed Peutz-Jeghers syndrome (P-J syndrome) in two patients. All patients underwent surgery, and 13 patients had postoperative adjuvant radiotherapy and/or chemotherapy. The most frequent site of lesion was the cervix (21 cases), with 11, 10 and 16 cases occurring in the endometrium, fallopian tubes and ovaries, respectively. Six cases involved three sites simultaneously, and only one case had all four sites involved at the same time. Among the 9 cases with P53 mutation phenotype, 6 cases had gastric-type mucinous adenocarcinoma, 2 cases had lobular endocervical glandular hyperplasia, and 1 case had mucinous adenocarcinoma, whereas all the minimally deviated adenocarcinomas had wild phenotype of P53. The median follow-up time was 59 months, during which 3 cases died and 6 cases developed local recurrence or distant metastasis. According to our analysis, postoperative recurrence or metastasis was correlated with the FIGO stage of the disease, the number of lesion sites and the severe degree of the uterine lesions ( P<0.05). Conclusions:SMMN-FGT has a relatively good clinical prognosis, and even advanced patients can benefit from surgery and adjuvant therapy. In young patients, the ovaries may be preserved if no evidence of lesions are seen after adequate evaluation. In SMMN-FGT, gastric-type mucinous adenocarcinoma occurring in the cervix may have a better prognosis than gastric-type mucinous adenocarcinoma of the cervix alone, so the accurate diagnosis of SMMN-FGT is critical for clinical management.
10.Effect of Longmu Piyan Prescription on Oxidative Stress in Atopic Dermatitis Mice
Mengxi MA ; Siqi WU ; Qingying WANG ; Yaqin LI ; Jinhe WANG ; Na LANG ; Jianxun REN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):88-95
ObjectiveThis study observes the intervention effect of Longmu Piyan prescription on oxidative stress in BALB/c mice with atopic dermatitis (AD) induced by 2,4-dinitrochlorobenzene (DNCB) and explores its mechanism. MethodThe AD model was established using the method of DNCB sensitization on the back skin of BALB/c mice. Forty male BALB/c mice were randomly divided into a blank group, a model group, a vitamin C control group (0.5×10-3 mg·kg-1), and a Longmu Piyan prescription group (26 g·kg-1). Except for the blank group, other groups were sensitized with different concentrations of DNCB on the back to induce AD, and the blank group was treated with matrix coating. The gastric administration was started on the seventh day after sensitization with 2% DNCB and on the 24th day after sensitization with 0.2% DNCB continuously for 21 days. The changes in skin lesions of each group were directly observed after the experiment. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of interleukin (IL)-4, tumor necrosis factor (TNF)-α, immunoglobulin E (IgE), and reactive oxygen species (ROS) in the serum of each group. The total antioxidant capacity determination kit-trace method (ABTS method) was used to measure the level of total antioxidant capacity (TAOC) in serum. The Hematoxylin eosin (HE) staining method was used to observe the pathological and morphological changes of the skin lesion site. The immunohistochemical method was used to detect the expression of thymic stromal lymphopoietin (TSLP) in the skin lesion site. Western blot was used to detect the expression of filaggrin (FLG) in the dorsal skin lesions. ResultThe results showed that compared with the blank group, the skin lesion score of the model group mice was significantly increased (P<0.01), and HE staining showed characteristic pathological changes of AD in the skin lesion site. At the same time, the expression of TSLP in the skin lesion was significantly increased, and that of FLG was reduced (P<0.05). The levels of TNF-α, IL-4, IgE, and ROS in serum increased, while the activity of TAOC decreased (P<0.01). Compared with the model group, the Longmu Piyan prescription group showed a significant decrease in skin lesion scores and a significant improvement in skin lesion pathology. At the same time, the expression of TSLP decreased, and the expression of FLG increased in the skin lesions (P<0.05). In addition, compared with the model group, the serum levels of TNF-α, IL-4, IgE, and ROS also decreased to varying degrees (P<0.05,P<0.01), and TAOC activity increased in the Longmu Piyan prescription group (P<0.01). ConclusionThere is a significant correlation among the degree of oxidative stress, the severity of skin lesions in AD, and the levels of inflammatory cytokines. Longmu Piyandu prescription can improve AD-like skin lesions in BALB/c mice by promoting ROS clearance, enhancing TAOC, and inhibiting oxidative stress, thus protecting the skin barrier and reducing inflammation.


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