1.Preoperative prediction tertiary lymphoid structures of hepatocellular carcinoma on gadoxetate disodium-enhanced MRI
Lin CHEN ; Yiman LI ; Jie CHENG ; Fengxi CHEN ; Ping CAI ; Wei CHEN ; Qingrui LI ; Huarong ZHANG ; Xiaoming LI
Chinese Journal of Radiology 2025;59(6):674-680
Objective:To evaluate the efficacy of gadolinium ethoxybenzyl- diethy-lenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced MRI features in the preoperative prediction of tertiary lymphoid structures (TLS) within hepatocellular carcinoma (HCC) lesions.Methods:This retrospective cross-sectional study included clinical and pathological data from 297 HCC patients treated at the Southwest Hospital, Army Medical University between June 2021 and November 2022. Based on postoperative pathology, patients were categorized into TLS-negative ( n=93) and TLS-positive ( n=204) groups. MRI features of HCC lesions using Gd-EOB-DTPA enhancement and relevant clinical data were analyzed. Intergroup comparisons of imaging features and laboratory findings were performed using independent sample t-test, Mann-Whitney U test, χ2 test, or Fisher exact test, as appropriate. The logistic regression analysis was conducted to identify independent predictors of TLS positivity. A predictive model was constructed and visualized using a nomogram. The model′s predictive performance and clinical utility were assessed using the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The area under the ROC curve (AUC) was compared using the DeLong test. Results:Significant differences were observed between the TLS-negative and TLS-positive groups in alpha-fetoprotein (AFP) levels, intratumoral hemorrhage, and peritumoral satellite nodules in the hepatobiliary phase ( P<0.05). Multivariate logistic regression identified intratumoral hemorrhage ( OR=0.123, 95% CI 0.070-0.216, P<0.001) and peritumoral satellite nodules in the hepatobiliary phase ( OR=0.236, 95% CI 0.093-0.596, P=0.002) as independent predictive factors for TLS-positivity. The imaging model based on these two features yielded an AUC of 0.764 (95% CI 0.709-0.809) for predicting TLS-positivity. When combined with AFP levels, the resulting clinical-imaging model achieved a superior AUC of 0.784 (95% CI 0.732-0.829), which was significantly higher than that of the imaging model alone ( Z=2.20, P=0.028). A nomogram was constructed based on the clinical-imaging model. The calibration curve demonstrated good predictive performance of the nomogram, and the DCA showed that the curve remained above the default line across a range of reasonable threshold probabilities, indicating that patients could derive clinical benefit. Conclusion:A nomogram model based on Gd-EOB-DTPA enhanced MRI features combined with AFP levels can effectively predict the presence of TLS in HCC.
2.Preoperative prediction tertiary lymphoid structures of hepatocellular carcinoma on gadoxetate disodium-enhanced MRI
Lin CHEN ; Yiman LI ; Jie CHENG ; Fengxi CHEN ; Ping CAI ; Wei CHEN ; Qingrui LI ; Huarong ZHANG ; Xiaoming LI
Chinese Journal of Radiology 2025;59(6):674-680
Objective:To evaluate the efficacy of gadolinium ethoxybenzyl- diethy-lenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced MRI features in the preoperative prediction of tertiary lymphoid structures (TLS) within hepatocellular carcinoma (HCC) lesions.Methods:This retrospective cross-sectional study included clinical and pathological data from 297 HCC patients treated at the Southwest Hospital, Army Medical University between June 2021 and November 2022. Based on postoperative pathology, patients were categorized into TLS-negative ( n=93) and TLS-positive ( n=204) groups. MRI features of HCC lesions using Gd-EOB-DTPA enhancement and relevant clinical data were analyzed. Intergroup comparisons of imaging features and laboratory findings were performed using independent sample t-test, Mann-Whitney U test, χ2 test, or Fisher exact test, as appropriate. The logistic regression analysis was conducted to identify independent predictors of TLS positivity. A predictive model was constructed and visualized using a nomogram. The model′s predictive performance and clinical utility were assessed using the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The area under the ROC curve (AUC) was compared using the DeLong test. Results:Significant differences were observed between the TLS-negative and TLS-positive groups in alpha-fetoprotein (AFP) levels, intratumoral hemorrhage, and peritumoral satellite nodules in the hepatobiliary phase ( P<0.05). Multivariate logistic regression identified intratumoral hemorrhage ( OR=0.123, 95% CI 0.070-0.216, P<0.001) and peritumoral satellite nodules in the hepatobiliary phase ( OR=0.236, 95% CI 0.093-0.596, P=0.002) as independent predictive factors for TLS-positivity. The imaging model based on these two features yielded an AUC of 0.764 (95% CI 0.709-0.809) for predicting TLS-positivity. When combined with AFP levels, the resulting clinical-imaging model achieved a superior AUC of 0.784 (95% CI 0.732-0.829), which was significantly higher than that of the imaging model alone ( Z=2.20, P=0.028). A nomogram was constructed based on the clinical-imaging model. The calibration curve demonstrated good predictive performance of the nomogram, and the DCA showed that the curve remained above the default line across a range of reasonable threshold probabilities, indicating that patients could derive clinical benefit. Conclusion:A nomogram model based on Gd-EOB-DTPA enhanced MRI features combined with AFP levels can effectively predict the presence of TLS in HCC.
3.Clinical value of preoperative Gd-EOB-DTPA-enhanced magnetic resonance imaging in predic-ting microvascular invasion and intratumoral tertiary lymphoid structures in hepatocellular carcinoma
Yiman LI ; Jie CHENG ; Fengxi CHEN ; Lin CHEN ; Ping CAI ; Wei CHEN ; Mi PEI ; Guojiao ZUO ; Qingrui LI ; Xi LIU ; Huarong ZHANG ; Xiaoming LI ; Xiaoping LUO
Chinese Journal of Digestive Surgery 2024;23(12):1556-1565
Objective:To investigate the clinical value of preoperative gadolinium ethoxy-benzyldiethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in predicting microvascular invasion (MVI) and intratumoral tertiary lymphoid structures (TLSs) in hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 304 HCC patients who were admitted to The First Affiliated Hospital of Army Medical University and 10 HCC patients who were admitted to The Second Affiliated Hospital of Chongqing Medical University from June 2021 to June 2023 were collected. There were 272 males and 42 females, aged (56±11)years. Using a random number table method, patients were divided into a training set including 220 cases and a validation set including 94 cases in a 7:3 ratio. Among the 314 patients, 106 cases had MVI and TLSs-positive HCC (MT-HCC), and 208 cases had non-MT-HCC. All patients underwent preoperative Gd-EOB-DTPA-enhanced MRI and radical resection. Observation indicators: (1) clinicopathological characteristics of MT-HCC and non-MT-HCC patients; (2) imaging characteristics of MT-HCC and non-MT-HCC patients; (3) imaging features associated with MT-HCC diagnosis; (4) nomogram predictive model construction and evaluation for MT-HCC. Comparison of measurement data with normal distribution between groups was analyzed using the t test. Comparison of measurement data with skewed distribution between groups was analyzed using the nonpara-meter rank sum test. Univariate analysis was conducted using the corresponding statistical methods based on data type. Multivariate analysis was conducted using the logistic regression model. A nomo-gram predictive model was constructed based on results of multivariate analysis, and receiver operating characteristic (ROC) curves were plotted to evaluate the model's performance with the area under curve (AUC). Calibration curve and decision curve analyses were used to assess the calibration and clinical validity of nomogram predictive model. Results:(1) Clinicopathological characteristics of MT-HCC and non-MT-HCC patients. In the training set, there were significant differences between MT-HCC and non-MT-HCC patients in terms of age, white blood cell count, and alpha fetoprotein level ( t=2.488, Z=-2.515, χ2=4.014, P<0.05). (2) Imaging characteristics of MT-HCC and non-MT-HCC patients. In the training set, there were significant differences in tumor morphology, intratumoral hemorrhage, peritumoral abnormal enhancement in arterial phase, capsule presence, intratumoral necrosis or ischemia >20%, intratumoral necrosis or ischemia >50%, peritumoral hypointensity in the hepatobiliary phase, intravascular tumor thrombus, arterial phase rim-like hyperenhancement, and mosaic architecture between MT-HCC and non-MT-HCC patients ( χ2=8.811, 5.586, 13.962, 31.616, 10.154, 4.835, 5.111, 14.425, 7.112, 5.526, P<0.05). (3) Imaging features associated with MT-HCC diagnosis. Results of multivariate analysis identified the absence of intratumoral hemorrhage, incom-plete capsule, and mosaic architecture as independent risk factors for diagnosing MT-HCC ( hazard ratio=3.846, 7.827, 2.345, P<0.05). (4) Nomogram predictive model construction and evaluation for MT-HCC. A nomogram predictive model for MT-HCC was constructed based on the independent risk factors (absence of intratumoral hemorrhage, incomplete capsule, and mosaic architecture) iden-tified in the multivariate analysis. The ROC curve analysis showed that AUC of nomogram predictive model was 0.778 (95% confidence interval as 0.714-0.843), with sensitivity and specificity of 0.857 and 0.573 in the training set. In the validation set, the area under the curve, sensitivity, and specifi-city were 0.825 (95% confidence interval as 0.745-0.926), 0.655, and 0.877, respectively. The calibra-tion curves for both the training set and the validation set closely aligned with the standard curve, indicating high calibration accuracy. The decision curve analysis demonstrated net clinical benefits at thresholds of 0.130-0.690 in the training set and 0.060-0.750 in the validation set. Conclusions:The absence of intratumoral hemorrhage, incomplete capsule, and mosaic architecture are independent risk factors for diagnosing MT-HCC. A nomogram model based on imaging features can predict MT-HCC in HCC patients.
4.Clinical value of preoperative Gd-EOB-DTPA-enhanced magnetic resonance imaging in predic-ting microvascular invasion and intratumoral tertiary lymphoid structures in hepatocellular carcinoma
Yiman LI ; Jie CHENG ; Fengxi CHEN ; Lin CHEN ; Ping CAI ; Wei CHEN ; Mi PEI ; Guojiao ZUO ; Qingrui LI ; Xi LIU ; Huarong ZHANG ; Xiaoming LI ; Xiaoping LUO
Chinese Journal of Digestive Surgery 2024;23(12):1556-1565
Objective:To investigate the clinical value of preoperative gadolinium ethoxy-benzyldiethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in predicting microvascular invasion (MVI) and intratumoral tertiary lymphoid structures (TLSs) in hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 304 HCC patients who were admitted to The First Affiliated Hospital of Army Medical University and 10 HCC patients who were admitted to The Second Affiliated Hospital of Chongqing Medical University from June 2021 to June 2023 were collected. There were 272 males and 42 females, aged (56±11)years. Using a random number table method, patients were divided into a training set including 220 cases and a validation set including 94 cases in a 7:3 ratio. Among the 314 patients, 106 cases had MVI and TLSs-positive HCC (MT-HCC), and 208 cases had non-MT-HCC. All patients underwent preoperative Gd-EOB-DTPA-enhanced MRI and radical resection. Observation indicators: (1) clinicopathological characteristics of MT-HCC and non-MT-HCC patients; (2) imaging characteristics of MT-HCC and non-MT-HCC patients; (3) imaging features associated with MT-HCC diagnosis; (4) nomogram predictive model construction and evaluation for MT-HCC. Comparison of measurement data with normal distribution between groups was analyzed using the t test. Comparison of measurement data with skewed distribution between groups was analyzed using the nonpara-meter rank sum test. Univariate analysis was conducted using the corresponding statistical methods based on data type. Multivariate analysis was conducted using the logistic regression model. A nomo-gram predictive model was constructed based on results of multivariate analysis, and receiver operating characteristic (ROC) curves were plotted to evaluate the model's performance with the area under curve (AUC). Calibration curve and decision curve analyses were used to assess the calibration and clinical validity of nomogram predictive model. Results:(1) Clinicopathological characteristics of MT-HCC and non-MT-HCC patients. In the training set, there were significant differences between MT-HCC and non-MT-HCC patients in terms of age, white blood cell count, and alpha fetoprotein level ( t=2.488, Z=-2.515, χ2=4.014, P<0.05). (2) Imaging characteristics of MT-HCC and non-MT-HCC patients. In the training set, there were significant differences in tumor morphology, intratumoral hemorrhage, peritumoral abnormal enhancement in arterial phase, capsule presence, intratumoral necrosis or ischemia >20%, intratumoral necrosis or ischemia >50%, peritumoral hypointensity in the hepatobiliary phase, intravascular tumor thrombus, arterial phase rim-like hyperenhancement, and mosaic architecture between MT-HCC and non-MT-HCC patients ( χ2=8.811, 5.586, 13.962, 31.616, 10.154, 4.835, 5.111, 14.425, 7.112, 5.526, P<0.05). (3) Imaging features associated with MT-HCC diagnosis. Results of multivariate analysis identified the absence of intratumoral hemorrhage, incom-plete capsule, and mosaic architecture as independent risk factors for diagnosing MT-HCC ( hazard ratio=3.846, 7.827, 2.345, P<0.05). (4) Nomogram predictive model construction and evaluation for MT-HCC. A nomogram predictive model for MT-HCC was constructed based on the independent risk factors (absence of intratumoral hemorrhage, incomplete capsule, and mosaic architecture) iden-tified in the multivariate analysis. The ROC curve analysis showed that AUC of nomogram predictive model was 0.778 (95% confidence interval as 0.714-0.843), with sensitivity and specificity of 0.857 and 0.573 in the training set. In the validation set, the area under the curve, sensitivity, and specifi-city were 0.825 (95% confidence interval as 0.745-0.926), 0.655, and 0.877, respectively. The calibra-tion curves for both the training set and the validation set closely aligned with the standard curve, indicating high calibration accuracy. The decision curve analysis demonstrated net clinical benefits at thresholds of 0.130-0.690 in the training set and 0.060-0.750 in the validation set. Conclusions:The absence of intratumoral hemorrhage, incomplete capsule, and mosaic architecture are independent risk factors for diagnosing MT-HCC. A nomogram model based on imaging features can predict MT-HCC in HCC patients.
5.Clinical value of gadolinium ethoxybenzyl diethylanetriaminepentaacetic acid enhanced MRI in the preoperative diagnosis of macrotrabecular-massive hepatocellular carcinoma
Xiaoming LI ; Ping CAI ; Lin CHENG ; Chen LIU ; Huarong ZHANG ; Shiguang LI
Chinese Journal of Digestive Surgery 2021;20(11):1218-1226
Objective:To investigate the clinical value of gadolinium ethoxybenzyl diethy-lanetriaminepentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) in the preoperative diagnosis of macrotrabecular-massive hepatocellular carcinoma (MTM-HCC).Methods:The diagnostic test was conducted. The clinicopathological data of 150 HCC patients who were admitted to the First Affiliated Hospital of Army Medical University from January 2019 to December 2020 were collected. There were 116 males and 34 females, aged (53±10)years. There were 38 MTM-HCC patients and 112 non-macrotrabecular-massive hepatocellular carcinoma (nMTM-HCC) patients. All patients received Gd-EOB-DTPA enhanced MRI examination. Observation indicators: (1) clinicopathological features of MTM-HCC and nMTM-HCC; (2) imaging features of MTM-HCC and nMTM-HCC; (3) imaging features for diagnosis of MTM-HCC. The normality test of continuous data was analyzed by the Kolmogorov-Smirnov test. Measurement data with normal distribution and homoscedasticity were represented as Mean± SD, and comparison between groups was analyzed using the independent sample t test. Measurement data with skewed distribution were represented as M( P25, P75), and comparison between groups was analyzed using Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. Multivariate analysis was conducted using the Logistic regression model. The receiver operating characteristic (ROC) curve was used to evaluate diagnostic value of indicators, and Delong test was used for comparison. Results:(1) Clinicopathological features of MTM-HCC and nMTM-HCC: the alpha-fetoprotein and cases with microvascular invasion were 329 μg/L(20 μg/L,1 034 μg/L) and 24 for MTM-HCC patients, versus 25 μg/L(8 μg/L,200 μg/L) and 31 for nMTM-HCC patients, showing significant differences between the two groups ( Z=-3.306, χ2=15.380, P<0.05). (2) Imaging features of MTM-HCC and nMTM-HCC: cases with regular morphology of tumor, intra-tumoral fat, arterial phase peritumoral enhancement, complete capsule, intratumoral necrosis or ischemia, peritumoral hypointense at hepatobiliary phase (HBP) were 6, 4, 20, 5, 28, 17 for MTM-HCC patients, versus 44, 40, 21, 43, 26, 11 for nMTM-HCC patients, showing significant differences between the two groups ( χ2=7.049, 8.684, 16.399, 8.303, 31.368, 22.783, P<0.05). (3) Imaging features for diagnosis of MTM-HCC. ① Results of multivariate analysis showed that intratumoral fat, intratumoral necrosis or ischemia were independent predictors for MTM-HCC ( hazard ratio=4.033,0.215, 95% confidence interval as 1.196-13.603, 0.079-0.588, P<0.05). ② Diagnostic efficacy: the arear under ROC curve, sensitivity and specificity of intratumoral fat combined with intratumoral necrosis or ischemia for diagnosis of MTM-HCC were 0.799(95% confidence interval as 0.718-0.880, P<0.05), 73.7%, 76.8%. The above indicators of intratumoral fat for diagnosis of MTM-HCC were 0.626(95% confidence interval as 0.530-0.721, P<0.05), 89.5%, 35.7%. The above indicators of intratumoral necrosis or ischemia for diagnosis of MTM-HCC were 0.752(95% confidence interval as 0.659-0.845, P<0.05), 73.7%, 76.8%. There were significant differences in the diagnostic efficacy between the intratumoral fat combined with intratumoral necrosis or ischemia and single intratumoral fat, between the intratumoral fat combined with intratumoral necrosis or ischemia and single intratumoral necrosis or ischemia, respectively ( P<0.05). Conclusions:Intratumoral fat, intratumoral necrosis or ischemia on Gd-EOB-DTPA MRI are independent predictors for MTM-HCC. The two combined features has higher diagnostic efficacy. Gd-EOB-DTPA MRI can be used for pre-operative diagnosis of MTM-HCC.
6.Effect and mechanism of lncRNA UCA1 target regulating miR-185-5p on non-small cell lung cancerA549 cell
CAI Huarong ; WANG Zhiqiang ; JIANG Yuequan
Chinese Journal of Cancer Biotherapy 2018;25(6):555-561
Objective: To investigate the effect and underlying mechanism of Long non-coding RNAurothelial carcinoma associated 1 (lncRNA UCA1) on proliferation, invasion and migration of non-small cell lung cancer (NSCLC) A549 cells. Methods: NSCLS A549 cells were cultured and transfected with lentivirus; RT-PCR was employed to detect the levels of UCA1 in A549 cells. The relationship between UCA1 and miR-185-5p was validated by luciferase reporter assays. Cell viability ofA549 cells was measured by MTT. Cell invasion and migration were determined by Transwell and Wound healing assay, respectively; and western blotting was performed for measuring the levels of Wnt1/β-catenin pathway-related proteins. Results: sh-UCA1 significantly decreased UCA1 expression and increased miR-185-5p expression in A549 cells (all P<0.05). miR-185 inhibitor attenuated the promotion effect of sh-UCA1 on miR-1855p (P<0.05). UCA1 could significantly down-regulate miR-185-5p expression in A549 cells (P<0.05), which was reversed by miR-185 mimic (P<0.05). Luciferase reporter assay validated the binding site on UCA1 to link miR-185-5p. sh-UCA1 significantly inhibited cell proliferation, invasion and migration ofA549 cells (all P<0.05), and also decreased the protein levels of Wnt1, β-catenin and TCF-4 notably (all P<0.05); however, miR-185 inhibitor attenuated such inhibitory effects of sh-UCA1 (P<0.05). Conclusion: UCA1 could promote proliferation, invasion and migration of A549 cells through targeting miR-185-5p, and the mechanisms might be related with activation of Wnt1/β-catenin pathway.
7.Prognostic analysis of 313 aged pancreatic cancer patients in hospital treatment between Uygur and Han nationality in Xinjiang area
Lei PEI ; Ceng CAI ; Rui MAO ; Huarong ZHAO ; Hua ZHANG ; Yongxing BAO
Practical Oncology Journal 2016;30(1):1-6
Objective To investigate the prognostic factors of survival time of the Uygur and Han nation-ality elderly patients( over 60 years) with pancreatic cancer in Xinjiang.Methods We carried on a retrospective study of 313 aged patients diagnosed with pancreatic cancer in The First Affiliated Hospital of Xinjiang Medical University from January 1st,2003 to May 30th,2015.We used Kpalan-Meier method for calculation of survival, used Log-rank method for those factors which could affect the prognosis of patients,at last we used Cox propor-tional risk model for those multiple factors which match the role.Results Three hundred and thirteen cases with pancreatic cancer had a median survival of 157 days,and survival rates of half a year,1 and 2 year were 34.8%, 18.5%,7.0%.There was a statistic difference between Uygur patients′and Han patients′survival time(P<0.05).Single factor analysis showed the nationality,tumor size,surgery,ZPS(ECOG),Clinical stage(TNM), chemotherapy and radiotherapy,carcino-embryonic antigen(CEA)level and cancer antigen 199(CA199)level before treatment with outcome(P<0.05).Multiple factor analysis showed that the clinical stage,surgery(P<0.05)can be regarded as independent prognostic decision factors.Conclusion The clinical staging,surgical treatment could be regarded as independent prognostic factors for the elderly prognosis of pancreatic cancer.Both of the Han and Uygur patients,earlier discovered and more appropriate surgery treatment are the key for the elder-ly patients with pancreatic cancer.
8.Expression and significance of Notch1 and Bmi-1 protein in lung cancer tissue
Chinese Journal of Tissue Engineering Research 2016;20(5):683-687
BACKGROUND:Studies have found that Notch pathway and Bmi-1 gene both have the ability to regulate stem cel self-renew. Functional dysfunction of the both may have a great relationship with tumorigenesis. OBJECTIVE:To investigate the expression and clinical significance of Notch1 and Bmi-1 protein in lung tissue. METHODS:Eighty-seven lung cancer tissue samples (lung cancer group) and forty pathologicaly confirmed normal lung tissue samples (normal group) were obtained from related surgeries and included as research objects. The protein expression of Notch1 and Bmi-1 in specimens of these two groups was measured by immunohistochemistry SP method. The relationship between Notch1 and Bmi-1 protein expression and clinicopathological features of lung cancer patients was analyzed. RESULTS AND CONCLUSION: The positive rate of Notch1, Bmi-1 protein expression was respectively 61% and 47%, which was significantly higher in the lung cancer group than that in the normal group (P < 0.05). In the lung cancer group, Notch1 protein expression was significantly positively correlated with Bmi-1 protein expression (r=0.567,P < 0.001). There were no significant differences in Notch1 and Bmi-1 protein expression rates between different genders and different pathological types of patients (P < 0.05). The Notch1 and Bmi-1 protein positive expression rates in poorly-differentiated, TNM stage III-IV lung cancer patients with lymph node metastasis were significantly higher than those in wel- and moderately-differentiated, TNM stage I-II lung cancer patients without lymph node metastasis (P < 0.05). These results demonstrate that Notch1 and Bmi-1 protein may have certain relationship with the occurrence and development of lung cancer.
9.Construction of RGD-TAT modified liposomes and evaluation of its targeting on glioma
Jichun HUANG ; Huarong CAI ; Yuequan JIANG
Chinese Journal of Biochemical Pharmaceutics 2014;(3):1-3
Objective To construct RGD-TAT modified liposomes(RGD-TAT-LPs)and evaluate its glioma targeting efficiency.Methods RGD-TAT-LPs was constructed by film-ultrasonic method,its appearance,particle size and Zeta potential were mearsured. Cellular uptake of LPs,TAT-LPs, RGD-LPs and RGD-TAT-LPs was used to evaluate the affinity to C6 cells.C6 cells were xenografted in athymic mice to establish the animal model,which were used to evaluate the distribution of liposomes in vivo. Results The particle diameter of RGD-TAT-LPs was (1 16.5 ±1 1.3 )nm,and its Zeta potential was (23.2 ±3.5 )mV. Cellular uptake experiments demonstrated the cell uptake efficiency of RGD-TAT-LPs by C6 cells were 2.9-fold,2.3-fold and 4.7-fold than that of RGD-LPs,TAT-LPs and LPs respectively. The in vivo imaging showed that RGD-TAT-LPs had the strongest fluorescence intensity in brain. Conclusion The RGD-TAT-LPs might serve as a promising delivery system of antitumor drugs.
10.Influence of kaempferol on TGF-β1/Smads signal path in liver tissue of mice with Schistosoma japonicum infection
Wen CAI ; Lei ZHAO ; Huarong LI ; Shuling ZHANG
Chinese Journal of Schistosomiasis Control 2014;(4):399-404,419
Objective To investigate the influence of kaempferol on transforming growth factor(TGF)-β1/Smads signal trans-duction in liver tissue of mice with schistosomiasis liver fibrosis. Methods Forty BALB/c mice were randomly divided into a normal control group(8 mice),a praziquantel group(8 mice ),and 4 praziquantel+kaempferol groups with different kaempfer-ol dosages(5,10,15,20 mg/kg respectively,6 mice each group). Besides the normal control group,all the mice in the other 5 groups were infected with Schistosoma japonicum. After the infection for 6 weeks,the praziquantel group and the 4 praziquantel+ kaempferol groups were treated with praziquantel 500 mg/(kg · d) for 2 d,then the mice in the praziquantel group were drenched with normal saline for 6 weeks,and those in the 4 praziquantel+kaempferol groups were drenched with kaempferol 5, 10,15,20 mg/kg respectively for 6 weeks. After the treatment,all the animals were sacrificed by the cervical dislocation meth-od,and the area of egg granuloma and the degree of fibrosis in the livers of the mice were observed by HE and Masson staining. The expressions of TGF-β1,Smad2/3,Smad7 proteins were measured by the immunohistochemical method,and the mRNA lev-els of the 3 proteins were detected by RT-PCR. Results Compared with the mice in the praziquantel group,the areas of egg granuloma of the liver of the mice in the 4 praziquantel+kaempferol groups were smaller,and the degrees of the hepatic fibrosis of the mice were lesser,and their expressions of Smad2 and Smad3 at protein and their mRNA levels were significantly lower (all P<0.05),while the expression of Smad7 at protein and its mRNA level were significantly higher(all P<0.05). Conclu-sion By decreasing the expressions of TGF-β1 and Smad2/3,and increasing the expression of Smad7,kaempferol can signifi-cantly reduce the degrees of hepatic fibrosis and granuloma caused by schistosome eggs after the praziquantel treatment.

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