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Objective:To prepare nanoprobes by using polydopamine (PDA) as a carrier which is modified with the sonosensitizer protoporphyrin Ⅸ (PpⅨ) and labeled with 131I, 99Tc m or 177Lu, and to explore the value of these new nanoprobes in diagnosis and combination therapy of breast cancer. Methods:PDA particles were synthesized by aqueous oxidation, and a layer of polyethylene glycol (PEG) and PpⅨ were modified on the surface to product PDA-PEG-PpⅨ. Then the nuclides 131I, 99Tc m and 177Lu were labeled on PDA, respectively, and the labeling yield and stability were determined. The cytotoxicity test was conducted by comparing the viabilities of 4T1 tumor cells in free 131I group and 131I-PDA-PEG-PpⅨ group. The 4T1 cells were divided into 7 groups according to different treatment methods: PDA-PEG-PpⅨ group, PDA-PEG-PpⅨ+ photothermal therapy (PTT) group, PDA-PEG-PpⅨ+ sonodynamic therapy (SDT) group, 131I-PDA-PEG-PpⅨ+ PTT group, 131I-PDA-PEG-PpⅨ+ SDT group, 131I-PDA-PEG-PpⅨ+ PTT+ SDT group (100 μg/ml PDA-PEG-PpⅨ, 925 kBq/ml 131I), and the control group (DMEM culture medium). The cell viabilities of those groups were compared to evaluate the therapeutic effect. 4T1 tumor bearing mouse models were established, then 99Tc m-PDA-PEG-PpⅨ was injected through the tail vein (29.6 MBq) or intratumorally (14.8 MBq) to perform gamma imaging. The independent-sample t test and one-way analysis of variance were used for data analysis. Results:The PDA particles were uniform in size, with a particle size of (160.0±1.5) nm. They had a good photothermal conversion effect. A characteristic peak consistent with PpⅨ (400 nm) appeared in the UV-Vis absorption spectrum of PDA-PEG-PpIX. In the cytotoxicity test, when the radioactivity was 1.850 or 3.700 or 7.400 MBq/ml, the cell viabilities of free 131I group and 131I-PDA-PEG-PpⅨ group were significantly different ((72.18±6.57)% vs (86.07±5.17)%, (59.31±9.06)% vs (80.85±4.21)%, (42.90±1.30)% vs (72.99±5.73)%; t values: 3.71, 4.82, 11.46, P values: 0.006, 0.001, <0.001). The 131I-PDA-PEG-PpⅨ+ PTT+ SDT combination therapy had a better killing effect on 4T1 tumor cells than the combination of 131I-PDA-PEG-PpⅨ+ PTT and 131I-PDA-PEG-PpⅨ+ SDT (cell viabilities: (10.09±2.50)% vs (16.04±2.63)%, (28.65±4.72)%; F=351.66, P<0.001). In vivo imaging showed that 99Tc m-PDA-PEG-PpⅨ was stable in mouse models and could be effectively enriched in tumors. Conclusions:A multifunctional nanoprobe based on PDA is successfully prepared. The radionuclide labeling method is simple and effective, with a good stability. 131I-PDA-PEG-PpⅨ can kill 4T1 cells efficiently. 99Tc m-PDA-PEG-PpⅨ has an obvious tumor concentration effect in mouse models.
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ObjectiveTo investigate the value of serum protoporphyrin IX (PPIX) measurement in evaluating liver damage in patients with HBV-related chronic liver diseases. MethodsA total of 110 patients who were diagnosed with HBV-related chronic liver diseases in The First Affiliated Hospital of Xi’an Medical University from October 2018 to October 2019 were enrolled as case group ［chronic hepatitis B (CHB) group with 50 patients, liver cirrhosis (LC) group with 40 patients, and hepatocellular carcinoma (HCC) group with 20 patients］, and 40 healthy individuals were enrolled as control group. High-performance liquid chromatography was used to measure serum PPIX. A one-way analysis of variance was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test or the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups; the receiver operating characteristic (ROC) curve was plotted to analyze diagnostic value; a Spearman correlation analysis was also performed to investigate correlation. ResultsThe CHB, HC, and HCC groups had a significantly higher level of PPIX than the control group ［44.29 (25.99-85.36) ng/dl, 72.73 (48.28-90.43) ng/dl, and 91.79 (68.34-121.52) ng/dl vs 15.43 (10.87-20.16) ng/dl, all P＜0.05］, and the patients with decompensated LC had a significant increase in the level of PPIX compared with those with compensated LC ［54.50(29.14~85.65) vs 76.09(53.47~104.37)，Z=-2.176, P＜0.05］. PPIX had a sensitivity of ＞85% and a specificity of ＞60% in the diagnosis of CHB, LC, and HCC. The patients in the latent stage of CHB had a significantly higher level of PPIX than those in the control group (Z=-4.303, P＜0.05). In the patients with LC, PPIX was moderately positively correlated with total bilirubin (TBil) (rs=0.587, P＜0.05) and moderately negatively correlated with albumin (rs=-0.408, P＜0.05); in the patients with HCC, PPIX was moderately positively correlated with TBil (rs=0.470, P＜0.05) and moderately negatively correlated with cholinesterase (rs=-0.459, P＜0.05). ConclusionElevated serum PPIX is an early event of liver damage in patients with HBV-related chronic liver diseases and can thus be used as a sensitive parameter for the early warning and assessment of liver damage.
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Objective:To compare the application value of intracellular free heme concentration (FH) detection and high-risk human papillomavirus (HPV) detection in screening cervical cancer and precancerous lesions.Methods:A total of 238 patients with cervical abnormalities who received FH and HPV detection in Huainan First People's Hospital, China from October 2017 to October 2019 were included in this study. Taking liquid-based ThinPrep cytologic test (TCT) results and pathological biopsy results as gold standard, the diagnostic value of FH detection and TCT detection for cervical cancer and precancerous lesions were compared.Results:TCT results revealed normal/inflammatory diagnosis in 97 patients, and atypical squamous cells of undetermined significance (ASCUS) or higher grade diagnosis in 141 patients. Pathological biopsy results reported cervical intraepithelial neoplasia (CIN) grade II or above in 70 out of the 141 patients. The detection rate of FH detection for CIN grade II or above cervical lesions was 92.86% (65/70) and the detection rate of high-risk HPV detection was 95.71% (67/70). The sensitivity and specificity of FH detection in the screening CIN grade II or above cervical lesions were 82.86% (58/70) and 85.92% (60/70), respectively and they were 94.29% (66/70) and 98.59% (69/70) for high-risk HPV detection. There were significant differences in diagnostic sensitivity and specificity between FH dection and high-risk HPV detection ( χ2 = 4.52, 10.25, both P < 0.05). Conclusion:High-risk HPV detection is of high application value in the diagnosis of cervical cancer and precancerous lesions. It has higher sensitivty and specificity in screening cervical cancer and precancerous lesions than FH detection. But FH detection is simpler, more economical and easier to use and is more suitable for large-scale screening of cervical cancer and precancerous lesions than high-risk HPV detection.
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Objective To evaluate the effect of pretreatment with calcipotriol on protoporphyrin Ⅸ (PpIX) content in the normal epithelium of nude mice after topical application of aminolevulinic acid (ALA).Methods A total of 36 BALB/C nude mice were randomly and equally divided into 2 groups:calcipotriol + ALA group topically pretreated with calcipotriol ointment for 3 days followed by topical application of ALA,and ALA group topically treated with ALA alone.At 2,3,4,5,6 and 7 hours after ALA application,3 mice in each group were sacrificed separately,and skin tissues were obtained from the experimental region in the back of mice.A fluorospectrophotometer was used to detect the PpIX content in the normal epithelial tissue of the nude mice,and an inverted fluorescence phase-contrast microscope to observe the fluorescence intensity and distribution of PpIX in the frozen sections of epithelial tissues.Results During 2-8 hours after topical application of ALA,the content of PpIX in the skin tissues of nude mice in the two groups gradually increased over time.Correlation analysis revealed no correlations between the PpIX content in the ALA group and the treatment duration (r =0.451,P =0.369),while the PpIX content in the calcipotriol + ALA group was strongly correlated with the treatment duration (r =0.913,P =0.011).The PpIX content in the ALA group reached a peak at 5 hours [(461.24 ± 43.45) ng/g tissues],while the PpIX content in the calcipotriol + ALA group peaked at 6 hours [(668.88 ± 42.46) ng/g tissues].At 2,3,4,5,6 and 7 hours after ALA application,the PpIX content was significantly higher in the calcipotriol + ALA group than in the ALA group (P ＜ 0.05 or 0.01).Frozen-section examination showed that PpIX was diffusely distributed in the epidermis and dermis of the nude mice,and the fluorescence intensity of PpIX was higher in the calcipotriol + ALA group than in the ALA group at 5,6 and 7 hours after ALA application.Conclusion Pretreatment with calcipotriol can increase the content of PpIX in the normal epidermis and dermis of nude mice after topical application of ALA,which provides a theoretical basis for the clinical application of calcipotriol as a local synergist of ALA-PDT.
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Objective To evaluate the consistency of hemoglobin (Hb) as an diagnostic index for iron deficiency anemia (IDA) in pregnant women with serum ferritin (SF) and free erythrocyte protoporphyrin (FEP).Methods Hb,SF and FEP were assayed for 506 pregnant women with various gestational weeks for the diagnosis of IDA with Hb