1.Research progress of nano delivery system in breast cancer treatment
Guoqing LI ; Ping JIAO ; Ruifang WANG ; Dujuan ZHANG
China Pharmacy 2023;34(1):122-128
Breast cancer is a malignant tumor that seriously threatens women’s health at present. Although surgical treatment is the most direct and effective, it is limited by many factors and needs to be assisted by other treatments. In addition to conventional radiotherapy, these adjuvant therapies also include chemotherapy, gene therapy, phototherapy and so on. However, the therapeutic agents used in these treatment methods have some limitations, such as poor water-solubility, instability and targeting. With the development of nano-technology, more and more researchers construct and study nano delivery system for breast tumor treatment, such as response system designed based on tumor microenvironment, temperature sensitive response system, nano delivery system based on specific proteins of tumor cell membrane, etc. The author summarizes the nano delivery system, and finds that these nano delivery systems can not only improve the water-solubility and stability of the therapeutic agents, but also accurately deliver them to the breast tumor site by targeted means, improve the efficacy and reduce toxic side effects, which provides new ideas for the treatment of breast cancer in the future.
2.Analysis of risk factors associated with acute Stanford type B aortic dissection complicated with pleural effusion and observation of the curative effect after intracavitary repair
Lingfei ZHENG ; Dujuan MENG ; Yasong WANG ; Tienan ZHOU ; Xiaozeng WANG
Chinese Journal of Internal Medicine 2023;62(8):964-971
Objective:To investigate the risk factors of acute Stanford type B aortic dissection (TBAD) complicated with pleural effusion (PE) and the short-term and long-term outcomes of thoracic endovascular aortic repair (TEVAR).Methods:A case-control study. The clinical and imaging data of 1 083 patients with acute TBAD admitted to the General Hospital of Northern Theater Command from April 2002 to December 2020 were retrospectively analyzed, including 211 cases with pleural effusion and 872 cases without pleural effusion. The baseline analysis of the two groups of patients was performed. The risk factors associated with pleural effusion were analyzed by binary logistic regression, and the results were expressed as odds ratio ( OR) and 95% confidence interval ( CI). According to the quantity of pleural effusion, they were simultaneously divided into small pleural effusion group and medium large pleural effusion group, to compare the short-term and long-term effects of TEVAR patients with different amounts of pleural effusion. Results:The incidence of pericardial effusion (17.5% vs. 3.8%, P<0.001), anemia (21.3% vs. 12.5%, P=0.001), aortic spiral tear (49.8% vs. 37.8%, P=0.002), dissection tear over diaphragm (57.8% vs. 48.1%, P=0.011), serum creatinine [85 (69, 111) vs. 81 (67, 100) μmol/L, P=0.011] and white blood cell levels[(11.3±4.2)×10 9/L vs. (10.3±4.2)×10 9/L, P=0.002] in acute TBAD pleural effusion group were significantly higher than those in non-pleural effusion group, and the hemoglobin level was significantly lower than that in non-pleural effusion group [(128±20) vs. (133±17) g/L, P<0.05]. Logistic stepwise regression analysis showed that pericardial effusion ( OR=5.038,95% CI 2.962-8.568, P<0.001), anemia ( OR=2.047,95% CI 1.361-3.079, P=0.001), spiral tear ( OR=1.551,95% CI 1.030-2.336 , P=0.002) and elevated white blood cell ( OR=1.059,95% CI 1.011-1.102, P=0.005) were independent risk factors for TBAD complicated with pleural effusion. The incidences of all-cause death (4/19 vs. 1.5% vs. 0.9%, P<0.001), aortogenic death (4/19 vs. 0.7% vs. 0.7%, P<0.001) and aortic related adverse events (4/19 vs. 1.5% vs. 1.1%, P<0.001) in patients with large pleural effusion during TEVAR operation were significantly higher than those in patients with small pleural effusion and those without pleural effusion, and the differences were statistically significant. At 1 month follow-up after TEVAR, the incidence of all-cause death (4/16 vs. 3.3% vs. 1.6%, P<0.001), aortogenic death (4/16 vs. 0.8% vs.0.7%, P<0.001), aorta related adverse events (4/16 vs. 4.1% vs. 4.7%, P=0.013) and overall clinical adverse events (4/16 vs.9.8% vs. 6.7%, P=0.014) in the medium and large thoracic group were significantly higher than those in the small pleural effusion group and no pleural effusion group, and the differences were statistically significant. At 1 year follow-up after TEVAR, the incidence of all-cause death (4/15 vs. 4.9% vs. 3.9%, P=0.004), aortogenic death (4/15 vs.2.5% vs. 2.1%, P<0.001), aorta related adverse events (5/15 vs. 11.5% vs. 9.4%, P=0.012) and overall clinical adverse events (5/15 vs. 18.9% vs. 13.1%, P=0.029) in the medium and large thoracic group were significantly higher than those in the small pleural effusion group and no pleural effusion group, and the differences were statistically significant. Conclusions:Single center data showed that pericardial effusion, anemia, spiral tear and elevated white blood cell were independent risk factors for acute TBAD complicated with pleural effusion; the early (1 month) and long-term (1 year) rates of all-cause death, aortic mortality, aortic adverse events and overall clinical adverse events were significantly higher in TBAD patients with moderate pleural effusion after TEVAR, and moderate and large pleural effusion was an independent risk factor for near and long-term aortic related adverse events after TEVAR surgery.
3.Genetic analysis of a Chinese pedigree with Lesch-Nyhan syndrome.
Dujuan WANG ; Jingjing ZHAO ; Juan TENG ; Wen LI ; Xiangyu ZHAO ; Lin LI
Chinese Journal of Medical Genetics 2023;40(6):723-726
OBJECTIVE:
To explore the genetic etiology for a Chinese pedigree affected with Lesch-Nyhan syndrome.
METHODS:
Members of the pedigree who had visited the Genetic Counseling Clinic of Linyi People's Hospital on February 10, 2022 were selected as the study subjects. Clinical data and family history of the proband were collected, and trio-whole exome sequencing (trio-WES) was carried out for the proband and his parents. Candidate variants were verified by Sanger sequencing.
RESULTS:
Trio-WES revealed that both the proband and his cousin brother had harbored a hemizygous c.385-1G>C variant in intron 4 of the HPRT1 gene, which was unreported previously. A heterozygous c.385-1G>C variant of the HPRT1 gene was also found in the proband's mother, grandmother, two aunts, and a female cousin, whilst all phenotypically normal males in his pedigree were found to have a wild type for the locus, which has conformed to an X-linked recessive inheritance.
CONCLUSION
The heterozygous c.385-1G>C variant of the HPRT1 gene probably underlay the Lesch-Nyhan syndrome in this pedigree.
Male
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Humans
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Female
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Lesch-Nyhan Syndrome/genetics*
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Pedigree
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East Asian People
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Heterozygote
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Introns
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Mutation
4.Rapid detection of the bacterial drug susceptibility testing based on AIE technology
Lisha LAI ; Rentang DENG ; Lu ZHANG ; Yubang JIE ; Lingping XIE ; Zhihong HUANG ; Liming YIN ; Dujuan WANG ; Lijuan LI ; Junfa XU ; Lanfen PENG ; Wenjin FU
Chinese Journal of Laboratory Medicine 2023;46(11):1186-1192
Objective:Based on the principle that the aggregation-induced emission (AIE) fluorescent probe 6PD-DPAN could bind and aggregate with bacteria, and the fluorescence intensity could reflect the quantity of bacteria, a new method for rapid, convenient, and accurate bacterial drug sensitivity testing was established, which provided a basis for rapid and accurate clinical drug use.Methods:This was a methodological evaluation study. A total of 107 clinical isolates were collected from Houjie Hospital of Dongguan City from January to December 2022, among which 46 isolates were used for the establishment of the new method, and 61 isolates were used for methodological validation. The minimum inhibitory concentration (MIC) determined by broth microdilution method was used as the gold standard, and three antibacterial drugs, gentamicin, levofloxacin, and cefotaxime, were used as experimental drugs. The AIE plate was incubated for 4 hours, and the fluorescence intensity was measured every half an hour to draw a fluorescence change curve. The MIC results were compared with the CLSI breakpoints to determine the bacteria as sensitive, intermediate, or resistant. To simplify the detection process, the ratio of fluorescence intensity at 4 hours(R) was calculated, and the ROC curve was used to analyze the efficacy of R in determining bacterial growth and establish its cutoff value. The new method was used to determine the MIC of 61 clinical isolates, with broth microdilution method as the gold standard. The basic consistency, categorical consistency, very major errors, and major errors of the new method were analyzed, and the consistency between the two methods was determined by the Kappa test.Results:ROC curve analysis of the R after 4 hours of culture: The cut-off value was 3.0, with both sensitivity and specificity for determining bacterial growth being 100%. The median (interquartile) R for bacterial growth inhibition was 11.1 (8.6, 14.4); the median R-value for bacterial growth was 1.1 (1.0, 1.2). Compared to the gold standard, the newly established method showed 100% (61/61) essential agreement in detecting MICs of 61 clinical isolates, with a categorical agreement of 96.7% (59/61). There were no very major or major errors, and the Kappa value was 0.94, indicating good consistency between the newly established method and the microbroth dilution method.Conclusions:This study successfully established a new method for bacterial drug sensitivity testing based on AIE technology, which could obtain satisfactory results within 5 hours, providing a basis for early precision drug treatment in clinical practice.
5.Predictors of intracranial hemorrhage in patients with cerebral venous sinus thrombosis
Xinchen MA ; Ruijie YANG ; Xiaoqiong DU ; Xuan HE ; Luna WANG ; Dujuan SHA
International Journal of Cerebrovascular Diseases 2022;30(1):27-31
Objective:To investigate the predictors of intracranial hemorrhage in patients with cerebral venous sinus thrombosis (CVST).Methods:Patients with CVST treated in Drum Tower Hospital Affiliated to Medical School of Nanjing University from January 2008 to March 2021 were retrospectively enrolled. The risk factors, clinical manifestations, imaging examination and 90 d follow-up data were collected. The complicated intracranial hemorrhage group and non-intracranial hemorrhage group were compared. Multivariate logistic regression analysis was used to determine the independent predictors of intracranial hemorrhage in patients with CVST. Results:A total of 104 patients with CVST were enrolled, including 42 males and 62 females. Their age was 35.24 ± 10.92 years old (range 22-68 years). Thirty-eight patients (36.84%) were complicated with intracranial hemorrhage, including 34 hemorrhagic cerebral infarction and 4 complicated subarachnoid hemorrhage. Univariate analysis showed that compared with the non-intracerebral hemorrhage group, the intracranial hemorrhage group was more common in puerperal/pregnant patients (60.52% vs. 48.48%; P=0.012), with more acute onset (57.89% vs. 48.48%; P=0.004), focal neurological signs (47.37% vs. 19.70%; P=0.003) and seizure (39.47% vs. 18.18%; P=0.017), and the site of thrombosis was more common in the superior sagittal sinus (57.89% vs. 36.36%; P=0.033). Multivariate logistic regression analysis showed that puerperium/pregnancy (odds ratio 2.857, 95% confidence interval 1.095-7.453; P=0.031) and superior sagittal sinus thrombosis (odds ratio 2.847, 95% confidence interval 1.110-7.302; P=0.027) were the independent predictors of intracranial hemorrhage in patients with CVST. The analysis at 90 d after onset showed that there was no significant difference in the good outcome rate between the intracranial hemorrhage group and the non-intracranial hemorrhage group (86.84% vs. 89.39%; P=0.695). Conclusions:Puerperium/pregnancy and superior sagittalsinus thrombosis are the independent risk factors for intracranial hemorrhage in patients with CVST. However, complicated with intracranial hemorrhage is not associated with 90-day clinical outcomes.
6.Comparison of left and right ventricular Tei indexes in newborns of different gestational age and birth weight
Honglin LEI ; Dujuan XU ; Bo YANG ; Bao JIN ; Li LI ; Yi REN ; Xiaotong SONG ; Leyao WANG ; Xiangyu GAO
Chinese Journal of Neonatology 2022;37(6):488-493
Objective:To compare left and right ventricular Tei indexes and to determine the reference range in newborns of different gestational age (GA) and birth weight (BW).Methods:From February 2019 to June 2021, newborns admitted to the Neonatal Intensive Care Unit of our hospital were enrolled. Tei indexes were measured and calculated during 24 h~7 d after birth and reexamined 1~2 weeks later in some of the newborns. The newborns were assigned into <32 w group, 32~36 w group and ≥ 37 w group according to their GA, < 1 500 g group, 1 500~2 499 g group and ≥2 500 g group according to their BW, and early newborn group (1~7 d) and late newborn group (>7 d) according to their age of evaluation. The data were analyzed using t test, one-way analysis of variance (ANOVA) and correlation analysis with SPSS 20.0 statistical software. Results:A total of 128 cases were included. 42 cases in <32 w group, 43 in 32~36 w group and 43 in ≥37 w group. 42 cases in <1 500 g group, 42 in 1 500 ~ 2 499 g group and 44 in ≥2 500 g group. Tei indexes were reexamined after 7 d of age in 63 preterm infants and in 31 full-term infants. The left and right ventricular Tei indexes of the ≥37 w group were less than the 32~36 w group and the <32 w group in early newborns (left ventricular: 0.382±0.069 vs. 0.431±0.069 and 0.439±0.060, right ventricular: 0.373±0.038 vs. 0.431±0.035 and 0.452±0.064); the right ventricular Tei index of the 32~36 w group was significantly less than the <32 w group ( P<0.05). No significant differences existed in the left ventricular Tei index between the 32 ~ 36 w group and the < 32 w group ( P>0.05). The left and right ventricular Tei indexes of the ≥2 500 g group were significantly less than the 1 500~2 499 g group and the <1 500 g group (left ventricular: 0.385±0.069 vs. 0.434±0.067 and 0.434±0.064, right ventricular: 0.376±0.039 vs. 0.431±0.043 and 0.450±0.061) ( P<0.05).No significant differences existed between the 1 500~2 499 g group and the <1 500 g group ( P>0.05). No significant differences existed in the left and right ventricular Tei indexes between the late newborn group and early newborn group ( P>0.05). For early newborns (1~7 d of age), the reference range of Tei index gradually decreased along with the increase of GA and BW. Conclusions:The left and right ventricular Tei indexes of full-term infants and infants with BW ≥2 500 g are less than preterm and low birth weight infants. The reference range of Tei index in early newborns shows negative correlation with GA and BW.
7.Matrix metalloproteinase-9 and neutrophil to lymphocyte ratio predict delayed perihematomal edema in patients with spontaneous intracerebral hemorrhage
Shuangshuang GU ; Dujuan SHA ; Fengjuan GAO ; Yunfei JIANG ; Jun WANG ; Jin LI
International Journal of Cerebrovascular Diseases 2021;29(2):114-119
Objective:To investigate the predictive value of matrix metalloproteinase-9 (MMP-9) and neutrophil to lymphocyte ratio (NLR) in delayed perihematomal edema (dPHE) after spontaneous intracerebral hemorrhage (sICH).Methods:Patients with sICH admitted to Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School within 24 h of onset from January 2018 to June 2020 were enrolled retrospectively. Serum MMP-9 levels and peripheral blood cell counts were detected, and NLR were calculated within 24 h of onset. dPHE was defined as an increase of 3 ml in absolute edema volume at 10-21 d after onset of sICH compared with that at 5-9 d. The demographic and baseline clinical and imaging data of the dPHE group and the non-dPHE group were compared. Multivariate logistic regression analysis was used to identify the independent predictors of dPHE. The receiver operating characteristic (ROC) curve was used to evaluate the predictive values of MMP-9 and NLR for dPHE. Results:A total of 195 patients with sICH (61.88±10.60 years old) were enrolled in the study. One hundred and forty-eight patients were males (75.9%). There were 53 patients (27.2%) in the dPHE group and 142 (72.8%) in the non-dPHE group. Univariate analysis showed that age, baseline hematoma volume, baseline National Institutes of Health Stroke Scale score, fasting blood glucose, high-sensitivity C-reactive protein, MMP-9, neutrophil count, NLR and the proportion of irregular hematoma in the dPHE group were significantly higher than those in the non-dPHE group (all P<0.05). Multivariate logistic regression analysis showed that after adjusting for confounding factors, higher MMP-9 (odds ratio [ OR] 4.291, 95% confidence interval [ CI] 2.041-6.590; P=0.007) and higher NLR ( OR 2.530, 95% CI 1.157-4.022; P=0.011) were all the independent predictors of dPHE. ROC curve analysis showed that the area under the curve of MMP-9 for predicting dPHE was 0.819 (95% CI 0.756-0.884; P<0.001), the optimal cut-off value was 164.0 μg/L, and the sensitivity and specificity were 86.79% and 66.90% respectively. The area under the curve of NLR for predicting dPHE was 0.788 (95% CI 0.719-0.856; P<0.001), the optimal cut-off value was 5.683, and the corresponding sensitivity and specificity were 77.36% and 71.13% respectively. Conclusions:sICH patients with higher baseline MMP-9 and NLR are more likely to develop dPHE. Early detection of MMP-9 and NLR in peripheral blood after admission can predict dPHE.
8.Research Progress on Electrochemical Biosensors for Breast Cancer Detection Based on Nanomaterials.
Kai FAN ; Yan ZHENG ; Dujuan LI ; Chang SU ; Gaofeng WANG
Chinese Journal of Medical Instrumentation 2020;44(6):525-531
Breast cancer is one of the most serious diseases threatening women's life and health in the world, and the mortality rate is the second in the world. With the progress of nanotechnology and the advantages of nanomaterials in the field of electrochemistry and biosensor, various nanomaterials have been applied in electrochemical biosensors. This makes the electrochemical nano-biosensor in the field of rapid detection of breast cancer has been widely concerned and studied. This paper introduces the important components of electrochemical nano-biosensor for breast cancer detection and the research progress of each component in breast cancer detection, as well as the performance of electrochemical nano biosensor in breast cancer detection and the prospect of its application.
Biosensing Techniques
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Breast Neoplasms/diagnosis*
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Electrochemical Techniques
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Female
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Humans
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Nanostructures
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Nanotechnology
9.Tranexamic acid for spontaneous intracerebral hemorrhage: a randomized controlled study
Jie NI ; Luna WANG ; Fang WANG ; Min JIANG ; Dujuan SHA
International Journal of Cerebrovascular Diseases 2020;28(4):266-270
Objective:To evaluate the safety and effectiveness of tranexamic acid in the treatment of spontaneous intracerebral hemorrhage.Methods:Patients with spontaneous intracerebral hemorrhage admitted to the Departments of Emergency and Neurology, Nanjing Drum Tower Hospital from December 2015 to December 2018 were enrolled prospectively. The patients were randomly divided into two groups according to a random number table: tranexamic acid group and control group. All patients received conventional treatment. On this basis, 1 g of tranexamic acid injection was given to the tranexamic acid group, dissolved in 100 ml of normal saline, intravenous injection for 10 min; then 1 g of tranexamic acid was given, dissolved in 250 ml of normal saline, intravenous drip for 8 h. The control group was given an equal volume of normal saline. The main outcome measures were good outcome (defined as modified Rankin Scale score0-2) and mortality at 90 d after treatment. The secondary outcome was hematoma enlargement at 24 h after treatment and the National Institutes of Health Stroke Scale (NIHSS) score at 7 and 30 days after treatment. Platelet count and fibrinogen level were measured before treatment and 4 h after the infusion of tranexamic acid. Various adverse events were monitored.Results:A total of 150 patients were included, including 83 males (55.3%). There were 73 patients in the tranexamic acid group and 77 in the control group. There was no statistically significant difference in baseline data between the two groups. The rate of good outcome in the tranexamic acid group at 90 d was significantly higher than that in the control group (57.5% vs. 40.3%; χ2=4.476, P=0.034), while there were no significant differences in mortality rate (0% vs. 1.3%; Fisher's exact test P=1.000) and the proportion of patients with hematoma enlargement at 24 h (6.8% vs. 15.6%; χ2=2.845, P=0.092). The NIHSS score at 7 d (9.26±3.35 vs. 11.68±4.25; t=3.859, P<0.001) and at 30 d (5.45±2.52 vs. 7.38±3.28; t=4.030, P<0.001) in the tranexamic acid group were significantly lower than those of the control group. Fibrinogen in the tranexamic acid group increased significantly after treatment compared with baseline (4.20±0.56 g/L vs. 3.33±0.60 g/L; t=8.997, P<0.001), and was significantly higher than that in the control group after treatment (4.20±0.56 g/L vs. 3.30±0.55 g/L; t=9.906, P<0.001). No adverse events such as venous thromboembolism, ischemic events, and seizures were observed. Conclusion:Tranexamic acid can promote the recovery of neurological function, and improve the outcome of patients with acute spontaneous intracerebral hemorrhage, and the safety is good.
10.Effect of cocaine-and amphetamine-regulated transcription peptide on synaptic formation in cultured cortical neurons subjected to oxygen-glucose deprivation
Luna WANG ; Xiang CAO ; Zhi ZHANG ; Jian QIAN ; Dujuan SHA
International Journal of Cerebrovascular Diseases 2020;28(6):433-439
Objective:To investigate the effect of cocaine- and amphetamine-regulated transcript peptide (CART) on the synapse structure of mice cortical neuron subjected to oxygen-glucose deprivation (OGD).Methods:Primary neurons of the embryonic cerebral cortex obtained from healthy and clean Kunming mice at gestational age of 16-17 d were cultured. They were divided into control group, CART group, OGD group, and OGD+ CART group. 0.4 nmol/L CART 55-102 was added and cultured for 12 h after OGD treatment in the OGD+ CART group; the CART group was given the same dose of CART 55-102. The neuronal mortality was measured by the flow cytometry. The changes of synaptic structure were observed by immunofluorescence analysis, and the axon length and synapsin Ⅰ positive area were quantitatively analyzed. Real-time fluorescent quantitative polymerase chain reaction and Western blot analysis were used to identify the brain-derived neurotrophic factor (BDNF) mRNA and protein expression. Results:Compared with the control group, the mortality of neurons in the OGD group was significantly increased, the neuronal synapse growth was significantly inhibited, the positive area of synapsin Ⅰ was significantly reduced, and the expression levels of BDNF mRNA and protein were significantly down-regulated (all P<0.05). Compared with the OGD group, adding CART 55-102 significantly reduced the mortality of OGD neurons ( P<0.05), reversed the inhibitory effect of OGD on neuronal synapse growth, significantly increased the length of neuron axons and the positive area of synapsin Ⅰ (all P<0.05), and significantly up-regulated BDNF mRNA and protein expression levels (all P<0.05). Conclusion:CART can protect the synaptic structure of mice cortical neuron subjected to OGD, and its mechanism may be related to the up-regulation of BDNF expression.

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