1.Preparation and characterization of composite delivery system of paclitaxel-loaded temperature sensitive liposome and siRNA-loaded gold nanostar
Ziting CHENG ; Ke YAO ; Wanwan LIU ; Bohui XU ; Hongyan ZHU
Journal of China Pharmaceutical University 2017;48(4):445-452
We prepared gold nanostar (GNS) through seed growth method firstly,then formation of COX-2 siRNA(siCOX-2) and GNS composite modified with polyethylene glyco (PEG),2-amino-2-deoxy-D-glucos (DG) and 9-D-arginin (9R) was prepared.Mterwords,paclitaxel temperature sensitive liposome (PTX-TSL) was prepared by film dispersion method.Finally,siCOX-2 delivery systerm (PTX-TSL-(siCOX-2(9R/DG-GNS)))was obtained by hydrosulfuryl ligand reaction between siCOX-2 (9R/DG-GNS) and PTX-TSL The successful build of siCOX-2 (9R/DG-GNS) was vetified by nuclear magnetic resonance (NMR),sodium dodecyl sulfate polyacryl amide gel electrophoresis (SDS-PAGE),and ultraviolet spectrophotometry and agarose gel electrophoresis method.Particle size of PTX-TSL-(siCOX-2(9R/DG-GNS)) was (292 ± 14) nm and Zeta potential was about -(2.59 ± 0.12) mV,which were measured by Zetasizer Nano ZS90.The morphology of PTX-TSL-(siCOX-2 (9R/DG-GNS)) measured by transmissionelectronmicroscopy showed homogeneous star structure with phospholipid bilayer on the surface,and it showed good thermal conversion efficiency under radiation of 808 nm laser.Differential scanning calorimetry test showed that PTX-TSL phase transition temperature is about 42.6 ℃.The drug loading content(using dialysis method) and encapsulation efficiency of PTX-TSL were about 7.5% and 95.4%,at the same time,the release process experiment of PTX-TSL showed that it had a good temperature sensitive release performance.It is hopeful that this siCOX-2 system can be used for reducing drug resistance of PTX and improving the treatment effect of PTX through the synergistic antitumor drug resistance effect of siCOX-2.
2.A novel hydrogen sulfide donor modulates Kir6.2 via the cyclic guanosine monophosphate- dependent protein kinase signaling pathway in one side hippocampus of epileptic rats
Danqiong LIU ; Ziting ZHU ; Sheng DU ; Peiye CHEN ; Manru GUO ; Yilong ZHANG ; Yanmei SU ; Guanqi WANG ; Pingyi XU ; Xiaoqin ZHU
Chinese Journal of Neurology 2021;54(3):242-250
Objective:To explore the effect of hydrogen sulfide (H 2S) on modulating the subunit Kir6.2 of adenosine triphosphate sensitive potassium channels via the cyclic guanosine monophosphate-dependent protein kinase (cGMP/PKG) signaling pathway in epileptic rat models. Methods:Sixty adult male SD rats were randomly divided into the following six groups (10 rats in each group) by random number table method: control, epileptic, H 2S donor, H 2S donor+epileptic, KT5823 (one inhibitor of the cyclic guanosine monophosphate-dependent protein kinase)+H 2S donor+epileptic, and glibenclamide (one inhibitor of the adenosine triphosphate sensitive potassium channels)+H 2S donor+epileptic groups. Except the control group, SD rats were intraperitoneally injected with plentylenetetrazole to make the kindling models and their behaviours were recorded including the latency period, the grade, and the duration of the first epileptic seizure according to the Racine′s standard. The waveforms of electroencephalogram (EEG) in hippocampus were also recorded during the seizure. The mRNA and protein levels of PKG and Kir6.2 in hippocampus were evaluated by Western blotting and quantitative real-time polymerase chain reaction, and the hippocampal concentrations of cGMP and phosphorylation of cyclic guanosine monophosphate-dependent protein kinase (p-PKG) were detected by enzyme linked immunosorbent assay. Results:Rats in the epileptic group showed Ⅳ-Ⅴ grade of epileptic seizure [4.500 (4.000, 4.875)], short latency period [(10.37±8.21) min] but long duration [(69.50±24.37) s] of seizure. Compared to the epileptic group, rats in the H 2S donor group showed Ⅱ-Ⅲ grade of epileptic seizure ( P=0.004), significantly longer latency period ( P<0.001), and shorter duration of seizure ( P<0.001). Compared to the H 2S donor+epileptic group, rats in the KT5823+H 2S donor+epileptic group showed Ⅲ-Ⅳ grade of epileptic seizures, significantly shorter latency period ( P<0.001), and longer duration of seizure ( P<0.001). The results of EEG showed that the wave patterns in the epileptic group were spike or sharp waves and the amplitudes were largest [(190.570±23.590) μV]. Compared with the epileptic group, amplitudes were reduced ( P<0.001) in the H 2S donor+epileptic group. PKG mRNA and PKG protein were expressed differently among all groups (PKG mRNA: n=5, H=26.714, P<0.001; PKG protein: n=5, F=30.597, P<0.001). Compared with the control group, the expression of both PKG mRNA and PKG protein was decreased (PKG mRNA: 1.000±0.001 vs 0.782±0.064, P=0.023; PKG protein: 0.550±0.037 vs 0.145±0.020, P=0.042) in the epileptic group. Besides, Kir6.2 mRNA and Kir6.2 protein were expressed differently among all groups (Kir6.2 mRNA: n=5, H=27.761, P<0.001; Kir6.2 protein: n=5, F=60.659, P<0.001). Compared with the control group, the expression of both Kir6.2 mRNA and Kir6.2 protein was decreased (Kir6.2 mRNA: 1.000±0.001 vs 0.897±0.033, P=0.004; Kir6.2 protein: 0.384±0.035 vs 0.215±0.016, P=0.024) in the epileptic group. And the concentrations of cGMP and p-PKG were decreased (cGMP: P<0.001; p-PKG: P<0.001) in the epileptic group. The results in the H 2S donor+epileptic group were up-regulated (PKG mRNA: P=0.047; PKG protein: P<0.001; Kir6.2 mRNA: P=0.011; Kir6.2 protein: P<0.001; cGMP: P<0.001; p-PKG: P<0.001) compared with the epileptic group. However, the results in the KT5823+H 2S donor+epileptic group were down-regulated (PKG mRNA: P=0.015; PKG protein: P=0.027; Kir6.2 mRNA: P=0.013; Kir6.2 protein: P=0.017; cGMP: P=0.005; p-PKG: P<0.001) compared with the H 2S donor+epileptic group. Conclusion:A possible mechanism is that H 2S prevents the epileptic seizure from modulating the subunit Kir6.2 of ATP sensitive potassium channels via the cGMP/PKG signaling pathway.
3.Disease Prevention Knowledge, Anxiety, and Professional Identity during COVID-19 Pandemic in Nursing Students in Zhengzhou, China
Yuyan SUN ; Dongyang WANG ; Ziting HAN ; Jie GAO ; Shanshan ZHU ; Huimin ZHANG
Journal of Korean Academy of Nursing 2020;50(4):533-540
Purpose:
This study aimed to evaluate nursing students’ understanding of the prevention of COVID-19, as well as their anxiety towards the disease and their perception of their professional identity in the wake of the pandemic, in Zhengzhou, China.
Methods:
A cross-sectional study was designed to investigate 474 nursing students by cluster sampling using a stratified questionnaire from February 15 to March 31, 2020. Multiple linear regression was used to identify the factors affecting professional identity. Binary and multiple logistic regression were used to identify the factors affecting anxiety.
Results:
Responders with a high level of understanding of COVID-19 and frequent use of behavioral strategies for its prevention comprised 93.2% and 30.0% of the cohort, respectively. Professional identity was significantly associated with gender and anxiety (p < .050). The prevalence of anxiety among nursing students was 12.4%. Male (odds ratio [OR] = 2.39; 95% confidence interval [CI] = 1.26~4.52), sophomores (OR = 5.30; 95% CI = 1.61~7.45), and infrequent use of prevention measures (OR = 3.49; 95% CI = 1.16~5.19) had a significant effect on anxiety.
Conclusion
Anxiety during the COVID-19 epidemic gives an adverse effect on the professional identity of nursing in students. Nursing education institutions need to provide psychological counseling services for nursing students, in addition to improving their teaching of COVID-19 prevention strategies.
4.Meta-analysis of efficacy and safety of cabozantinib in the treatment of advanced thyroid cancer
Jing ZHU ; Ji XIE ; Ziting ZHAO ; Xiaoxia HU
China Pharmacy 2023;34(22):2800-2804
OBJECTIVE To review the efficacy and safety of cabozantinib in the treatment of advanced thyroid cancer. METHODS Retrieved from PubMed, the Cochrane Library, Embase, ClinicalTrials.gov, Wanfang data, VIP, CNKI and China Clinical Trials Registry, randomized controlled trials (RCTs) about cabozantinib (trial group) versus placebo (control group) were collected from the inception to Nov. 2022. After literature screening, data extraction and quality evaluation, meta-analysis was performed by using RevMan 5.4 software. RESULTS A total of 4 RCTs were included involving 588 patients. The results of the meta-analysis showed that the progression free survival (PFS) [HR=0.24, 95%CI (0.19,0.31), P<0.000 01], objective response rate (ORR) [RR=31.46, 95%CI (6.32,156.75), P<0.000 1], the incidence of grade 3-4 adverse event (AE) [RR=2.15,95%CI (1.76,2.61),P<0.000 01], severe adverse event [RR=1.78,95%CI (1.11,2.83),P=0.02], diarrhea [RR=3.29,95%CI(1.62, 6.66),P=0.001], palmar-plantar erythrodysesthesia syndrome [RR=28.19,95%CI (12.25,64.88),P<0.000 01], and hypertension [RR=6.50,95%CI (3.90,10.83),P<0.000 01] in trial group were significantly higher than control group; there was no statistical significance in overall survival (OS) [HR=0.83,95%CI (0.67,1.02), P=0.07] or the incidence of fatigue [RR=1.25,95%CI (0.78,1.98),P=0.35] between the two groups. Subgroup analysis showed that PFS and ORR in patients with differentiated thyroid carcinoma (DTC) and medullary thyroid carcinoma (MTC) in the trial group were significantly higher than control group (P< 0.05). There was no significant difference in OS of DTC and MTC patients in the trial group compared with the control group (P> 0.05). CONCLUSIONS Cabozantinib can prolong PFS and increase ORR in patients with advanced thyroid cancer, but the incidence of AE is high.
5.The role of lung type Ⅱ epithelial stem cell differentiation in radiation-induced pulmonary fibrosis
Ziting XIAO ; Jian TIAN ; Yanyan ZHU ; Chaojie WANG ; Ning MA ; Xingnan ZHANG ; Yun ZHOU ; Jianwei ZHOU
Chinese Journal of Radiation Oncology 2020;29(12):1102-1109
Objective:To determine the role of type Ⅱ alveolar epithelial stem cells (AEC Ⅱ) in radiation-induced pulmonary injury and investigate the potential mechanism by observing the dynamic changes in the expression levels of anti-prosurfactant protein C (proSP-C) proSP-C (AEC Ⅱ biomarker), homeobox only protein X (HOPX, type I alveolar epithelial cell biomarker) or vimentin (a mesenchymal marker) and transforming growth factor β 1(TGF-β 1), a profibrotic cytokine. Methods:Eight-week old C57BL/6j female mice were exposed to X-ray thoracic irradiation. Mouse lungs were collected at 8 different time points of 24 h, 1 week, 1 to 6 months after irradiation. The histopathological changes of the lungs at different time points were observed with H& E staining to determine the time of formation of pulmonary fibrosis. In addition, the co-expression of proSP-C with HOPX or vimentin in AEC Ⅱ was confirmed by immunofluorescence staining to track AEC Ⅱ phenotypes at different injury phases following thoracic irradiation. The expression levels of those proteins and TGF-β 1 were quantitatively detected by Western blot. Results:After thoracic exposure to a single dose of 20 Gy X-ray for 3 months, the fibrotic lesions in the lungs could be noted. The co-expression of proSP-C with vimentin or HOPX could be observed in AEC Ⅱ. Western blot demonstrated that the expression levels of TGF-β 1 and those proteins were also changed along with the lung injury. Conclusion:AEC Ⅱ can be differentiated into mesenchymal-like cells after X-ray irradiation due to the up-regulated expression of TGF-β 1, which is a potential cause of radiation-induced pulmonary fibrosis.