1.Research advances in cancer therapy of cisplatin liposome
Weixuan ZHAO ; Xue LU ; Ruilin ZHAO ; Yanmei ZHANG ; Ye YANG ; Deying CAO
China Pharmacy 2025;36(3):356-361
Chemotherapy based on cisplatin or its combination therapy is a common cancer treatment method. However, the non-specific side effects of cisplatin, poor pharmacokinetic properties of small molecule drugs, and susceptibility to drug resistance greatly limit the clinical application of cisplatin as first-line anti-tumor drug. With the development of nanocarrier technology, liposomes have become an ideal carrier for delivering cisplatin drugs due to their excellent properties of targeting, reducing toxicity, and enhancing efficacy. This paper reviews the status of cisplatin liposome both domestically and internationally which have entered clinical trials, including L-NDDP,SPI-077®, Lipoplatin®,LiPlaCis,SLIT and ILC, etc. Currently, only Lipoplatin® and ILC are showing good potential in cancer therapy. Although cisplatin liposome has made some progress in reducing systemic toxicity and improving treatment efficiency in clinical research, there is still potential for further improvement in tumor targeting and reducing side effects. In the future, more low-toxicity and efficient cisplatin liposomes can be developed through formulation technologies such as co-delivery liposome, stimuli-responsive liposome and targeting liposome.
2.Generation of an induced pluripotent stem cell line from a patient with surfactant metabolism dysfunction carrying ABCA3 mutations
Zhichen TIAN ; Xin XIE ; Jinghan CHI ; Jia CHEN ; Danhua ZHAO ; Yanmei HE ; Xiaojuan YIN
Chinese Journal of Applied Clinical Pediatrics 2024;39(2):98-103
Objective:Induced pluripotent stem cells (iPSCs) cell lines were established using peripheral blood mononuclear cells (PBMCs) from a patient suffering from neonatal respiratory distress syndrome (NRDS) who carried Adenosine triphosphate-binding cassette transporter A3 ( ABCA3) compound heterozygous mutations. Methods:Cell experimental research.Peripheral venous blood was collected and PBMCs were isolated and cultured in vitro. PBMCs were transfected with non-integrated Sendai vector carrying reprogramming factors.The chromosome karyotypes of the established iPSCs were analyzed.Immunofluorescence and flow cytometry were used to detect pluripotency markers of stem cells and verify their differentiation potential.Sanger sequencing was performed to analyze gene mutations.In addition, short tandem repeat (STR) analysis was performed, polymerase chain reaction(PCR) and agarose gel electrophoresis were used to detect virus residual. Results:Karyotype analysis of established iPSCs cell lines showed normal diploid 46, XY karyotype.Immunofluorescence showed positive staining of stem cell pluripotency markers OCT4, SSEA4, Nanog and Sox2.Flow cytometry was used to detected stem cell pluripotency markers and showed expression of TRA-1-60, SSEA-4 and OCT4.After differentiation into all three germ layers, immunofluorescence was performed to detect ectoderm (Pax-6), mesoderm (Brachyury) and endoderm alpha-fetoprotein markers, and the results showed positive staining, which confirmed that the iPSCs had the potential to differentiate.Sanger sequencing showed c. 3997_3998del and c. 3137C>T compound heterozygous mutations.STR analysis showed they originate from PBMCs, and no Sendai virus residual was detected by PCR and agarose gel electrophoresis.Conclusions:In this study, PBMCs from patient carrying ABCA3 compound heterozygous mutations was used to establish iPSCs cell lines.The research lays a foundation for the study of pathogenesis, therapeutic drug screening and cell therapy of NRDS caused by ABCA3 gene mutations.
3.Trajectories and influencing factors of post-traumatic stress disorder in women with multiple in vitro fertilization embryo transfer failures
Yanhua SUN ; Jing ZHAO ; Yanmei HU ; Xia WANG ; Xiaohui SHENG ; Xiaoyue ZHANG
Chinese Journal of Practical Nursing 2024;40(2):129-136
Objective:To explore the potential categories of post-traumatic stress disorder (PTSD) trajectories in women with multiple in vitro fertilization-embryo transfer (IVF-ET) failures, and to analyze the effects of different demographic characteristics and psychological factors on the potential categories of PTSD trajectories.Methods:This was a prospective empirical research, from May 2021 to October 2022, women with IVF-ET failure ≥ 2 times in the reproductive department of Shanghai First People′s Hospital from May 2021 to October 2022 were selected as the research objects. Post-traumatic stress disorder civilian version scale was used for 4 follow-ups at 3 d (T1), 10 d (T2), 20 d (T3) after the last transplantation failure and 3 d before the next transplantation cycle (T4). Telephone follow-up and online follow-up were combined to obtain the PTSD level at 4 time points. Potential categories of PTSD score trajectories at four time points were identified using a latent category growth model, and analyze influencing factors using unordered multi classification logistic analysis.Results:Totally 196 IVF-ET women were admitted, aged (29.42 ± 4.13) years. Three PTSD trajectories were fitted in this study, including 82 cases (42%) in non-PTSD group, 61 cases (31%) in mild PTSD group and 53 cases (27%) in elevated PTSD group. Logistic regression analysis showed that age, education level, fertility pressure and marital adjustment level were the predictors of PTSD trajectory in women with multiple IVF-ET failures. Compared with the non-PTSD group, women aged ≥35 years, with lower education level and marital adjustment level were more likely to enter the elevated PTSD group ( OR=4.570, 8.540, 0.949, all P<0.05). Women aged 35 years and with greater reproductive pressure were more likely to enter the mild PTSD group ( OR=3.871, 1.063, both P<0.05). Conclusions:There is group heterogeneity in the trajectories of PTSD in women with multiple IVF-ET failures in the next transplantation cycle. Old age, low education level, high fertility pressure and poor marital adjustment can predict the trajectories of PTSD. Fertility stress and marriage adjustment are changeable variables. Medical staff can relieve women′s fertility pressure through health education and mindfulness intervention, promote a good state of marriage adjustment, and minimize the adverse effects of PTSD on the next cycle of conception.
4.Finite element analysis of effects of sagittal cervical manipulation on intervertebral disc and facet joints
Yuanbiao WEI ; Zhan LIN ; Yanmei CHEN ; Tenghui YANG ; Xiao ZHAO ; Yangsheng CHEN ; Yanhui ZHOU ; Minchao YANG ; Feiqi HUANG
Chinese Journal of Tissue Engineering Research 2024;28(6):827-832
BACKGROUND:Among the pathogenic factors of cervical spondylosis,herniation of the intervertebral disc,dislocation of the facet joint and the stenosis of the intervertebral foramen are important factors leading to symptoms in patients.Moreover,inappropriate manipulation may aggravate the possibility of cervical disc rupture,leading to exacerbation of symptoms in patients. OBJECTIVE:To compare the effect between sagittal cervical manipulation and traditional cervical rotation manipulation on the area of the intervertebral disc,facet joint and intervertebral foramen at the operative segment by the finite element analysis. METHODS:The neck CT data of a male volunteer with a normal neck were selected and imported into Mimics 17.0 three-dimensional reconstruction software.Geo-magic Studio 12.0,Solidworks 2017 and Ansys Workbench 17.0 software were used for the construction of the finite element model of cervical vertebrae(C3-6)including intervertebral disc and articular cartilage.The lower end plate of the C5 vertebral body was fixed.A uniformly distributed vertical downward 50 N load was applied on the upper surface of the upper vertebral body(C3).The stress,deformation and deformation direction of the C4-5 intervertebral disc,joint capsule stress,the displacement of facet joints and the area of bilateral intervertebral foramen were compared between sagittal cervical manipulation and traditional rotation reduction. RESULTS AND CONCLUSION:(1)When using the rotation technique,the maximum normal equivalent stress(von Mises stress)of the C4-5 disc was 8.06 MPa;the total deformation was 1.05 mm,and the fiber ring expanded to the left and outside.When using the sagittal tip lifting technique,the maximum normal equivalent stress(von Mises stress)of the C4-5 disc was 2.60 MPa;the total deformation was 0.90 mm,and the fiber ring expanded to the left and back.Compared with the rotation technique,the pressure of the cervical manipulation technique on the disc was less(about 32.3%of the rotation technique),and the deformation degree of the disc was also light(about 85.7%of the rotation technique).(2)When the rotation technique was used,the maximum stresses of the left and right articular capsule ligaments were 0.37 MPa and 1.69 MPa,respectively.The overall displacement of the facet joint was 2.21 mm.The area of the right intervertebral foramen decreased by about 3.8%and the area of the left intervertebral foramen increased by about 0.9%.When the sagittal end lifting manipulation was performed,the maximum stresses of the left and right articular capsule ligaments were 0.27 MPa and 1.70 MPa,respectively;the overall displacement of the facet joint was 1.63 mm;the area of the right intervertebral foramen increased by about 2.6%,and the area of the left intervertebral foramen decreased by about 0.9%.Compared with rotation manipulation,sagittal end lifting manipulation had fewer changes in the displacement of facet joint,joint capsule stress and intervertebral foramen area,so it was safer to operate.(3)In conclusion,compared with cervical rotation manipulation,sagittal end lifting manipulation has fewer changes in facet joint displacement,intervertebral disc stress/deformation degree,joint capsule stress,and foraminal area.In clinical practice,more appropriate manipulation should be selected based on biomechanical results after an accurate assessment of patients'conditions.
5.Inhibitory Effect of Curcumin and Its Derivatives on TGF-β Induced Fibrosis of LX-2 Cells
Yidan SHAO ; Tingting SHI ; Yanmei ZHAO ; Xi ZOU ; Jianjun XI ; Jing ZHANG ; Xiaojie JIANG ; Rangxiao ZHUANG
Chinese Journal of Modern Applied Pharmacy 2024;41(13):1750-1757
OBJECTIVE
To study the inhibitory effect and mechanism of curcumin and its derivatives A and B on TGF-β induced LX-2 cell fibrosis.
METHODS
Established the liver fibrosis model of LX-2 cells induced by TGF-β(10 ng·mL−1).The effects on cell proliferation were detected by CCK-8. The effects on cell apoptosis was detected by flow cytometry. The effects on fibrosis related factors(Collagen I, Collagen Ⅳ, Fibronectin, Vimentin, α-SMA, PDGFRβ, TGFβR1, TGFβR2, MMP2, MMP9, TIMP1 and TIMP2) protein expression and gene transcription levels were detected by Western blotting and q-PCR.
RESULTS
The curcumin and its derivative A and B had the inhibition effects on normal LX-2 cells, and the IC25 values were 15.7, 2.6, 10.2 μmol·L−1, respectively. Compared to the model group, the curcumin(15.7 μmol·L−1) and its derivative A(2.6 μmol·L−1) and B(10.2 μmol·L−1) had the significant inhibition effects on cell proliferation of the TGF-β induced LX-2 cells(P<0.05). The cell apoptosis rate of curcumin derivative B group was higher than the model group(P<0.05). Collagen I, Fibronectin, Vimentin, α-SMA, TGFβR1 and TIMP-1 protein expression levels in curcumin group were lower, while the protein expression level of MMP-9 was higher(P<0.05). The protein expression levels of Collagen I, Collagen IV, Fibronectin, Vimentin, α-SMA, TIMP-1 and TIMP-2 in curcumin derivative A group were lower, while the protein expression level of MMP-2 was higher(P<0.05). The protein expression levels of Collagen I, Collagen IV, Fibronectin, Vimentin, α-SMA, PDGFRβ, TGFβR1, TGFβR2, TIMP-1 and TIMP-2 in curcumin derivative B group were lower, while the protein expression level of MMP-2 was higher(P<0.05). The gene transcription levels of Collagen I, Fibronectin, α-SMA and TIMP-1 in curcumin group were lower(P<0.05). The gene transcription levels of Collagen I, Fibronectin and α-SMA in curcumin derivative A and B groups were lower(P<0.05).
CONCLUSION
Curcumin and its derivatives A and B inhibit the abnormal activation and proliferation of TGF-β-induced LX-2 cells, inhibit the excessive secretion and accumulation of its extracellular matrix components, and promote its degradation, thus playing an anti-fibrotic effect in vitro, especially the curcumin derivative B.
6.Synthesis and Cytotoxicity Evaluation of Panaxadiol Derivatives
Hong PU ; Chengmei DONG ; Cheng ZOU ; Qing ZHAO ; Wenyue DUAN ; Yanmei CHEN ; Lianqing ZHANG ; Jianlin HU
Chinese Journal of Modern Applied Pharmacy 2024;41(13):1765-1774
OBJECTIVE
To obtain stronger cytotoxic activity of panaxadiol derivatives.
METHODS
The 3-amino panaxadiol was prepared by the bioelectronic isosteric principle, and then 18 derivatives of cinnamic acid, NO donor and other types of panaxadiol derivatives were synthesized, among them, 12 compounds had not been reported in the literature, and their structures had been confirmed by 1H-NMR, 13C-NMR and mass spectrometry. These compounds were evaluated for their cytotoxic activity by MTS assay against human leukemia cell line HL-60, liver cancer cell line SMMC-7721, lung cancer cell line A-549, breast cancer cell line MCF-7, and colon cancer cell line SW480.
RESULTS
These results showed that compounds 6c, 7 as well as 7j exhibited potent inhibitory activities against all five tumor cells, especially the IC50 values of compound 7 against HL-60 and SMMC-7721cells were 3.41 and 4.51 μmol·L−1, respectively. It was significantly superior to panaxadiol in cytotoxicity.
CONCLUSION
These results show that 7 and 7j can be used as promising lead compounds for further research.
7.A Case Report of Myotonic Dystrophy Type 1 Presenting as Acute Respiratory Failure
Yiqi WANG ; Jie LIN ; Jianying XI ; Sushan LUO ; Yanmei ZHENG ; Chongbo ZHAO
JOURNAL OF RARE DISEASES 2024;3(2):232-236
Myotonic dystrophy type 1(DM1)is a multisystem trinucleotide repeat expansion disorder usually referred to the department of neurology with complaints of progressive muscle weakness and myotonia.This article reported a 33-year-old female patient with DM1 presenting with acute respiratory failure.Muscle bi-opsy in vastus lateralis showed significantly increased internal nuclei.Genetic test show CTG repeat expansions with the size of(847±76)in dystrophia myotonica protein kinase(DMPK)gene on chromosome 19.This case report broadens the clinician's understanding of the atypical clinical manifestations of DM1,so as to avoid missed diagnosis and misdiagnosis.
8.Attenuation of Airway Inflammation and Airway Remodeling in Ovalbumin Asthmatic Rats by Artemisinin through PI3K/Akt Signaling Pathway
Yanmei WANG ; Yanchang LIANG ; Dekun GAN ; Runyang ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(13):114-119
ObjectiveTo investigate the molecular mechanism of action of artemisinin in attenuating asthmatic airway inflammation and airway remodeling through the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway. MethodFifty male SD rats were randomly divided into blank group, model group, and low-dose, medium-dose, and high-dose groups of artemisinin, with 10 rats in each group. The ovalbumin (OVA)-induced asthma model of the rats was established, and after successful modeling, the blank group and model group received tail vein injection of 1.0 mL·kg-1 normal saline, while the low-dose, medium-dose, and high-dose groups of artemisinin received tail vein injection of 12.5, 25, and 50 mg·kg-1 artemisinin daily for seven days. Airway resistance was measured by the acetylcholine chloride method. Cell number and species changes in the alveolar lavage fluid of each group were determined by flow cytometry. Morphological changes in airway endothelial tissue were determined by the hematoxylin-eosin (HE) staining method. Apoptosis was determined by CytoTox 96 method, and enzyme-linked immunosorbent assay (ELISA) method was used to determine the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, interleukin-1β (IL-1β), and interleukin-10 (IL-10) expression. Western blot method was used to detect the (p)-PI3K/p-Akt level in the alveolar bronchial tissue of each group. ResultCompared with the blank group, the total number of cells, total number of macrophages, total number of eosinophils, total number of lymphocytes, and total number of neutrophils were significantly higher in the model group (P<0.05). HE staining showed that the airway mucosa of the rats had obvious edema, and a large number of inflammatory cells were infiltrated (P<0.05). The rate of apoptosis was significantly higher (P<0.05), and the levels of the inflammasome NLRP3, IL-1β, and IL-10 increased significantly (P<0.05). p-PI3K/p-Akt level increased significantly (P<0.05). Compared with the model group, the total number of cells, total number of macrophages, total number of eosinophils, total number of lymphocytes, and total number of neutrophils were significantly decreased after the intervention of artemisinin at low, medium, and high concentrations (P<0.05). HE staining showed that the degree of edema of the airway mucosa of the rats was reduced, and the area of the inflammatory cell infiltration was drastically reduced (P<0.05). The apoptosis rate was significantly reduced (P<0.05), and the levels of the inflammasome NLRP3, IL-1β, and IL-10 decreased significantly (P<0.05). p-PI3K/p-Akt level decreased significantly (P<0.05). ConclusionArtemisinin significantly inhibits NLRP3 inflammasome activation, reduces cellular pyroptosis and inflammatory cell expression, and attenuates airway inflammatory manifestations and airway remodeling in asthmatic rats, which may be related to the regulation of p-PI3K/p-Akt, and the results may provide laboratory insights and basis for the treatment of bronchial asthma with artemisinin.
9.Therapeutic effect of intraovarian injection of autologous platelet-rich plasma for the treatment of diminished ovarian reserve
Hongbo WU ; Yanmei LIU ; Zhao ZHANG ; Liling LIU
Chinese Journal of Blood Transfusion 2024;37(9):998-1002
【Objective】 To explore the effectiveness of intraovarian injection of platelet-rich plasma(PRP) in the treatment of patients with diminished ovarian reserve(DOR), aiming to provide new diagnostic and therapeutic ideas for the treatment. 【Methods】 A total of 22 patients with DOR who underwent autologous PRP ovarian injection at the Reproductive Medical and Genetic Center of Qinzhou Maternal and Child Health Hospital from January 2021 to December 2023 were collected. Among them, 12 patients underwent assisted reproductive technology for pregnancy. The patient′s anti-Müllerian hormone (AMH), antral follicle count (AFC), basal follicle-stimulating hormone (FSH), basal luteinizing hormone (LH) and basal estradiol (E2) levels were observed. 【Results】 The levels of AMH, AFC, basal FSH, basal LH and basal E2 in 22 patients improved after treatment compared with those before treatment. Of the 12 patients who received assisted reproduction, 2 had IVF cycle canceled due to poor ovarian reaction. Ten patients obtained embryos, of which 5 obtained high-quality embryos. 【Conclusion】 Intraovarian injection of autologous PRP can effectively improve ovarian reserve function in patients with DOR.
10.Application and analysis of enzyme immunoassay quality monitoring indicators in blood station laboratories
Jing LIU ; Jingjing WANG ; Yanmei ZHAO
Chinese Journal of Blood Transfusion 2024;37(9):1052-1057
【Objective】 To evaluate the quality of laboratory testing using anti-HIV ELISA quality monitoring indicators and continuously improve laboratory testing capabilities. 【Methods】 The data of our blood testing laboratory from July 1, 2020 to December 31, 2022 using laboratory quality monitoring indicators were analyzed, including the reaction sample size and reaction rate of initial test and the reaction sample size and compliance rate of retest. The indoor quality control data of two anti HIV ELISA reagents (Xinchuang and Wantai) during the above time period were collected. A line chart or scatter box chart was drawn to monitor the long-term trends and identify the reasons. Inter-laboratory capability comparison and evaluation with the data from the quality monitoring index evaluation report of the National Health Commission′s Clinical Inspection Center and the National Blood Station Blood Testing Laboratory during the same period was conducted. 【Results】 From July 1, 2020 to December 31, 2022, the initial reaction rates of Xinchuang and Wantai anti HIV ELISA reagents were 0.052% and 0.080%, respectively (P<0.05), and the retest compliance rates were 43.97% and 73.39%, respectively (P<0.001). The linear mean trend of the retest compliance rate of innovative reagents is close to the national average retest compliance rate of the same group, while the retest compliance rate of Wantai reagents is higher than the national average retest compliance rate of the same group reagents. The usage rates of the two reagents are lower than the national average for the same group of reagents. The average dispersion of indoor quality control values between different batches of innovative reagents is greater than that of Wantai reagents, but the dispersion of indoor quality control CV between different batches of reagents is similar. 【Conclusion】 Longitudinal analysis of long-term testing data in our laboratory through laboratory quality monitoring indicators and horizontal comparison of laboratories with the same reagents nationwide are able to promptly identify problems in the laboratory, therefore help correct the problems and continuously improve the laboratory′s quality management system, further enhancing the laboratory′s testing capabilities.


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