1.Nanoplastics aggravate severe asthma by inducing DNA damage of alveolar type Ⅱ epithelial cells
Zelun SHI ; Qing WANG ; Wen HE ; Weijia FU ; Yingwen WANG ; Xiao HAN ; Xiaobo ZHANG
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(11):1391-1405
Objective·To explore the effects and possible molecular mechanisms of nanoplastics(NPs)on severe asthma.Methods·A mouse model of severe asthma was established by using house dust mite(HDM)and lipopolysaccharide(LPS)co-stimulation.Polystyrene nanoplastics(PS-NPs)were instilled into the severe asthma mice's airways.Subsequently,bronchoalveolar lavage fluid(BALF)was collected and lung tissue sections were prepared.Flow cytometry,hematoxylin-eosin(H-E)staining,periodic acid-Schiff(PAS)staining,immunohistochemistry,and terminal dexynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)staining,were used to observe the effects of PS-NPs on airway inflammation,mucus secretion,alveolar structure,and the proliferation and apoptosis of alveolar type Ⅱ epithelial cells(AT2 cells)in severe asthma mice.The CCK-8 assay and Annexin Ⅴ/PI double staining were performed to evaluate the effects of PS-NPs on the proliferation and apoptosis of the mouse AT2 cell line MLE-12.DNA damage in AT2 cells caused by PS-NPs was detected by using anti-γ-H2A.X immunofluorescence staining.The expression of genes in the ATR/Chk1/p53 signaling pathway was detected by real-time fluorescent quantitative polymerase chain reaction(qPCR),Western blotting,Tyramide signal amplification(TSA)multiplex immunofluorescence staining,and immunofluorescence co-localization,respectively.The ATR-specific inhibitor Ceralasertib(AZD6738)was administrated to MLE-12 cells in combination with PS-NPs to evaluate the recovery effect on cell proliferation and apoptosis.Results·Flow cytometry revealed that exposure to PS-NPs increased the total number of inflammatory cells and the number of each type of inflammatory cells in the BALF of mice with severe asthma,with a predominance of neutrophils.H-E and PAS staining showed significant increase in airway inflammatory cell infiltration and mucus secretion,as well as disruption of alveolar structure.In vitro,the CCK-8 assay demonstrated significant,dose-dependent inhibition of MLE-12 cell proliferation by PS-NPs.The Annexin V/PI double staining assay indicated a higher apoptosis rate of(56.20±3.84)%in PS-NP-exposed cells compared to(23.22±2.52)%in the control group.Immunofluorescence staining demonstrated that PS-NPs were phagocytosed by MLE-12 cells and localized around the nucleus.TUNEL staining confirmed enhanced apoptosis in AT2 cells in vivo.The immunofluorescence assay revealed that compared to the control group,the expression of the DNA damage marker γ-H2A.X increased in the experimental group.qPCR,Western blotting,and TSA multiplex staining results showed that PS-NP-induced elevated expression of mRNA and proteins was related to the ATR/Chk1/p53 pathway in MLE-12 cells.Moreover,immunofluorescence co-localization also confirmed the induction of ATR and p53 proteins in AT2 cells in vivo.The ATR-specific inhibitor Ceralasertib partially restored the PS-NP-induced inhibition of cell proliferation and enhancement of apoptosis in MLE-12 cells.Conclusion·NPs exposure leads to DNA damage in AT2 cells,activating the ATR/Chk1/p53 signaling pathway and exacerbating airway inflammation and alveolar damage in mice with severe asthma.
2.Role of neuroinflammation and white matter injury in cognitive dysfunction after subarachnoid hemorrhage
Yunchuan CAO ; Bo ZENG ; Xiaoguo LI ; Yajun ZHU ; Xiaofeng ZHANG ; Yingwen WANG ; Xiaochuan SUN ; Zongduo GUO
Chongqing Medicine 2024;53(11):1732-1736
Subarachnoid hemorrhage (SAH) is the third common type of stroke in the world,and its mortality and disability rates have declined over the past few decades due to the advances in neuroimaging technology and endovascular interventional therapy and promotion of healthy physical examination,but long-term neurological deficits and cognitive impairment of the patients have not significantly improved,which may be related to the white matter injury (WMI) after SAH.Little attention has been paid to WMI after SAH in the past,which may be an important reason for the poor prognosis of the patients with SAH.The neuroin-flammation response is an important pathophysiological process after SAH,and the neuroinflammation after SAH can aggravate WMI.This article reviews the relationship between neuroinflammation and WMI after SAH in order to deepen the understanding of its effects on cognitive function after SAH.
3.Progress of Research on Clinical Value of NLR and PLR in Ulcerative Colitis
Li SHI ; Yingwen LI ; Min LIU ; Ya ZHENG ; Yuping WANG ; Qinghong GUO
Chinese Journal of Gastroenterology 2024;29(1):46-50
Ulcerative colitis is a common disease of the digestive system in China,which seriously affects the quality of life of patients due to its disease characteristics,such as easy recurrence,repeated course of disease and carcinogenic tendency.Neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)are considered as new inflammatory biomarkers,which have been found to be related with ulcerative colitis.This article reviewed the clinical value of NLR and PLR in ulcerative colitis.
4.Teprenone alleviates LPS-induced inflammatory response and cardiac dysfunction through E3 ubiquitin ligase CHIP
Liting XU ; Yingwen LIU ; Jianling LI ; Wan LIN ; Miao WANG ; Lei YU ; Xue ZHANG ; Hang LI ; Huadong WANG ; Xiuxiu LÜ ; Yiyang WANG
Chinese Journal of Pathophysiology 2024;40(5):862-871
AIM:To explore the therapeutic effect of teprenone(geranylgeranylacetone,GGA)on lipopolysac-charide(LPS)-induced cardiac dysfunction and its mechanism.METHODS:(1)Eight-week-old male C57BL/6 wild-type mice and carboxyl terminus of heat shock protein 70(HSP70)-interacting protein(CHIP)gene knockout mice were randomly divided into control group,LPS group,LPS+GGA group and GGA group,with 8 mice in each group.The model was established by intraperitoneal injection of LPS(25 mg/kg),and 1 h after LPS stimulation,mice were given intraperito-neal injection of GGA(100 mg/kg).The technique of high-resolution ultrasonography system was used to evaluate the car-diac function of mice.The serum of mice from each group were collected to detect the levels of creatine kinase-MB(CK-MB)and lactate dehydrogenase(LDH).HE staining was performed to observe histological changes of cardiac tissues.ELISA was used to detect the levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in cardiac tissues.West-ern blot was used to detect the protein levels of HSP70,CHIP,karyopherin-α 2(KPNA2),myeloperoxidase(MPO),vas-cular cell adhesion molecule(VCAM),intercellular cell adhesion molecule(ICAM),and nuclear factor-κB(NF-κB)in cardiac tissues.(2)In vitro cell inflammation model was established using mouse myocardial cells HL-1 stimulated with LPS.ELISA was used to detect the levels of TNF-α and IL-6 in cell supernatants.Western blot was used to detect the pro-tein expression levels of HSP70,CHIP,and KPNA2 in myocardial cells.Immunofluorescence staining was performed to observe the content of nuclear NF-κB.RESULTS:(1)GGA effectively improved cardiac function of LPS-stimulated mice,significantly increased ejection fraction and left ventricular fractional shortening(P<0.01),reduced serum levels of CK-MB and LDH(P<0.01),and alleviated myocardial injury.(2)GGA significantly reduced the release of TNF-α and IL-6 caused by LPS(P<0.01),as well as nuclear translocation of NF-κB,decreased the levels of KPNA2,MPO,VCAM and ICAM in cardiac tissues,and increased the levels of HSP70 in cardiac tissues and cells(P<0.01).(3)In CHIP knockout myocardial cells and mice,GGA failed to inhibit LPS-induced inflammatory response and lost its effect on im-proving cardiac function.CONCLUSION:The protective effect of GGA against LPS-caused cardiac dysfunction of mice is related to increasing expression of HSP70 and promoting CHIP activation,which inhibits the translocation of NF-κB into nucleus and suppresses inflammatory factor release.CHIP knockout abolishes the effects of GGA on reducing LPS-induced inflammatory response and myocardial injury.
5.Status quo of the selection of intravenous infusion devices in hospitalized children
Qingqing ZHANG ; Ying GU ; Yingwen WANG ; Chunmei LU ; Meijing KONG
Chinese Journal of Modern Nursing 2024;30(14):1923-1927
Objective:To investigate the status quo of intravenous (IV) infusion device selection among hospitalized children and provide direction for improving practices related to the selection of infusion devices.Methods:A total of 1 306 hospitalized children undergoing IV infusion treatment in 11 clinical departments of Children's Hospital of Fudan University in June 2021 were selected by convenience sampling. A self-developed data collection form for the selection of IV infusion devices in hospitalized children and criteria for the appropriateness of IV infusion device selection were used to survey and evaluate the appropriateness of IV infusion device selection among these children.Results:IV infusion devices were found to have been appropriately selected in 1 137 of the 1 306 children, while these devices were inappropriately selected in 169 children. The inappropriate selection was primarily due to the improper choice of peripheral intravenous catheters (PIVC), with 155 cases involving the administration of non-peripheral compatible medications through PIVC. No significant statistical difference was found in the appropriateness of IV infusion device selection between the infant group and the child and adolescent group ( P>0.05). Significant differences were observed in the appropriateness of IV infusion device selection based on different physicochemical properties of medications and the duration of therapy ( P<0.01) . Conclusions:The standardization of IV infusion device selection among hospitalized children needs improvement. It is urgent to apply evidence from the Clinical Practice Evidence- Based Guidelines for Pediatric Intravenous Therapy regarding recommendations for IV infusion device selection, to initiate evidence application projects, and to standardize the selection of IV infusion devices.
6.Safe pregnancy and delivery in a female patient with systemic lupus erythematosus after discontinuation of dual-target chimeric antigen receptor T cells therapy.
Mingxia WANG ; Ling DING ; Min WANG ; Chanjuan ZOU ; Siyu YAN ; Yingwen LIANG ; Weijia WANG ; Shanzhi HE
Journal of Peking University(Health Sciences) 2024;56(6):1119-1125
Systemic lupus erythematosus (SLE) is a diffuse, systemic autoimmune disorder that can impact multiple organs and systems, with patients exhibiting abnormal levels of various autoantibodies and immune markers in their serum. It is currently understood that dysregulation of B cells activation plays a pivotal role in the pathogenesis of SLE, as aberrantly activated B cells produce autoantibodies that inflict damage on multiple organs through complement activation and antibody-dependent cell-mediated cyto-toxicity. Traditional therapies for SLE may prove ineffective for certain patients or lead to adverse reactions. In most instances, conventional treatment merely alleviates symptoms and necessitates lifelong immunotherapy. A limited number of clinical cases have explored chimeric antigen receptor T cells (CAR-T) therapy as a potential treatment for autoimmune diseases such as SLE. Research indicates that CAR-T can specifically target CD19 expressed on the surface of B cells and plasma cells, achieving profound depletion while minimizing drug-related side effects. This report details a female patient diagnosed with SLE and lupus nephritis who was successfully treated using dual-targeting B cells maturation antigen CAR-T by our research team; following treatment, she ceased steroid and immunomodulator use, attaining sustained remission without these medications. The patient was a 23-year-old female. Multiple examinations in other hospitals and in our hospital showed positive anti-double-stranded DNA (dsDNA) antibody and low complement C3. Renal biopsy in our hospital showed lupus nephritis Ⅳ-G (A/C), and National Institutes of Health (NIH) activity index (AI) score=4. She was diagnosed with "SLE, lupus nephritis (LN)". She was treated with hormones, immunosuppressants and Chinese medicine, but the effect was not good. After the CAR-T treatment, She stopped using hormones and immune agents and achieved continuous remission with zero hormones and zero immune agents. She became pregnant six months after CAR-T infusion, and gave birth to a healthy full-term, full-weight baby successfully. She is the first patient in China who successfully discontinued hormone, immune preparations and gave birth after CAR-T therapy. During the follow-up of the patient, we found that the immune indexes had basically returned to normal, and the safety was good. It indicates that CAR-T therapy may represent a promising and innovative therapeutic approach for the management of SLE. This offers hope and establishes a precedent for SLE women of childbearing age.
Female
;
Humans
;
Pregnancy
;
B-Lymphocytes/immunology*
;
Immunotherapy, Adoptive/methods*
;
Lupus Erythematosus, Systemic/therapy*
;
Lupus Nephritis/immunology*
;
Receptors, Chimeric Antigen/therapeutic use*
;
Young Adult
7.Association of folic acid with the development and progression of liver cancer
Yingwen LI ; Li SHI ; Min LIU ; Hao YUAN ; Ya ZHENG ; Yuping WANG ; Qinghong GUO
Journal of Clinical Hepatology 2023;39(3):693-698
So far, liver cancer is still a highly malignant tumor with a high incidence rate in China, and it seriously affects the life and health of Chinese people. Previous studies have shown that the development of liver cancer is associated with various factors such as virus, smoking, drinking, and nonalcoholic fatty liver disease. With continuous exploration, more and more studies have pointed out that nutritional factors and living environment are associated with the development and progression of liver cancer. Folic acid is a necessary nutrient for cell growth and reproduction, and its level in human body has an impact on the growth of tumor cells and is closely associated with liver cancer. This article reviews the research advances in the association between folic acid and liver cancer in recent years, so as to provide new reference and basis for the prevention and treatment of liver cancer.
8.The efficacy of laparoscopic ovarian cyst aspiration in the treatment of neonatal simple ovarian cyst
Cuicui WANG ; Youliang WANG ; Gamei LI ; Yingwen QI
Chinese Journal of Neonatology 2023;38(2):97-100
Objective:To study the efficacy of laparoscopic ovarian cyst aspiration in the treatment of neonatal simple ovarian cyst.Methods:From August 2019 to December 2021, infants with neonatal simple ovarian cyst receiving laparoscopic ovarian cyst aspiration in the Department of Pediatrics of Gansu Provincial Maternity and Child-care Hospital were retrospectively studied. The clinical characteristics, age of surgery, operation duration, length of hospital stay, complications and follow-up were analyzed.Results:A total of 6 full-term infants were included. Simple ovarian cysts were located on the right side of the body in 5 cases and on the left in 1 case. The average cyst diameter was (6.1±1.4) cm, the surgery were performed at 2~5 d of age, the average duration of the surgery was (18.8±2.4) min and the average hospital stay was (5.3±1.0) d. No complications occurred before or after surgery. All the 6 infants had favorable growth and development. The ovarian cysts were all enlarged again in 1 month after surgery, then gradually shrunk at 3 to 6 months after surgery and completely resolved in 2 cases.Conclusions:Neonatal simple ovarian cysts are more common on the right side of the body and laparoscopic ovarian cyst aspiration has good and safe clinical efficacy.
9.Exploration on the training model of applied undergraduate pharmacy talents under the perspective of industry education integration
Chen WANG ; Lingzhi TANG ; Lanmei CHEN ; Hongjuan BAO ; Yanan ZHANG ; Gang ZHANG ; Chuan CHEN ; Yingwen CAI
Chinese Journal of Medical Education Research 2022;21(1):27-30
This research analyzes and explores the elements of the industry education integration in the process of pharmacy talent training from two aspects: collaborative education (professional construction, curriculum co-construction, skill deepening and talent transfer) and collaborative innovation (base expansion, technological research and completion innovation). Besides, this research also explores the outstanding performance of School of Pharmacy of Xiamen Medical College in talent training of the industry education integration. The results show that through the construction of collaborative education and collaborative innovation, the elements of the industry education integration in the cultivation of pharmacy talents in the school have become increasingly prominent, and the forms have been gradually diversified, which have promotion and guiding significance for other majors in our school to develop the industry education integration.
10.Bioactive constituents of animal-derived traditional Chinese medicinal materials for breast cancer: opportunities and challenges.
Chaochao YU ; Yi LI ; Guopeng CHEN ; Chaoyan WU ; Xiuping WANG ; Yingwen ZHANG
Journal of Zhejiang University. Science. B 2022;23(7):547-563
Breast cancer is globally the most common invasive cancer in women and remains one of the leading causes of cancer-related deaths. Surgery, radiotherapy, chemotherapy, immunotherapy, and endocrine therapy are currently the main treatments for this cancer type. However, some breast cancer patients are prone to drug resistance related to chemotherapy or immunotherapy, resulting in limited treatment efficacy. Consequently, traditional Chinese medicinal materials (TCMMs) as natural products have become an attractive source of novel drugs. In this review, we summarized the current knowledge on the active components of animal-derived TCMMs, including Ophiocordycepssinensis-derived cordycepin, the aqueous and ethanolic extracts of O.sinensis, norcantharidin (NCTD), Chansu, bee venom, deer antlers, Ostreagigas, and scorpion venom, with reference to marked anti-breast cancer effects due to regulating cell cycle arrest, proliferation, apoptosis, metastasis, and drug resistance. In future studies, the underlying mechanisms for the antitumor effects of these components need to be further investigated by utilizing multi-omics technologies. Furthermore, large-scale clinical trials are necessary to validate the efficacy of bioactive constituents alone or in combination with chemotherapeutic drugs for breast cancer treatment.
Animals
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Breast Neoplasms/drug therapy*
;
Cell Cycle Checkpoints
;
China
;
Deer
;
Female
;
Humans
;
Immunotherapy

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