Background::Due to the wide variety of morphology, size, and dynamics, selecting an optimal valve size and location poses great difficulty in percutaneous pulmonary valve implantation (PPVI). This study aimed to report our experience with in vitro bench testing using patient-specific three-dimensional (3D)-printed models for planning PPVI with the Venus P-valve. Methods::Patient-specific 3D soft models were generated using PolyJet printing with a compliant synthetic material in 15 patients scheduled to undergo PPVI between July 2018 and July 2020 in Central China Fuwai Hospital of Zhengzhou University.Results::3D model bench testing altered treatment strategy in all patients (100%). One patient was referred for surgery because testing revealed that even the largest Venus P-valve would not anchor properly. In the remaining 14 patients, valve size and/or implantation location was altered to avoid valve migration and/or compression coronary artery. In four patients, it was decided to change the point anchoring because of inverted cone-shaped right ventricular outflow tract (RVOT) ( n = 2) or risk of compression coronary artery ( n = 2). Concerning sizing, we found that an oversize of 2-5 mm suffices. Anchoring of the valve was dictated by the flaring of the in- and outflow portion in the pulmonary artery. PPVI was successful in all 14 patients (absence of valve migration, no coronary compression, and none-to-mild residual pulmonary regurgitation [PR]). The diameter of the Venus P-valve in the 3D simulation group was significantly smaller than that of the conventional planning group (36 [2] vs. 32 [4], Z = -3.77, P <0.001). Conclusions::In vitro testing indicated no need to oversize the Venus P-valve to the degree recommended by the balloon-sizing technique, as 2-5 mm sufficed.

Objective To construct chimeric antigen receptors modified γδT cells targeting at BCMA(BCMA CAR-γδT)and to evaluate its efficacy of anti-multiple myeloma in vitro.Methods Lentiviral vectors containing BCMA single-chain variable fragment were constructed and transiently transfected into 293T cells.The expression of foreign genes was verified by fluorescence microscopy and Western blot;the lentivirus was packaged and the virus titer was determined by flow cytometry.Human peripheral blood αβT cells were infected and γδT cells were examined for its infection efficiency;LDH release method was used to detect the cytotoxic activity of BCMA CAR-γδT cells against human multiple myeloma cell lines in vitro,and the difference of cytotoxic activity between CAR-γδT cells and CAR-αβT cells was compared by Incucyte S3 Live-Cell Analysis Instrument.Results Twenty-four hours after BCMA-CAR lentiviral vector was transferred into 293T cells,the expression of exogenous ZsGreen was microscopied by fluorescence microscope;CD3ζ was detected by Western blot,which showed that BCMA-CAR could be success-fully expressed.The lentivirus was packaged,collected and concentrated(virus titer of 2.23×108 Tu/mL).Infected αβT cells and γδT cells from human peripheral blood in MOI=5,and the results of flow cytometry showed that infection efficiency of αβT cells was 59.18%±2.56%,γδT cells was 48.15±9.86%.The cytotoxic activity of CAR-γδT cells against human myeloma cell lines MM1.S,H929 with high expression of BCMA and K562 cells with over-expression of BCMA was higher than that of empty vector control γδ T cells,which were signifi-cantly enhanced(P＜0.001),but there was no difference in cell lines negative for BCMA expression;Live-Cell Analysis Instrument results showed that the cytotoxic activity of BCMA CAR-γδT cells and BCMA CAR-αβT cells against H929 in vitro was significantly better than their vector control cells.There was no difference in the cytotoxic activities of BCMA CAR-γδT cells as compared with against BCMA negative cell lines,and so do BCMA CAR-T cells.Conclusions Cytotoxic activity of BCMA CAR-γδT targeting at BCMA in vitro was significantly enhanced,which is expected to serve as a novel allogeneic γδT cell product for cell a-doptive immunotherapy of multiple myeloma.

Objective To verify the function of exosomes from 293T cells over-expressing membrane-localized IL-3 in vitro,so as to lay a foundation for in vivo function verification in animal models of Alzheimer's disease.Methods Using the patented structure of the group,a recombinant IL-3 lentiviral vector was constructed and virus-infected 293T cells were packaged.Stable cell strain over-expressing IL-3 was screened.The membrane localization of IL-3 was verified by flow cytometry and immuno-fluorescence.Il-3-exosomes were purified by ultra filtration centrifugation,the exosmic morphology was observed by transmission electron microscope,the size distribution and concentration of exosomes were detected by nano-flow analysis,and the expression of IL-3 and exosome related marker proteins were detected by Western blot.The effect of BV-2 on the phagocytosis of Aβ amyloid was detected by immuno-fluores-cence.Results Through vector construction,virus infection,screening and verification of puromycin,293T cell strain with stable over-expression membrane-anchored IL-3 was obtained.The purified exosomes were collected and the structures of double-layer membrane vesicles with a diameter of 50-100 nm were observed under transmission electron microscope.Western blot results proved the presence of CD63,ALIX,TSG101 and other exosome marker proteins and these molecules were rich in IL-3 as compared with the control,that suggested the successful purifica-tion of IL-3-exosomes.The results of immuno-fluorescence assay showed that IL-3-exosomes promoted the phagocy-tosis of Aβ amyloid by BV-2 cells in vitro.Conclusions The gene modified 293T cell exosomes membrane-anchored expression of IL-3 can play a role of both IL-3 and exosomes in vitro,which promote the phagocytosis of microglia,there for provides a new idea for the clinical treatment of Alzheimer's disease.

OBJECTIVE: To analyze the distribution characteristics of emerging and reemerging Oncomelania hupensis snails after the criteria for transmission control of schistosomiasis were achieved in China, so as to provide insights into assessment of schistosomiasis transmission risk and formulation of snail control strategies during the elimination phase. METHODS: O. hupensis survey data in China from 2015 to 2021 were collected from the National Schistosomiasis Pevention and Control Information Management System, and the distribution characteristics of emerging and reemerging O. hupensis snails were descriptively analyzed. RESULTS: Emerging and reemerging O. hupensis snails were identified in China each year from 2015 to 2021, with relatively larger areas with emerging and reemerging O. hupensis snail habitats in 2016 and 2021, and relatively higher numbers of counties (districts) where emerging and reemerging O. hupensis snails were detected in 2016 and 2021. A total of 4 586.30 hm² of emerging O. hupensis snail habitats were found in 10 schistosomiasis-endemic provinces of China (except Fujian and Yunnan Provinces) from 2015 to 2021, with 96.80% in Anhui, Hunan and Hubei provinces, where marshland and lake endemic foci were predominant. A total of 21 023.90 hm² of reemerging O. hupensis snail habitats were found in 12 schistosomiasis-endemic provinces of China from 2015 to 2021, with 97.67% in six provinces of Hubei, Sichuan, Jiangxi, Jiangsu, Yunnan and Anhui, where marshland and lake and hilly endemic regions were predominant. Emerging snail habitats were found in 15.08% of all schistosomiasisendemic counties (districts) in China from 2015 to 2021, and 78.75% of all emerging snail habitats were identified in 11 schistosomiasis-endemic counties (districts), with the largest area of emerging snail habitats found in Lixian County, Hunan Province (645.00 hm²). Reemerging snail habitats were found in 47.67% of all schistosomiasis-endemic counties (districts) in China from 2015 to 2021, and 43.29% of all reemerging snail habitats were identified in 11 schistosomiasis-endemic counties (districts), with the largest area of reemerging snail habitats found in Weishan Li and Hui Autonomous County of Hunan Province (1 579.70 hm²). CONCLUSIONS Emerging and reemerging O. hupensis snails were identified in China each year from 2015 to 2021, with much larger areas of reemerging snail habitats than emerging snail habitats, and larger numbers of schistosomiasis-endemic provinces and counties (districts) with reemerging snails were found that those of provinces and counties (districts) with emerging snails. Specific snail control interventions are required tailored to the causes of emerging and reemerging snail habitats. Both emergence and reemergence of O. hupensis snails should be paid attention to in marshland and lake endemic areas, and Guangxi Zhuang Autonomous Region, Shanghai Municipality and Zhejiang Province where schistosomiasis had been eliminated, and reemergence of O. hupensis snails should be given a high priority in hilly areas. In addition, monitoring of O. hupensis snails should be reinforced in snail-free areas after flooding.
Humans ; China/epidemiology* ; Schistosomiasis/prevention & control* ; Cities ; Ecosystem ; Lakes

Purinergic P2Y Receptor Antagonists ; Consensus ; Cardiovascular System ; Cardiology ; Asia

Objective: To investigate the efficacy of neoadjuvant therapy (NAT) on HER2-positive breast cancer and to analyze their clinicopathological features. Methods: A total of 480 cases of HER2-positive breast cancer who received neoadjuvant therapy (NAT), diagnosed at the Department of Pathology of Fudan University Shanghai Cancer Center from 2015 to 2020, were retrospectively identified. Clinicopathological parameters such as age, tumor size, molecular subtype, type of targeted therapy, Ki-67 proliferation index, ER and HER2 immunohistochemical expression, and HER2 amplification status were analyzed to correlate with the efficacy of NAT. Results: Among 480 patients with HER2-positive breast cancer, 209 achieved pathology complete response (pCR) after NAT, with a pCR rate of 43.5%. Of all the cases,457 patients received chemotherapy plus trastuzumab and 23 patients received chemotherapy with trastuzumab and pertuzumab. A total of 198 cases (43.3%) achieved pCR in patients with chemotherapy plus trastuzumab, and 11 cases (47.8%) achieved pCR in patients with chemotherapy plus trastuzumab and pertuzumab. The pCR rate in the latter group was higher, but there was no statistical significance. The results showed that the pCR rate of IHC-HER2 3+patients (49%) was significantly higher than that of IHC-HER2 2+patients (26.1%, P<0.001). The higher the mean HER2 copy number in the FISH assay, the higher the pCR rate was achieved. The expression level of ER was inversely correlated with the efficacy of NAT, and the pCR rate in the ER-positive group (28.2%) was significantly lower than that in the ER-negative group (55.8%, P<0.001). The pCR rate (29.1%) of patients with luminal B type was lower than that of HER2 overexpression type (55.8%, P<0.001). In addition, higher Ki-67 proliferation index was associated with higher pCR rate (P<0.001). The pCR rate was the highest in the tumor ≤2 cm group (57.7%), while the pCR rate in the tumor >5 cm group was the lowest (31.1%). The difference between the groups was significant (P=0.005). Conclusions: HER2 copy numbers, HER2 immunohistochemical expression level, molecular subtype, ER expression level and Ki-67 proliferation index are significantly associated with pCR after NAT. In addition, fluorescence in situ hybridization results, HER2/CEP17 ratio and tumor size could also significantly affect the efficacy of NAT.
China ; In Situ Hybridization, Fluorescence ; Ki-67 Antigen ; Neoadjuvant Therapy ; Retrospective Studies ; Trastuzumab ; Humans ; Female ; Breast Neoplasms/drug therapy*

Humans ; Sarcoma ; NFATC Transcription Factors ; RNA-Binding Protein EWS

Animals ; Mice ; Colon ; Histological Techniques

Humans ; Carcinoma, Squamous Cell/pathology* ; Chromosomal Proteins, Non-Histone/genetics* ; Ear, Middle/pathology* ; Poly-ADP-Ribose Binding Proteins ; Nuclear Proteins

Humans ; Glomerulonephritis, Membranoproliferative/pathology* ; Fibronectins