1.Discovery of a novel thiophene carboxamide analogue as a highly potent and selective sphingomyelin synthase 2 inhibitor for dry eye disease therapy.
Jintong YANG ; Yiteng LU ; Kexin HU ; Xinchen ZHANG ; Wei WANG ; Deyong YE ; Mingguang MO ; Xin XIAO ; Xichen WAN ; Yuqing WU ; Shuxian ZHANG ; He HUANG ; Zhibei QU ; Yimin HU ; Yu CAO ; Jiaxu HONG ; Lu ZHOU
Acta Pharmaceutica Sinica B 2025;15(1):392-408
Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC50, SMS2 = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t 1/2, cornea = 1.11 h; t 1/2, meibomian glands = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.
2.Environmental exposure to electronic cigarettes and its influencing factors among vocational school students in Shanghai
Weiyi LU ; Yangzixuan ZHU ; Shuxian ZHANG ; Ming HUA ; Jingfen ZHU
Journal of Environmental and Occupational Medicine 2025;42(11):1364-1370
Background As electronic cigarettes (e-cigarettes) are becoming increasingly prevalent, adolescents are experiencing growing levels of environmental exposure to them. Investigating the status and influencing factors of such exposure is essential to inform the development of targeted tobacco control strategies for youth. Objective To investigate the environmental exposure to electronic cigarettes among vocational school students in Shanghai, identify its influencing factors, and assess its impact on e-cigarette use behavior. Methods By cluster sampling, a total of
3.Retest improvement for minipool nucleic acid testing positive samples
Yun HOU ; Qiuxia FENG ; Bei LI ; Longmu ZHANG ; Zhongsi YANG ; Shuxian JIAO
Chinese Journal of Blood Transfusion 2024;37(2):190-195
【Objective】 To analyze the correlation between the distribution interval of minipool nucleic acid testing(NAT) positive CT value and the resolution rate, so as to improve the retest model and reduce residual risk of blood transfusion. 【Methods】 The resolution testing results by Cobas S201 system of our blood center from January 2017 to December 2021 were retrospective analyzed, and the retest model was developed based on the distribution interval of CT values. For minipool NAT HBV positive samples from March 2022 to March 2023, synchronous detection was conducted by Cobas S201 and Panther detection system, and the detection results were statistically analyzed. 【Results】 From 2017 to 2021, 474 were minipool NAT positive, among which 324 were HBV positive, accounting for 68.35%. From 2017 to 2020, the proportion of HBV positive per year was significantly higher than that of HCV and HIV(P<0.05). In resolution testing, 167 were HBV repeatable positive and 157 were HBV non-repeatable positive, accounting for 51.54% and 48.46% of HBV minipool NAT positive. HBV repeatable positive samples were with three intervals: CT value≤36, 36
4.Medical Institution's Multiple Role in the Collaborative Innovation Transformation Mode of "Industry-University-Research-Medicine" on Domestic Surgical Robots.
Zhiqun SHU ; Jialu QU ; Shuxian ZHANG ; Yirou TIE ; Yuan CHE ; Junting LI ; Letong JIANG ; Huiqing SHEN
Chinese Journal of Medical Instrumentation 2023;47(5):582-586
In recent years, with the rapid development of Chinese domestic surgical robot technology and the expansion of the application market, the "industry-university-research-medicine" collaborative innovation transformation mode has gradually developed and formed. Medical institutions play an important role in multi-party cooperation with enterprises, universities, and research institutes, as well as in product planning, technology research and development, achievement transformation, and personnel training. On the basis of reviewing the current situation of the development of the "industry-university-research-medicine" collaborative innovation transformation mode of domestic surgical robots, this study explores the multiple roles played by medical institutions in this mode and challenges, further putting forward corresponding recommendations.
Humans
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Robotics
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Universities
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Medicine
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Industry
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Technology
5.Association between health literacy and depressive emotion among occupational groups in Shanghai
Weiyi LU ; Shuxian ZHANG ; Jingfen ZHU
Journal of Environmental and Occupational Medicine 2023;40(10):1183-1189
Background At present, insufficient support for enterprise health environment and career development may lead to severe depressive emotion among occupational groups. Objective To investigate current state of depressive emotion and the relationship between health literacy and depressive emotion among occupational groups in Shanghai, and to provide evidence for formulating health management measures to alleviate depressive emotion among the occupational population. Methods This cross-sectional survey, using two-stage stratified sampling, was from December 2022 to February 2023, and selected 2548 active workers from 151 enterprises in Shanghai. A total of 2489 valid questionnaires were returned, with a recovery rate of 97.68%. Health literacy, internality health locus of control, and depressive emotion were evaluated by the Health Literacy Questionnaire, the Multidimensional Health Locus of Control Scale-Internality Health Locus of Control, and the Patient Health Questionnaire Depression Scale-9 item (PHQ-9), respectively. R 4.2.2 software was used for statistical analysis, binary logistic regression model was used to analyze the association between health literacy, internality health locus of control, and the risk of depressive emotion, and multiple linear model was used to analyze the correlation between health literacy, internality health locus of control, and PHQ-9 related indicators (total score, affective score, and somatic score). Results A total of 2489 workers aged 18 years and above in Shanghai were included in the analysis, 868 of them reported depressive emotion, and the positive rate of depressive emotion was 34.9%. The total score, affective score, and somatic score of PHQ-9 in M(P25, P75) were 3.00 (0.00, 6.00), 1.00 (0.00, 4.00), and 1.00 (0.00, 3.00), respectively. The results of binary multiple logistic regression analysis showed that after adjusting for selected confounders, no health literacy (OR=1.32, 95%CI: 1.10, 1.60; P=0.004) and low level of internality health locus of control (OR=1.66, 95%CI: 1.35, 2.05; P < 0.001) were associated with an increased risk of reporting depressive emotion. The results of multiple linear model showed that the lack of health literacy and low internality health locus of control were positively correlated with the total score, affective score, and somatic score of PHQ-9. Conclusion Depressive emotion among the working population in Shanghai is prominent, and more than 1/3 of them report depressive emotion. Lower health literacy and internality health locus of control are related to an increased risk of depressive emotion in the study population. Improving occupational health literacy and enhancing internality health locus of control are expected to prevent depressive emotion in occupational groups.
6.Adverse reactions to blood transfusion: A retrospective analysis of 814 cases in Qingdao area from 2020 to 2021
Qi YU ; Xiaoxia LIU ; Hong ZHOU ; Yuqing WU ; Shuxian JIAO
Chinese Journal of Blood Transfusion 2022;35(12):1259-1262
【Objective】 To investigate the incidence and composition of adverse reactions to blood transfusion(ARBT) in Qingdao hospitals in recent years. 【Methods】 The "Statistical Table of Adverse Reactions to Blood Transfusion in Medical Institutions" issued by Qingdao Quality Control Center of Blood Transfusion throughout 2020 to 2021, involving 96 hospitals in the region, were collected and analyzed, including the number, proportion and types of ARBT, as well as the types of blood components transfused. 【Results】 From 2020 to 2021, 296 676 cases of blood transfusion in 96 hospitals occurred, and the incidence of ARBT was 0.27% (814/296 676), of which the incidence of ARBT involving plasma transfusion was 0.17% [accounting for 39.07% (318/814) of all transfusion reactions], involving platelet transfusion was 0.68% [31.08% (259/814)], involving erythrocyte transfusion was 0.11% [27.64% (225/814)] and cryoprecipitation transfusion 0.03% [1.47% (12/814)]. The types of ARBT were anaphylaxis 77.64% (632/814), fever 19.78% (161/814), transfusion-related dyspnea 1.47% (12/814), transfusion-related circulatory overload 0.37% (3/814), purpura 0.25% (2/814) and transfusion-related hypotension 0.25% (2/814), delayed hemolysis 0.12%(1/814) and acute hemolysis 0.12%(1/814), respectively. 【Conclusion】 In recent years, the incidence of ARBT in local medical institutions is lower than that of domestic general level, and the main reactions are anaphylaxis and fever following the transfusion of plasma or (and) platelets.The monitoring and control of ARBT should be strengthened in each hospital with accurate and timely report, and active preventive measures should be taken to control or reduce the incidence of ARBT effectively.
7.Nucleic acid technology(NAT) testing for blood screening: A comparative study on individual donation and minipool NAT test
Longmu ZHANG ; Lei XU ; Qiuxia FENG ; Zhongsi YANG ; Shuxian JIAO
Chinese Journal of Blood Transfusion 2021;34(1):22-26
【Objective】 To compare the detection performance of Cobas s201, a minipool(MP) nucleic acid test(NAT) system, and Panther, a individual donation(ID) NAT system, in blood donor screening. 【Methods】 NAT was conducted on 126 359 blood samples, and initially reactive (IR) samples were either discriminated or resolved by ID testing.The non-discriminated reactive (NDR) samples implicated in Panther sysytem were subjected to ID-NAT by Cobas s201. Some non-repeatable reactivet(NRR) and repeatable reactive (RR) samples implicated in Cobas s201 system were subjected to ID-NAT by Panther. 【Results】 61 MP-IR cases were implicated in a total of 85 128 samples that detected by Cobas 201, and 29(0.34‰) were RR after resolved by ID testing. 74(1.79‰)IR samples were implicated in 41 231 samples that detected by Panther, and 22 (29.73%) were DR-HBV after discriminatory test. Among the NDR 28 samples detected by Panther multiplex system, 7 were positive by Cobas s201 single sample (PP1) whereas non-reactive in simulated MPs of six by Cobas 201.In 28 RR samples resolved by Cobas 201, 24 positive and 4 negative samples were retested by Panther. Among the 11 samples presenting inconsistent retest results by Panther and Cobas 201, 10 were anti-HBc positive, carrying low viral load HBV. 【Conclusion】 The NAT-yield by Panther was significantly higher than that by Cobas s201. Some samples with negative discriminatory results were OBI, and it is necessary to further track and verify the unidentified samples. Cobas s201 is more suitable for a wide array of MP-NAT testing while Panther sample loading, which is flexible and easy to operate, is more suitable for ID-NAT with medium sample size.
8.Construction and validation of eukaryotic expression vectors for human ABO subgroup genes.
Zhihui FENG ; Bin HU ; Tongxian WANG ; Shuxian JIAO ; Shutao PANG
Chinese Journal of Medical Genetics 2018;35(1):64-68
OBJECTIVE To construct eukaryotic expression vectors for human ABO and subgroup genes A101, B101, CisAB01, Ael05, B(A)04 and Bw03, and validate their expression in vitro. METHODS Total RNA was isolated from individuals with the A101 and B101 subgroups. cDNA of A101 and B101 was synthesized by reverse transcription and amplified with specific primers. Subgroup genes CisAB01, Ael05, B(A)04 and Bw03 were then amplified with PCR for site-directed mutagenesis. Fragments of the ABO genes were directionally linked to pcDNA3.1 positive-eukaryotie expression vectors. After antibiotic screening, the sequences were analyzed. The vectors were transfected into Hela cells, and the expression of target proteins was detected by Western blotting and immunofluorescence assay. RESULTS Sanger sequencing has confirmed that pDNA3.1-A101, pDNA3.1-CisAB01, pDNA3.1-Ael05, pDNA3.1-B101, pDNA3.1- B(A)04, pDNA3.1-Bw03 positive-eukaryotic expression vector were successfully constructed. The results of Western blotting and immunofluorescence revealed clear presence of the expressed proteins. CONCLUSION Eukaryotic expression vectors for ABO subgroup genes were successfully constructed and worked well in Hela cells in vitro, which can facilitate further study of the ABO blood group proteins.
9.Intracellular Ca2+is involved in survival, proliferation and differentiation of bone marrow-derived mesenchymal stem cells into hepatocytes
Shuxian JIAO ; Bin HU ; Lin ZHAO ; Xiaohua LIU ; Zhihui FENG
Chinese Journal of Tissue Engineering Research 2013;(40):7028-7033
BACKGROUND:The mechanism of differentiation and proliferation of bone marrow-derived mesenchymal stem cells remains unclear. In addition, issues such as how signal pathways such as Ca2+and bone marrow-derived mesenchymal stem cellproliferation and differentiation signals form complex signal network remain poorly understood.
OBJECTIVE:To investigate the effect of Ca2+in the induced differentiation of bone marrow-derived mesenchymal stem cells into hepatocytes.
METHODS:Bone marrow-derived mesenchymal stem cells were isolated from rat bone marrow using whone bone marrow adherence method, purified, amplified, and induced with hepatocyte growth factor. [Ca2+]i in the directional differentiated bone marrow-derived mesenchymal stem cells and control bone marrow-derived mesenchymal stem cells were detected with flow cytometry. Bone marrow-derived mesenchymal stem cells induced with hepatocyte growth factor were mixed with nimodipine of different concentration, and cells were divided into three groups:hepatocyte growth factor+nimodipine 10 mg/L, 50 or 100 mg/L groups. cellgrowth was observed with inverted phase contrast microscope and alpha 1-antitrypsin expression of the cells was confirmed by immunocytochemistry. The calcineurin M and the activation of extracellular signal regulated kinase pathway was detected by reverse transcription-PCR and western blotting, respectively.
RESULTS AND CONCLUSION:[Ca2+]i in the directional differentiated bone marrow-derived mesenchymal stem cells was higher than in the control group (P<0.05). After addition of a larger dose of nimodipine, no differentiation of cells was obeserved and growth of bone marrow-derived mesenchymal stem cells was getting worse. There were few alpha 1-antitrypsin positive cells in the nimodipine groups. Calcineurin Mexpression was significantly increased in directional differentiated bone marrow-derived mesenchymal stem cells and smal dose of nimodipine than the controls (P<0.05). However, no significant difference was found among middle, high dose nimodipine and control groups (P>0.05). These findings indicate that Ca2+could participate in the differentiation of bone marrow-derived mesenchymal stem cells into hepatocytes incuded with cytokines, and also maintain the survival and proliferation of bone marrow-derived mesenchymal stem cells.
10.Preparation and properties of poly (acrylic ester) hydrogel as basic materials for intraocular lens.
Yuzheng XIA ; Hui LIU ; Shuxian SHI ; Xiaonong CHEN ; Shuke JIAO
Journal of Biomedical Engineering 2009;26(5):1047-1051
Poly (acrylic ester) hydrogel materials were widely used in intraocular lens and contact lens because of their excellent optical performance and biocompatibility. In this paper, the bulk copolymerization behavior of hydrophilic hydroxyethyl methacrylat with hydrophobic methyl metharylate was studied; and the optical performance, calcium deposits, equilibrium water content of polymers and its hydrogels obtained by different ratios of monomers were systematically investigated. The experimental results showed that the average light transmittance and the equilibrium water content of the obtained hydrogels increased with the increasing of the hydrophilic monomer content from 0 to 100%; however, the hardness decreased. The highest light transmittance reached 97% and the hardness of Shore A fell from 92 to 25, the equilibrium water content of hydrogel increased from 16% to 64%. The absorbent capacity of copolymers reduced with the adding of cross-linking monomer. When m(hydrophilic monomer): m(hydrophobic monomer) = 90 : 10, the combination property of the polymer and its hydrogel obtained is optimum.
Acrylic Resins
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chemical synthesis
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chemistry
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Biocompatible Materials
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chemical synthesis
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chemistry
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Humans
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Hydrogels
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chemical synthesis
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chemistry
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Lenses, Intraocular
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Polyhydroxyethyl Methacrylate
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chemical synthesis
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chemistry
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Tensile Strength

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