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    Research progress of effect of carotenoids on maternal and child health
    WU Ke1, SUN Han-xiao2, CAI Mei-qin1
       2019, 39 (8): 929-.   DOI: 10.3969/j.issn.1674-8115.2019.08.021
    Abstract669)      PDF(pc) (7354KB)(4224)       Save
    Early life nutrition plays an important role in determining the pregnancy outcomes and offspring lifelong health. Carotenoids deficiency is associated with adverse pregnancy outcomes such as preeclampsia, premature delivery and intrauterine growth restriction. Carotenoids possess antioxidant, inflammation modulating and immune-enhancing properties and promote visual, cognitive and respiratory health in offsprings. Among carotenoids, α-carotene, β-carotene and β-cryptoxanthin can be transformed into vitamin A in vivo, and their conversion rates are affectedthe nutritional status of vitamin A. Lutein and zeaxanthin are highly enriched in the brain and retina of infants and young children, which are closely related to the development of visual acuity and cognitive function. Breast milk contains an adequate level of lutein and its absorption rate is significantly higher than that of infant formulas. Consequently lutein supplementation is necessary for artificially fed infants, especially premature infants. In this paper, the functional research progresses of carotenoids related to adverse pregnancy outcomes and offspring development, as well as the present situation of carotenoids supplementation in formula were reviewed.
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    Study on Prrx1 + periodontal ligament stem cells during orthodontic tooth movement by lineage tracing
    WANG Xijun, JIN Anting, HUANG Xiangru, XU Hongyuan, GAO Xin, YANG Yiling, DAI Qinggang, JIANG Lingyong
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (8): 1008-1015.   DOI: 10.3969/j.issn.1674-8115.2022.08.005
    Abstract181)   HTML10)    PDF(pc) (4046KB)(498)       Save

    Objective ·To investigate the dynamic distribution of paired related homebox 1 (Prrx1) positive cell lineage (Prrx1+ cell lineage) in periodontal ligament stem cells (PDLSCs) during tooth movement in mice by Cre/loxP recombination system. Methods ·By using Cre/loxP recombination system, inducible Prrx1-CreERT2mice were mated with R26tdTomato fluorescently labeled mice, and their offspring mice were genotyped by PCR. Eight offspring mice were injected with tamoxifen (TA) intraperitoneally to mark the Prrx1+cell lineage (tdTomato+ cells) in PDLSCs. The orthodontics tooth movement (OTM) model was constructed by placing a force-loading device on the left side of maxilla (i.e., OTM side), and the right side without force was control side (i.e., Ctrl side). The mice were sacrificed on the third day (OTM 3 d) and the seventh day (OTM 7 d) of tooth movement, and their bilateral maxillary molars and surrounding periodontium were collected, decalcified, embedded and frozen sectioned. The changes of periodontal ligament in the tension area and compression area were observed by hematoxylin-eosin staining (H-E staining), and the dynamic distribution of Prrx1+ cell lineage was observed by immunofluorescence staining. Results ·The genotype of the offspring mice was identified by PCR as Prrx1-CreERT2;R26tdTomato . With the increased action of the stressing device, the tooth movement distance of OTM 7 d mice [(87.44±4.02) μm] increased significantly compared with that of the OTM 3 d mice [(42.81±5.04) μm], suggesting OTM model was successfully constructed. H-E staining showed that the periodontal ligament and its gap in the compression area of the OTM side was compressed and narrowed on OTM 3 d, and its width was gradually restored on OTM 7 d; the periodontal ligament in the tension area of the OTM side was stretched on OTM 3 d, and the periodontal ligament was more regularly arranged on OTM 7 d than that on OTM 3 d. Immunofluorescence staining showed that the number of tdTomato+ cells in the periodontal ligament of the compression area on the OTM side was lower than that of the Ctrl side on OTM 3 d, and the number of tdTomato+ cells in compression area on the OTM side was higher than that of the Ctrl side on OTM 7 d (both P<0.05); on both OTM 3 d and OTM 7 d, the number of tdTomato+ cells in tension area on the OTM side increased compared with that on the Ctrl side (both P<0.05). Conclusion ·The OTM model of Prrx1-CreERT2;R26tdTomato mice is successfully constructed, and the involvement of Prrx1+ cell lineage in periodontal remodeling during OTM is tentatively confirmed.

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    Preliminary study on the cellular level of SARS-CoV-2 proteins mediated by macropinocytosis pathway
    JIANG Gan, YANG Yuquan, CHEN Yaoxing, HOU Zhaoyuan, GAO Xiaoling, CHEN Hongzhuan, JIA Hao
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (8): 987-996.   DOI: 10.3969/j.issn.1674-8115.2022.08.003
    Abstract164)   HTML11)    PDF(pc) (8168KB)(456)       Save

    Objective ·To investigate the effects of several key proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on macropinocytosis in various cell models. Methods ·① The interactions between spike protein receptor-binding domain (S-RBD), nucleocapsid protein (N) and non-structural protein-7 (NSP7) of SARS-COV-2 and HEK-293T intracellular proteins were explored by co-immunoprecipitation assay. ② In vitro, S-RBD, N and NSP7 proteins of SARS-CoV-2 were incubated with HEK-293T/bEnd.3/Beas-2b cells (normal cell models), respectively, and the changes of macropinocytosis level of cells labeled with fluorescein isothiocyanate (FITC)-70 kDa-dextran were observed. ③ In vitro, S-RBD, N and NSP7 proteins of SARS-CoV-2 were incubated with inflammatory cells induced by lipopolysaccharide (LPS), respectively, and the changes of macropinocytosis level of inflammatory cells were analyzed. ④ In the normal cell models and inflammatory cell model, EIPA or lipoprotein nano-drug carriers loaded with Rab5 small interfering RNA (siRNA) were used to inhibit the macropinocytosis induced by SARS-CoV-2 proteins, respectively, and the uptake of S-RBD, N and NSP7 proteins by cells were further observed. Results ·① The three proteins of SARS-COV-2 could bind to Rab small GTPase proteins after being absorbed into cells. ② It was found that S-RBD, N and NSP7 proteins of SARS-COV-2 could induce the macropinocytosis after entering the HEK-293T/bEnd.3/Beas-2b cells. ③ Furthermore, the three proteins of SARS-COV-2 could enhance the megapinocytosis of the inflammatory cell. ④ After treatment with EIPA (75 μmol/L) or lipoprotein nano-drug carriers loaded with Rab5 siRNA, the uptake of S-RBD, N and NSP7 proteins were decreased in both types of cells. Conclusion ·S-RBD, N and NSP7 proteins of SARS-CoV-2 can up-regulate megapinocytosis levels in various cell models, especially in the case of combined inflammation infection. At the same time, macropinocytosis inhibitor / lipoprotein nano-drug carrier can inhibit the macropinocytosis up-regulated by the above proteins, and then reduce the entry levels of viral proteins.

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    Marine sponge-derived smenospongine overcomes resistance of cisplatin via inhibiting EGFR-Akt-ABCG2 pathway in NSCLC cells
    LIAO Yahui, LIU Liyun, ZHU Hongrui, LIN Houwen, YAN Jizhou, SUN Fan
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (8): 997-1007.   DOI: 10.3969/j.issn.1674-8115.2022.08.004
    Abstract171)   HTML11)    PDF(pc) (4930KB)(438)       Save

    Objective ·To explore the antitumor activities and mechanisms of the sesquiterpene amine quinone compound smenospongine (SME) in non-small cell lung cancer (NSCLC) cell line A549 and cisplatin-resistant cell line A549/DDP. Methods ·Parental cell A549 and its cisplatin-resistant cell A549/DDP were used as research models. CCK-8 assay was used to detect the half maximum inhibitory concentration (IC50) of the two cell lines treated with first-line chemotherapeutic drugs, in order to verify the multidrug resistance of A549/DDP. Colony formation assay was used to detect the effect of SME on the proliferation of parental and drug-resistant cells. Transwell invasion assay and Western blotting were used to detect the effect of SME on epithelial to mesenchymal transformation (EMT) of A549/DDP; Western blotting and quantitative real-time PCR (qRT-PCR) were used to detect the protein and mRNA expression levels of multidrug resistance genes regulated by SME in two cell lines and the molecular mechanism of drug resistance. Furthermore, Western blotting was used to detect the effect of SME on the upstream protein of multidrug resistance protein, ATP-binding cassette superfamily G member 2 (ABCG2), and flow cytometry was used to detect the effect of SME on the cell cycle of parental and cisplatin-resistant cells. TdT-mediated dUTP Nick-end labeling (TUNEL) and Western blotting were used to detect the effect of SME on apoptosis of the two cell lines. Results ·Compared with parental cells, cisplatin-resistant A549/DDP cells showed significant resistance to cisplatin and showed multidrug resistance to the first-line chemotherapy drugs used on lung cancer. SME markedly inhibited the proliferation and clone formation of A549 and A549/DDP as well as the EMT of drug-resistant cell. SME notably down-regulated the expression of ABCG2 protein and mRNA, and inhibited the epidermal growth factor receptor (EGFR)-serine/threonine kinase (Akt) signal pathway upstream of ABCG2, which thereby down-regulated ABCG2, and positively regulated FoxO1. SME induced G0/G1 arrest and induced apoptosis of both cells. Conclusion ·As a new small molecular compound in overcoming the drug resistance of NSCLC, SME inhibits the cell viability of A549 and A549/DDP by restraining EGFR-Akt signal pathway which thereby down-regulates ABCG2, positively regulates FoxO1 and inhibits EMT of A549/DDP, which finally leads to apoptosis.

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    Analysis of clinical trial research in Shanghai Jiao Tong University School of Medicine
    PENG Shutao, QIU Xiaochun
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (8): 971-979.   DOI: 10.3969/j.issn.1674-8115.2022.08.001
    Abstract197)   HTML229)    PDF(pc) (4893KB)(435)       Save

    Objective ·To analyze the discipline distribution, research teams, multi-center cooperation and trend of clinical trial registration and published papers of Shanghai Jiao Tong University School of Medicine (SJTUSM) from 2012 to 2021. Methods ·On the Dimensions, and China and US clinical trial registration platforms, the clinical trial information registered by the institutions affiliated to SJTUSM from 2012 to 2021 was retrieved. Each clinical trial was classified and marked according to the classification standards such as Health Research Classification System (HRCS) and International Commission on Radiological Protection (ICRP). Clinical trial papers published by the first author or corresponding author from SJTUSM in the same period were retrieved in PubMed. EXCEL 2016 and VOSviewer 1.6.18 software were used to conduct cluster analysis and visual summary. Results ·From 2012 to 2021, Chinese researchers participated in 54 652 newly registered clinical trials worldwide, accounting for 13.63% of the global in total. Beijing, Shanghai and Guangzhou have been the top three cities with the most clinical trials in China. The number of newly registered and underdeveloped clinical trial projects in SJTUSM has been basically increased year by year in the past 10 years, but it declined slightly in 2021. In total, 3 970 clinical trials were registered by SJTUSM, in which 44.4% were registered on the Chinese clinical trial platform and 55.0% were registered on the US clinical trial platform, and 85.5% were initiated by researchers. Cancer, cardiovascular disease, oral and gastrointestinal disease, mental disease, and metabolic and endocrine disease were the major areas of clinical trial research of SJTUSM. Lung cancer research ranked the first in all 47 kinds of tumor research. The Sixth People 's Hospital, Ruijin Hospital and Renji Hospital ranked top 3 in clinical trial registration among hospitals affiliated to SJTUSM. A total of 1 898 papers (5.4%) were published in clinical trials with SJTUSM as the first author 's or correspondent author 's institution, and the research topics were mainly distributed in the fields of gastroenterology, heart disease, tumor, radiation, orthodontics and diabetes. The affiliated hospitals of Fudan University has been the main institutions of clinical trial cooperation. SJTUSM has formed core research teams in the fields of diabetes, hypertension, orthopedics, radiology and nephrology. Conclusion ·SJTUSM has obvious advantages in clinical trial research discipline and a great potential for emerging disciplines. Innovative clinical research teams have been formed in SJTUSM. Multi-center clinical trials are the norm of clinical trials, and SJTUSM has presided over international multi-center clinical trial cooperation in some fields. However, compared with the clinical trial registration in the world and other domestic regions in 2021, the number of clinical trial registrations of SJTUSM has decreased significantly, and the reasons need to be further analyzed.

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    Comparison of mitochondria and NAD + level in the murine cochleae of C57BL/6J mice at different ages
    FENG Baoyi, DONG Tingting, ZHENG Xiaofei, TAO Yong, WU Hao
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (8): 980-986.   DOI: 10.3969/j.issn.1674-8115.2022.08.002
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    Objective ·To investigate the changes of mitochondria and nicotinamide adenine dinucleotide (NAD+) levels in the cochleae of C57BL/6J mice at different ages, and explore potential mechanism of age-related hearing loss. Methods ·Forty C57BL/6J male mice aged 1, 4, 8, 12 months, respectively, were chosen and classified into 4 groups in terms of age (n=10). Auditory brain response (ABR) and distortion product otoacoustic emission (DPOAE) were conducted to detect the auditory function of mice at different ages; real-time quantitative PCR (RT-qPCR) was applied to compare the mRNA expression levels of the genes associated with mitochondrial energy metabolism in the cochleae of mice at different ages, including Ndufb5 (NADH: ubiquinone oxidoreductase subunit B5), Sdha (succinate dehydrogenase complex flavoprotein subunit A), Sdhc (succinate dehydrogenase complex subunit C), and Atp5b (ATP synthase, H+ transporting mitochondrial F1 complex, beta subunit); the changes of mitochondrial quantity in the cochlear hair cells from the mice aged 1 month and 12 months were observed by whole-mount immunofluorescence; the mitochondrial ultrastructure in the cochlear sensory epithelia including outer and inner hair cells, myelinate nerve fibers and spiral ganglion neurons of 1- and 12-month-old mice was observed by transmission electron microscope (TEM); NAD+ levels in the cochleae of mice at different ages were detected by quantitative colorimetry. Results ·The ABR thresholds of the 12-month-old mice were significantly elevated in comparison with those of the 1-month-old mice at the frequency range of 5.66?45.00 kHz (P<0.01); and the DPOAE thresholds of the 12-month-old mice were significantly elevated in comparison with those of the 1-month-old mice at the frequency range of 11.32?32.00 kHz (P<0.01). The expression levels of the genes related to mitochondrial functions including Ndufb5, Sdha, Sdhc, and Atp5b showed a downward trend with the age, which in the 8-month-old and 12-month-old mice were significantly different from those in the 1-month-old mice (P<0.05). Immunostaining showed that the number of mitochondria in cochlear inner hair cells of the 12-month-old mice was significantly lower than that of 1-month-old mice. It was observed by TEM that vacuolar degenerated mitochondria and larger lipofuscin existed in the inner hair cells, myelinate nerve fibers and spiral ganglion neurons of the 12-month-old mice. The NAD+ level showed a decreasing trend with age, declining significantly from 8 months of age, compared with the 1-month-old mice (P<0.01). Conclusion ·Mitochondrial dysfunction with abnormal structure and descending NAD+ levels in the cochleae is consistent with hearing function deterioration in C57BL/6J aging mice.

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    Research progress of effect and mechanism of protein arginine methyltransferase in tumors
    WEN Jun, MIN Xue-jie, ZHAO Li, ZHAO Xiao-ping
       2017, 37 (6): 842-.   DOI: 10.3969/j.issn.1674-8115.2017.06.022
    Abstract1414)      PDF(pc) (7473KB)(2928)       Save

     Protein arginine methyltransferase (PRMT) can methylate a variety of proteins, including histones and non-histones, affecting a variety of cellular processes such as transcription, RNA splicing, DNA repair, and cell cycle control. The activity of PRMT is affected by a variety of regulatory mechanisms, and its abnormal expression plays an important role in the development of the diseases, especially in tumors such as breast cancer and leukemia. PRMT has a unique value in the diagnosis or treatment of tumors. With the further exploration of PRMT methylation mechanism, PRMT selective inhibitors have made some progress. PRMT-specific inhibitors are expected to be targeted drugs for the treatment of tumors.

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    Emergence of ciprofloxacin heteroresistance in clinical Pseudomonas aeruginosa
    LI Congcong, YAO Yufeng, ZHANG Chuanzhen
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (7): 839-845.   DOI: 10.3969/j.issn.1674-8115.2022.07.001
    Abstract254)   HTML27)    PDF(pc) (4880KB)(268)       Save
    Objective

    ·To investigate ciprofloxacin heteroresistance in Pseudomonas aeruginosa (PA).

    Methods

    ·Ciprofloxacin heteroresistance in 227 clinical PA strains was initially identified by disk diffusion. Meanwhile, susceptibilities of these strains was classified according to the diameter of the inhibition zone. The stability of the identified heteroresistant strains was tested by measuring the sensitivity after serial passage under antibiotic-free conditions. Mechanisms mediating heteroresistance were analyzed by whole-genome sequencing. Susceptibilities of resistant subpopulations to different antibiotics were also detected.

    Results

    ·Based on disk diffusion, 142 (62.6%), 26 (11.5%), and 59 (26.0%) of 227 isolates were classified as susceptible, intermediate and resistant to ciprofloxacin respectively. Eighteen putative heteroresistant strains were detected through primary disk diffusion selection, and 11 among them were further verified as stable heteroresistant strains by population analysis profiling (PAP). By whole-genome sequencing, 8 and 2 among 11 resistant subpopulations carried mutations in mexS and mutations in gyrA individually. In addition, mutations in fleQ, PA2632 or PAKAF_02255 were detected respectively. Both mexS and gyrA mutants led to moxifloxacin resistance, and some mexS mutants also showed resistance to chloramphenicol and imipenem.

    Conclusion

    ·Ciprofloxacin heteroresistance rate in PA is 4.8% (11/227). As a screening method for heteroresistance of PA, the disk diffusion has low sensitivity and has a certain false negative rate. The mutation mexS is the predominant mutation type in resistant subpopulations and it might enhance the overexpression of efflux pump MexEF-OprN, thus mediating resistance to different antibiotics including ciprofloxacin.

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    Aptamer-drug conjugates (ApDCs): new trend for cancer precision therapy
    HAN Yongqi, HAN Da, XIA Qian, JI Dingkun, TAN Weihong
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (9): 1176-1181.   DOI: 10.3969/j.issn.1674-8115.2022.09.003
    Abstract353)   HTML196)    PDF(pc) (1279KB)(264)       Save

    Cancer is a worldwide medical issue that seriously threatens human health. Precision molecular medicine provides a new strategy for cancer theranostics. As excellent targeting recognition molecules and drug delivery platforms, aptamers and aptamer drug-conjugates (ApDCs) have provided a series of useful molecular tools for cancer precision therapy. In this paper, the properties and the selection techniques of aptamers, the construction of ApDCs and their applications to clinical tumor-targeting therapy are reviewed. Additionally, the challenges and perspective of ApDCs in precision molecular medicine for cancers are presented. This review may provide new horizons for molecular-targeted anti-tumor drugs in the therapy of clinical malignant tumors.

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    Construction of OPEI vector for silencing TRAF6 to promote cartilage regeneration in inflammatory environment
    LIU Hongqiang, LU Yanqing, GAO Yuxuan, WANG Yiyun, WANG Chuandong, ZHANG Xiaoling
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (7): 846-857.   DOI: 10.3969/j.issn.1674-8115.2022.07.002
    Abstract219)   HTML17)    PDF(pc) (6757KB)(228)       Save
    Objective

    ·To construct a low toxicity and high-efficiency joint synovial siRNA transfection vector OPEI, and inhibit tumor necrosis factor receptor-associated factor 6 (TRAF6) to rescue the chondrogenic ability of bone marrow mesenchymal stem cells (BMSCs) under inflammatory conditions.

    Methods

    ·The osteoarthritis (OA) models of SD rats (n=20) were established by medial meniscectomy of knee. Another sham operation group (n=10) was established, and the meniscus remained intact. The cartilage and synovium were collected 3 months after surgery. The expression of TRAF6 was detected by immunohistochemistry, and Western blotting was used to detect the expression of MMP13, TRAF6 and p-p65 in primary rat synovial cells induced by interleukin-1β (IL-1β). Further, the small molecule polyethylenimine (PEI) derivative OPEI was synthesized in anhydrous anaerobic environment, and the ability of OPEI to encapsulate siRNA was detected by agarose gel electrophoresis. The particle size and Zeta potential of OPEI/siRNA complex were measured by dynamic light scattering. The cytotoxicity of the formed complex to rat primary synovial cells was detected by MTT method. The effect of the complex on synovial cell apoptosis was analyzed by flow cytometry. The transfection efficiency of siRNA by OPEI in synovial cells in vivo and in vitro was detected by laser confocal technique and fluorescence microscopy. The proteoglycan content of chondrocyte matrix was detected by alcian blue staining.

    Results

    ·Compared with the sham operation group, TRAF6 was highly expressed in synovium and cartilage of the rat OA models, and inhibition of TRAF6 could significantly reduce the expression of MMP13 and p-p65 in IL-1β-stimulated primary synovial cells. The siRNA transfection efficiency of OPEI in the rat primary synovial cells was as high as 99.33%. A large number of synovial cells ingested siRNA on the 3rd and the 7th day after injection of OPEI / Cy3-siRNA into rat knee joints. Two days after OPEI / siTRAF6 complex with different w/w ratios was transfected into rat primary synovial cells, the results of TRAF6 protein expression showed that the knockout efficiency of TRAF6 gene in the OPEI / siTRAF6 group was 49.05%, 74.61% and 83.18% respectively when the mass ratio was 3∶1, 4∶1 and 5∶1. After TRAF6 gene was silenced by OPEI/siTRAF6, compared with the control group (OPEI/siNC), alcian blue staining of chondrocytes was significantly enhanced under IL-1β stimulation.

    Conclusion

    ·OPEI is a low toxicity and high efficiency siRNA transfection vector, silencing TRAF6 in synovial cells could promote OA cartilage regeneration.

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    New progress and prospects of blood glucose monitoring technology
    JIA Weiping
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (9): 1171-1175.   DOI: 10.3969/j.issn.1674-8115.2022.09.002
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    Glucose monitoring is an important part of diabetes management. For over a century, diabetes monitoring technology has developed from the initial urine glucose test, to the later blood glucose test, and finally to the current continuous glucose monitoring (CGM), which is evolving in a more convenient, accurate, minimally invasive, and even non-invasive direction. CGM refers to the technology that continuously measures glucose concentrations in the subcutaneous interstitial fluid by glucose sensors. It can detect hyperglycemia and hypoglycemia that are not easily recognized by traditional monitoring methods. Using the huge amounts of glucose data generated by CGM technology, diabetes management is expected to be more targeted, with glucose control more accurate. In this context, novel measure of glucose control represented by time in range (TIR) has been popularized, which can provide comprehensive information including hyperglycemia, hypoglycemia, and glucose fluctuation. Hence, the modern approach to glucose control should focus not only on glycosylated hemoglobin, but also pay attention to new metrics such as TIR. In the future, more mature, minimally invasive and even non-invasive glucose monitoring technologies that are comfortable, stable and highly accurate should be further developed to greatly improve the experience and enthusiasm of the patients in blood glucose monitoring. Meanwhile, closed-loop insulin infusion system should be further developed, to truly realize individualized and automated glucose control, as well as further improvement of glucose control in the patients with diabetes.

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    SMAD7 expression in multiple myeloma and its effect on cell proliferation and drug resistance
    DING He, CAO Yanglin, HE Yang, WEI Xing, YANG Jianfeng
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (7): 858-865.   DOI: 10.3969/j.issn.1674-8115.2022.07.003
    Abstract241)   HTML23)    PDF(pc) (2182KB)(208)       Save
    Objective

    ·To analyze the expression of Sma- and Mad-related protein 7 (SMAD7) in multiple myeloma (MM), and its effect on the proliferation and drug resistance of MM cells.

    Methods

    ·Three datasets from the Gene Expression Omnibus (GEO) database were obtained to analyze the differential expression of SMAD7 in healthy donors and MM. Bone marrow samples from 8 healthy donors and 20 MM patients were collected. The relative expression of SMAD7 mRNA in bone marrow CD138+ cells was detected by quantitative real-time PCR (qPCR), and the relationship between SMAD7 mRNA expression and clinical information of patients was analyzed. After overexpression of SMAD7 in MM cells KMS11, the effects of SMAD7 on the proliferation was observed by CCK8 assay and cell cycle assay. KMS11 cells overexpressing SMAD7 were treated with different concentrations of bortezomib, and the effect of SMAD7 on drug resistance and apoptosis of MM cells were observed.

    Results

    ·The analysis of SMAD7 expression data in the datasets showed that compared with healthy donors, SMAD7 expression in MM patients was higher (all P<0.05). The results of qPCR showed that the relative expression of SMAD7 mRNA was up-regulated in MM patients (P=0.002), although no correlation with clinical information of patients was shown. Compared with the control cells, the cell viability of KMS11 was higher after overexpression of SMAD7 (all P<0.05); the change of cell cycle distribution showed that the proportion of cells in S phase decreased (P=0.016), and the proportion of cells in G2/M phase increased (P=0.005); after bortezomib treatment, the drug sensitivity and apoptosis level of overexpression SMAD7 cells was lower.

    Conclusion

    ·The expression of SMAD7 is up-regulated in MM. Overexpression of SMAD7 can promote the proliferation and drug resistance of MM cells.

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    Development of pH-responsive fluorescent probe for tumor microenvironment imaging
    WANG Yuxin, SUN Ruiqi, LIU Jianhua, HE Weina
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (7): 875-884.   DOI: 10.3969/j.issn.1674-8115.2022.07.005
    Abstract243)   HTML17)    PDF(pc) (4327KB)(214)       Save
    Objective

    ·To synthesize a water-soluble pH-responsive near-infrared cyanine-based fluorescent probe, evaluate its optical properties, and conduct in vivo imaging analysis of the quasi-tumor microenvironment.

    Methods

    ·The water-soluble pH-responsive near-infrared fluorescent probe R2S was synthesized via two classic chemical transformation steps and the liposoluble probe R2Z was synthesized in the similar way. 1H nuclear magnetic resonance spectroscopy, mass spectroscopy and high performance liquid chromatography were used to verify the structure and the purity of the probes synthesized. Ultraviolet-visible and photoluminescence spectroscopy were used to evaluate its pH responsiveness, response reversibility and stability. Then, cell permeability of the probe was measured by cell imaging. The cytotoxicity of the probe was evaluated with HCT-116 cells and HeLa cells, and in vivo imaging experiments were performed by using healthy BALB/c female mice. Finally, imaging experiments of quasi-tumor-acidic-microenvironment were carried out by separately injecting PBS solution with pH 6.50 and pH 7.40 into the back of the mice, and the fluorescence intensity of R2S at pH 6.50 and pH 7.40 was compared.

    Results

    ·The water-soluble pH-responsive near-infrared fluorescent probe R2S and its liposoluble analog R2Z were synthesized successfully. As the acidity of the probe solution increased (from pH 11.10 to pH 3.47), the maximum absorption wavelength of R2S shifted from 642 nm to 774 nm, while the maximum emission wavelength shifted from 794 nm to 808 nm, with a pKa value of 6.88. Compared to the liposoluble probe R2Z, R2S showed a larger Stokes shift, higher stability without affecting the cell membrane permeability. At the high administration concentration of 100 μmol/L, R2S did not exhibit the inhibition of proliferation, while for R2Z at the concentration of 12.5 μmol/L, the relative cell viability already descended to below 80%, indicating R2S had higher biosecurity than R2Z. Imaging of R2S in low pH tissue (simulating tumor tissue) and normal pH tissue exhibited a high degree of discrimination.

    Conclusion

    ·The water-soluble pH-responsive near-infrared cyanine fluorescent probe R2S exhibits sensitive and stable responses to pH changes, and the optimal response range is consistent with the pH of the tumor acidic microenvironment, illustrating a strong potential for its in vivo tumor imaging applications.

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    Facing the trends of “Double First-Class” initiative, enhancing the construction of top disciplines: some thoughts on the construction of oral and maxillofacial surgery in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine
    QIU Weiliu
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (9): 1163-1170.   DOI: 10.3969/j.issn.1674-8115.2022.09.001
    Abstract303)   HTML200)    PDF(pc) (7021KB)(128)       Save

    The core of “Double First-Class” initiative is discipline construction. Through reviewing the development and the achievements of the Department of Oral and Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, and two guiding thoughts, i.e., “high ambition” and “reform and opening up”, the following four experiences are summarized: talent cultivation and echelon construction, talent diversion to increase spillover effect, advocating interdisciplinarity and transdisciplinarity, and introducing system reform and discipline innovation. Furthermore, four suggestions for the future are proposed: the oral and maxillofacial surgery of “Chinese style” should be changed to “Chinese characteristics”; innovation should be taken as the forerunner and scientific research as the soul; with the integration of natural science and humanities as the breakthrough point and the guidance of integration, the interdisciplinary talents should be trained; humanistic education in medicine should be further enhanced.

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    Levels of adiponectin in the peripheral blood of patients with immune thrombocytopenia and its effect on the differentiation of megakaryocyte cell line
    LI Xinyu, ZUO Bin, WANG Wen, NIU Xiaoyin, WENG Zhen, HE Yang
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (7): 866-874.   DOI: 10.3969/j.issn.1674-8115.2022.07.004
    Abstract197)   HTML16)    PDF(pc) (2387KB)(210)       Save
    Objective

    ·To explore the level of adiponectin in the peripheral blood plasma of patients with immune thrombocytopenia (ITP) and its effect on the differentiation and maturation of megakaryocytes.

    Methods

    ·From January 2021 to February 2022, the peripheral blood samples were collected from 46 ITP patients in the Department of Hematology, The First Affiliated Hospital of Soochow University and 30 healthy controls with corresponding gender and age in the physical examination center. The plasma adiponectin levels in the ITP patients and healthy control (HC) group were detected by using human adiponectin enzyme-linked immunosorbent assay (ELISA) kits. And the correlation between adiponectin level and body mass index (BMI) in the ITP patients was analyzed. In terms of cell experiments, real-time quantitative PCR (RT-qPCR) and Western blotting were used to study the expression of adiponectin receptors (ADIPOR1 and ADIPOR2) in the myeloid cell line K562, and the megakaryocyte cell lines MEG-01 and Dami at mRNA and protein levels, respectively. The differentiation of K562 cell line and the maturation of MEG-01 and Dami cell lines were induced by phorbol 12-myristate 13-acetate (PMA). At the same time, the cells were treated with different concentrations of adiponectin receptor agonist AdipoRon. Flow cytometry was used to detect the percentage of CD41+ cells, the mean fluorescence intensity (MFI) of CD41, and the proportion of polyploid cells (≥4N).

    Results

    ·Compared with the HC group, the plasma adiponectin level of the ITP patients significantly increased (P=0.000), and there was no significant correlation between the adiponectin level and the BMI of the patients (P=0.621). RT-qPCR and Western blotting showed that ADIPOR1 and ADIPOR2 were expressed in K562, MEG-01 and Dami cell lines. The proportion of CD41+ cells in the K562 cell line co-cultured with 10 μmol/L or 20 μmol/L AdipoRon and PMA for 72 h were significantly lower than those in the PMA+DMSO group (P=0.000). The CD41-MFI (P=0.047) and the proportion of polyploid cells (P=0.003) in the MEG-01 cell line co-cultured with 20 μmol/L AdipoRon and PMA for 72 h were significantly higher than those in the PMA+DMSO group; however, in the Dami cell line, no significant increases of both were found after the treatment of 20 μmol/L AdipoRon and PMA.

    Conclusion

    ·The adiponectin level is elevated in the peripheral blood plasma of ITP patients. Human myeloid cell line K562, and megakaryocyte cell lines MEG-01 and Dami all express adiponectin receptors ADIPOR1 and ADIPOR2. Adiponectin receptor agonists can inhibit megakaryocyte differentiation in vitro, but its effect on megakaryocyte maturation is uncertain.

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    Comparison analysis of researches on mental health of university students in China and abroad
    LU Wei, ZHAO Min
       2012, 32 (10): 1382-.   DOI: 10.3969/j.issn.1674-8115.2012.10.023
    Abstract3969)      PDF(pc) (404KB)(2257)       Save

    The research on mental health of university students has been developing rapidly in China in recent years, but it still significantly lags behind that of the developed countries. Through analysis of related domestic and overseas literatures, the status of mental health and research method of mental health of university students in China are summarized, and are compared with those of the other countries in this paper. It is suggested that the team building, methodology, horizon and range of research on mental health of university students should be strengthened in China.

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    Effect of transient receptor potential vanilloid 4 on traumatic heterotopic ossification around temporomandibular joint
    ZHU Yue, GU Jiaying, DAI Jiewen
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (12): 1649-1655.   DOI: 10.3969/j.issn.1674-8115.2022.12.001
    Abstract217)   HTML47)    PDF(pc) (3467KB)(144)       Save

    Objective ·To investigate the effect of transient receptor potential vanilloid 4 (TRPV4) on traumatic heterotopic ossification around temporomandibular joint (THO-TMJ). Methods ·Eighteen eight-week-old male mice were divided into two groups by simple random sampling. Half right condylar cartilage was removed in every mouse. Nine mice in experimental group was administered TRPV4 blocker [14 mg/(kg·d)] via oral gavage. The same amount of saline was given to nine mice in control group. The skull samples were collected at 14, 30 and 90 d after surgery. The heterotopic ossification was evaluated by H-E staining and Micro CT scan. Three-dimensional reconstruction of the skulls was performed to measure the volume and surface area of condyles. Morphometric index (MI) was applied to indicate the degree of heterotopic ossification in both groups. Results ·H-E staining results showed that active endochondral ossification occurred around the injured condyles in both groups. Micro CT images showed that the tissue density around the condyles in both groups gradually increased in the TMJ area after operation, and then the ectopic bone tissues gradually proliferated outside the condyle, partially connecting to the joint fossa. Scattered osteophytes were seen in the joint space. The trend of TMJ bone fusion was more obvious in the control group. The morphological index of the experimental group (MI=0.15±0.01) was lower than that of the control group (MI=0.18±0.03, P<0.05). Conclusion ·Blocking TRPV4 function can help reduce the formation and progression of THO-TMJ.

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    Research progress and clinical intervention strategy of age-related hearing loss
    HUANG Zhiwu, WU Hao
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (9): 1182-1187.   DOI: 10.3969/j.issn.1674-8115.2022.09.004
    Abstract253)   HTML36)    PDF(pc) (1903KB)(139)       Save

    Age-related hearing loss (ARHL), also known as presbycusis, has not been paid enough attention to worldwide due to the lack of awareness of its harmfulness for a long time. In the past decade, with the increase of aging and related social problems, ARHL has attracted more and more attention from government and society, and its pathological mechanism and clinical intervention research have also developed rapidly. However, it is still unclear about the pathogenic mechanism of ARHL caused by genetic and environmental factors. This review briefly introduces the basic pathological characteristics of ARHL, and summarizes the related researches on its genetic and environmental (especially noise exposure) pathogenic mechanism and clinical intervention effect, as well as the research progress of the writers' research group in this field, which is expected to help government promote and formulate relevant interventions and medical policies on the hearing health in the elderly.

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    Immune inhibitory receptor LILRB2 enhances SARS-CoV-2 spike protein-mediated immune inflammation
    YANG Wenqian, CHEN Chiqi, ZHAO Lu, CAO Liyuan, XIA Yiqiu, LU Zhigang, ZHENG Junke
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (9): 1188-1196.   DOI: 10.3969/j.issn.1674-8115.2022.09.005
    Abstract283)   HTML33)    PDF(pc) (2295KB)(133)       Save

    Objective ·To explore the possible roles of immune inhibitory receptor leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2) in the immune inflammation after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and provide a potential therapeutic way for the coronavirus disease 2019 (COVID-19). Methods ·The supernatants containing the extracellular domain of spike protein (S-ECD) were collected, and the detection of the protein expression and activity in the conditional medium by Western blotting and flow cytometric analysis was followed by. The binding of S-ECD with LILRB2 was measured by co-immunoprecipitation and flow cytometric analysis. The mRNA expression levels of several inflammation genes in a human mononuclear cell line (THP1) or peripheral blood mononuclear cells (PBMC) were measured after spike protein stimulation for 24 h by quantitative RT-PCR. The protein levels of interleukin-6 (IL-6) and interleukin-1β (IL-1β) in the conditional medium were examined by enzyme-linked immunosorbent assay (ELISA). The siLILRB2 was transferred into CD33+ myeloid cells purified from human peripheral blood with Lipofectamine 3000 reagents. The knockdown efficiency was detected 24 h after transfection by flow cytometric analysis. The difference in the protein levels of IL-6 between the control cells and LILRB2-knocked-down cells after spike protein treatment was evaluated by ELISA. Results ·The study established a transfection system with 293T cells by which the SARS-CoV-2 S-ECD could be secreted to supernatants with normal biological activities. The interaction and the binding of spike protein with LILRB2 were evaluated by a co-immunoprecipitation assay and flow cytometric analysis, respectively. The mRNA expression levels of IL-6, IL-8, arginase 1 and IL-2 in THP1 cells were significantly up-regulated 24 h after spike protein treatment compared to the control cells (all P<0.05). Consistently, the mRNA levels of IL-6, transforming growth factor-β (TGF-β), IL-8, IL-10 and IL-1β in PBMC were notably increased after spike protein stimulation (all P<0.05). In addition, spike protein could also induce the release of IL-6 and IL-1β in PBMC as measured by ELISA (all P<0.05). More importantly, spike protein was able to increase the secretion of IL-1β and IL-6 by CD33+ myeloid cells 24 h after treatment (both P<0.05). LILRB2-overexpressing THP1 cells produced more IL-6 24 h after treatment with spike protein than the control cells (P<0.05). Two siRNAs could efficiently down-regulate the expression of LILRB2 in CD33+ cells as evaluated by flow cytometric analysis. Consistently, spike protein had no effect on the IL-6 secretion to supernatant from LILRB2-knockdown CD33+ myeloid cells. Conclusion ·SARS-CoV-2 can induce cytokine release syndrome by inflammatory factors, such as IL-6 and IL-1β, released by myeloid cells through spike protein binding to LILRB2.

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    Correlation of WD 40 repeat 43 expression in lung adenocarcinoma and its effect on paclitaxel-resistance of cells
    ZHAO Xue, DONG Chunyan
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (12): 1656-1665.   DOI: 10.3969/j.issn.1674-8115.2022.12.002
    Abstract170)   HTML33)    PDF(pc) (7229KB)(106)       Save

    Objective ·To investigate the expression of WD 40 repeat protein 43 (WDR43) mRNA in lung adenocarcinoma (LUAD) cells and its correlation with the prognosis of LUAD patients, and analyze the effect of WDR43 on the paclitaxel-resistance of LUAD cells. Methods ·Cancer Therapeutics Response Portal (CTRP) was used to download the correlation coefficient between gene expression and paclitaxel sensitivity of LUAD cells, and the paclitaxel resistance-associated genes were screened. Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis were used to analyze the paclitaxel resistance-associated genes, and WDR43 gene was chosen to perform further study. Human Protein Atlas (HPA) database was used to explore the expression and location of WDR43 protein in LUAD tissues. The cancer genome atlas (TCGA) database was retrieved to analyze the difference of WDR43 mRNA expression in LUAD tissues and normal lung tissues, the mutation of WDR43 in LUAD patients, and the correlation between WDR43 mRNA and clinicopathological factors. CaArray database was used to analyze the relationship between WDR43 mRNA and the prognosis of LUAD patients. Tumor Immune Estimation Resource (TIMER) was used to analyze the relationship between WDR43 expression and the infiltration level of immune cells in LUAD tissues. The expressions of WDR43 gene in LUAD cell lines were analyzed by Cancer Cell Line Encyclopedia (CCLE) database, the WDR43 differential-expressed LUAD cells were constructed and the effect of WDR43 expression on paclitaxel resistance was validated by MTT assay and plate colony formation assay. Results ·WDR43, a paclitaxel sensitivity-related gene, was selected by CTRP. The results of GO function analysis and KEGG pathway analysis showed that WDR43 and other genes were associated with rRNA processing and regulation of cell shape, and were enriched on the pathway such as herpes simplex virus 1 infection and cytosolic DNA-sensing pathway. The analysis results of HPA database showed that WDR43 protein was mainly expressed in the cellular nucleus, cellular cytoplasm and cellular membrane of LUAD tissues. The analysis results of TCGA database showed that the expression of WDR43 mRNA in LUAD tissues was higher than that in normal lung tissues (P=0.000), the expression in cancer tissues of LUAD smokers was higher than that of non-smokers (P=0.000), and the expression in TP53 mutant patients was also higher than that in TP53 wild-type patients (P=0.000). The analysis results of CaArray database showed that LUAD patients with WDR43 mRNA-high expression had poor prognosis (both P=0.000). The analysis results of TIMER database showed that the expression of WDR43 could promote the infiltration level of neutrophils, CD8+ T cells, myeloid-derived suppressor cells and macrophages, and inhibit the infiltration level of CD4+ T cells in LUAD tissues. In vitro experiments confirmed that overexpression of WDR43 could enhance the drug resistance of LUAD cells to paclitaxel. Conclusion ·The expression of WDR43 in LUAD tissues is significantly increased and negatively correlated with the prognosis of patients. Overexpression of WDR43 could enhance the paclitaxel resistance of LUAD cells.

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