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    Protocols for diagnosis and treatment of temporomandibular joint osteoarthritis: experience from the TMJ Center of Shanghai Ninth People 's Hospital, Shanghai Jiao Tong University School of Medicine
    ZHANG Shanyong, YANG Chi
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (6): 709-716.   DOI: 10.3969/j.issn.1674-8115.2022.06.003
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    Temporomandibular joint osteoarthritis (TMJOA) is the most common degenerative disease in the temporomandibular joint, mainly manifesting with pain in the joints and the muscles, joint locking, popping, crepitus, and limited mouth opening, which may undermine the quality of patients' life. The main pathological features of TMJOA include chronic synovitis, progressive articular cartilage degeneration, and abnormal subchondral bone remodeling. At present, its pathogenesis is still unclear, and abnormal mechanical load, trauma, heredity, metabolism, gender and age can all be regarded as pathogenic factors. Commonly used diagnostic methods for TMJOA include magnetic resonance imaging (MRI) and computed tomography [(CT/cone beam CT (CBCT)]. The staging standards of TMJOA mainly include Wilkes staging system and Yang's staging system. The clinical treatment of TMJOA mainly includes two categories: non-surgical treatment and surgical treatment. Non-surgical treatment includes health education, psychological consultation, medication, occlusion treatment, etc. Surgical treatment includes arthrocentesis, arthroscopic surgery, disc anchoring, autogenous tissue graft, and total joint replacement. This paper summarizes the diagnosis, staging, surgical treatment and postoperative evaluation of TMJOA on the basis of literature review, and proposes diagnosis and treatment protocols based on the experience of the TMJ Center of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, so as to provide reference for clinicians.

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    Research progress in the role and mechanism of lactylation in diseases
    GE Lingling, HUANG Hongjun, LUO Yan
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (3): 374-379.   DOI: 10.3969/j.issn.1674-8115.2023.03.014
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    Lactic acid is a product of cell respiration. After entering into cells, glucose is metabolized to pyruvate by glycolysis. When the oxygen supply is sufficient, pyruvate is converted to acetyl coenzyme A through pyruvate dehydrogenase in the mitochondrial matrix to participate in the tricarboxylic acid cycle and provide necessary energy for cells. Pyruvate is catalysed by lactate dehydrogenase in the cytoplasm to produce lactate while cells are grown under hypoxic conditions. Lactate not only provides energy for mitochondrial respiration, but also plays important roles in inflammatory responser, wound repair, memory formation and neuroprotection as well as tumor growth and metastasis and other pathophysiological processes through autocrine, paracrine, and endocrine forms, which affects the development and prognosis of diseases. Epigenetic modification regulates gene replication, transcription and translation by covalently adding or hydrolyzing functional groups on histones and DNA through related enzymes and affects the biological effects of cells. Histones are the major structural proteins of eukaryotic chromosomes. Their post-translational modifications, such as methylation and acetylation, affect their affinity with DNA, change chromatin structures, and are widely involved in regulation of gene expression. Recent studies have found that histones can undergo lactylation, which is a new epigenetic modification by adding lactate to lysine residues on histones. As the research deepens, numerous evidences reveal that lactylation also occurs on non-histone proteins. The discovery of lactylation has expanded our understanding of lactate functions in the pathogenesis of diseases. In this review, we summarize the roles and mechanisms of lactylation in tumor, inflammatory and neural system diseases, in order to provide new ideas for the research, diagnosis and treatment of these diseases.

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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
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    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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    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
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    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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    Progress in metabolism of the immune cells in tumor microenvironment
    LIN Jiayu, QIN Jiejie, JIANG Lingxi
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (8): 1122-1130.   DOI: 10.3969/j.issn.1674-8115.2022.08.018
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    Metabolic reprogramming refers to cells' mechanism to change their metabolic patterns in order to meet the increased energy demand caused by growth and proliferation. By way of metabolic reprogramming such as the Warburg effect, tumor cells gain rich energy to support their own survival, growth, and metastasis. The tumor microenvironment (TME) is the internal environment in which tumor cells survive, containing not only tumor cells, but also stromal cells, immune cells, and other components that are closely related to tumor cells. Meanwhile, tumor cells regulate intercellular function and signaling via secreting cytokines, metabolites, and other molecules and shape a commonly hypoxic, acidic, and nutrient-deprived TME which contributes the most to immune resistance. However, rapidly proliferating tumor cells compete for relatively scarce nutrients with immune cells, consequently, producing an immunosuppressive metabolism microenvironment. Under the influence of immunosuppressive TME, immune cells generate tolerance phenotype-related metabolic adaptations through metabolic reprogramming to satisfy their own needs and further perform anti-tumor or immunosuppressive roles. The response of immune cells to tumor cells mainly depends on respective unique metabolic pathways, which are related to the type and function of immune cells. Moreover, the functional properties of immune cells are directly associated with the immunotherapy effects. Regulating metabolic pathways of immune cells provides a great direction for cancer therapy. In this paper, the main metabolic pathways of immune cells in TME is described, the relationship between their metabolic characteristics and immune functions is summarized, and the mechanism of metabolic pathways underlying the functions of immune cells is further discussed, providing new insights for unveiling tumor immunosuppressive microenvironment and improving the efficacy of tumor immunotherapy.

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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
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    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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    Application of a tent-pole screw technology in reconstruction of severe alveolar bone defect: a retrospective study of 30 patients
    WU Jing, ZHAO Zhengyi, ZOU Duohong, YANG Chi, ZHANG Zhiyuan
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (6): 768-777.   DOI: 10.3969/j.issn.1674-8115.2022.06.011
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    Objective

    ·To explore the effect of a tent-pole screw technology on reconstruction of severe alveolar bone defect.

    Methods

    ·Thirty patients underwent tent-pole screw technology to reconstruct severe alveolar bone defects in the Department of Stomatology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2018 to January 2021 were enrolled. By analyzing and reconstructing the image data of cone-beam computed tomography (CBCT) before and 8 months after operation, the effects of repairing and reconstructing the horizontal, vertical and mixed alveolar bone defects were counted. The alveolar bone volumetric parameters were evaluated by micro-computed tomography (Micro-CT), and trabecular bone number (Tb. N), trabecular bone thickness (Tb. Th), bone volume/total volume (BV/TV) and bone mineral density (BMD) were calculated to assess the maturity of regenerated bone. The regeneration of alveolar bone and remanent scaffold were calculated by analyzing histological sections.

    Results

    ·Eight months after using the tent-pole screw, the vertical bone gain value was 4.81 (1.58, 7.66) mm, and the horizontal post-operative width was 3.96 (2.38, 5.67) mm. Additionally, the bone volume gain was 2 157.22 (776.59, 2 831.63) mm3. Micro-CT analysis of bone core, which was collected 8 months after the surgery, and Tb. N was (3.09±0.68)/mm, Tb. Th was (0.08±0.01) μm, BV/TV was (25.24±5.60)% and BMD was (0.24±0.05) g/cm3. Histological sections showed that the percentages of regenerated bone and remanent scaffold were (16.30±3.57)% and 34% (31.75%, 38.25%), respectively. These data suggested good new bone formation in targeted area. There were no complications or adverse events during surgery or post-operative healing.

    Conclusions

    ·Based on “stability-oriented” alveolar ridge augmentation, using tent-pole screw, membrane pins and packaging structure in a standard operation procedure can achieve beneficial results for bone augmentation, while complications seldom occurre. The tent-pole screw may offer predictable and exceptional outcomes for implantation site preparation, especially for large alveolar defects, which will provide advantages to subsequent implantation and restoration.

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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
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    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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    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
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    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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    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
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    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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    Research progress of clinical application of ASPECT score in acute ischemic stroke
    WEI Xuemin, GAO Chengjin
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (7): 919-924.   DOI: 10.3969/j.issn.1674-8115.2022.07.011
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    Acute ischemic stroke (AIS) is characterized by a high rate of disability and mortality, and rapid and accurate diagnosis and appropriate treatment are the keys. The severity of AIS patients depends on the location of early ischemic changes (EIC) in the brain tissue and the size of the lesion, so it is necessary to evaluate the patients' conditions by combining with imaging. The Alberta stroke program early CT score (ASPECT score) is a 10-point imaging score system that evaluates the EIC in the middle cerebral artery supplying region of the stroke patients in an accurate and simple way by quantifying the severity in terms of the imaging to help clinicians make medical decisions. ASPECT score is not only widely used to predict the prognosis of stroke patients, but also to identify the population benefiting from the endovascular therapy and evaluate the risk of endovascular therapy for patients. ASPECT score combined with multimodal imaging has also been used to predict ischemic core volumes and the prognosis. In recent years, with the development of artificial intelligence, automatic ASPECT scoring methods based on machine learning have emerged. This paper reviews ASPECT scoring methods, its value in the treatment and the assessment of prognosis in AIS, multimodal ASPECT scoring, and the application of automated ASPECT scoring combined with artificial intelligence.

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    MicroRNA-30b-5p inhibits autophagy in ovarian granulosa cells in polycystic ovary syndrome rats by targeting Atg5
    WANG Xuemin, WANG Yanan, NIU Aiqin, YE Ying, LI Fei
    Journal of Shanghai Jiao Tong University (Medical Science)   
    Online available: 18 January 2023

    Diagnosis and treatment protocol of temporomandibular joint (TMJ) ankylosis: experience from the TMJ Center of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine
    HE Dongmei, YANG Chi
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (6): 702-708.   DOI: 10.3969/j.issn.1674-8115.2022.06.002
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    Temporomandibular joint (TMJ) ankylosis is characterized by limited mouth opening, facial deformity when it happened during growth and obstructive sleep apnea. It is a refractory disease which will seriously affect the mandibular function and facial appearance of the patients. With the development of new technology and accumulating experience, the treatment results have been significantly improved. Based on the literature review, this paper concludes the surgical treatment experience from the TMJ Center of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, so as to provide reference for clinicians. In the imaging diagnosis of TMJ ankylosis, CT coronal reconstruction is fundamental for the classification of TMJ ankylosis. It can be divided into four types according to the presence and size of residual condyle structure on the medial side of the bony fusion. In addition, jaw deformities, occlusal relationship disorders and respiratory structural disorders associated with TMJ ankylosis can be further classified. Surgical treatment of TMJ ankylosis includes lateral gap arthroplasty (LAP) and joint reconstruction. When there is a condylar structure medially to the bony fusion, which is greater than or equal to 1/2 of the internal and external diameter of the normal condyle, LAP is selected to preserve the condyle and joint disc structure; other types of joint reconstruction include autogenous bone transplantation, artificial joint reconstruction, distraction osteogenesis, etc. Orthognathic surgery can be performed simultaneously or in the second stage to correct combined jaw deformities. Autologous fat transplantation can significantly reduce the recurrence of TMJ ankylosis.

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    Reflection and exploration of digital chronic disease management based on the proactive health index
    GAO Xiang, LI Xiaoguang, ZHOU Liang, WANG Hui
    Journal of Shanghai Jiao Tong University (Medical Science)    2023, 43 (2): 137-142.   DOI: 10.3969/j.issn.1674-8115.2023.02.001
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    The disease burden caused by chronic non-communicable diseases continues to grow, with profound implications for public health and socio-economic development. The traditional health management of chronic diseases lacks diagnostic criteria and reasonable intervention time, and the bottleneck of the lack of residents' initiative is increasingly prominent. The construction of proactive health index (PHI) is expected to be an effective means to improve the health management of chronic diseases. As the world enters a critical period of digital transformation, China's health strategy has made clear that technological innovation and information technology should play a leading role in maintaining people's health, and digital health brings strategic opportunities for the development of chronic disease health management. In the context of the development of digital chronic disease prevention and control, this study analyzes the main bottlenecks existing in China's chronic disease health management, clarifies the importance of establishing diagnostic criteria for chronic disease health management, proposes the concept of PHI, and introduces the construction of PHI to solve the key problems of chronic disease health management. The application scenarios of PHI are deployed and prospected from the government side, the family physician side and the public side, in order to provide ideas for improving residents' health management initiative and enhancing the effectiveness of chronic disease health management.

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    Progress of interoception based on heartbeat perception
    LIANG Yuxuan, LI Chunbo
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (5): 660-666.   DOI: 10.3969/j.issn.1674-8115.2022.05.015
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    In some early classical emotional theories, psychologist JAMES has proposed that emotions are the perception of physiological changes in the body, i.e., physiological changes (such as rapid heartbeat) occur before emotions such as fear and tension. Later, researchers defined the human body's ability to perceive internal physiological signals (such as heartbeat, breathing and gastrointestinal peristalsis) as interoception, in which behavioral evaluation of heartbeat perception has received extensive attention. At present, it is generally accepted that interoception can be measured in three dimensions, i.e., accuracy, sensitivity and awareness. Several studies have shown that interoception is highly correlated with the intensity of emotional experience, and the changes in interoception can also be observed in the clinical groups suffering from anxiety disorder, depression disorder, schizophrenia and other mental disorders. Using functional magnetic resonance imaging and other techniques, the researchers has found that the insula may be the center of interoception, which overlaps with the active brain regions of emotional experience, providing the neuroanatomical evidence for the emotional theory. Recently, more and more studies focus on the field of interoception, but the published domestic reviews mostly concentrated on psychology without connection with clinical practice. Therefore, this paper comprehensively reviews the interoceptive dimensions, measurement methods, research techniques and clinical researches based on heartbeat perception, and prospects the research directions of interoception.

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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
    Abstract421)   HTML22)    PDF(pc) (4327KB)(394)       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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    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
    Abstract577)   HTML211)    PDF(pc) (1658KB)(370)       Save

    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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    Progress in mechanism of transcranial direct current stimulatio
    WANG Yang, CHENG Jiayue, WANG Zhen
    Journal of Shanghai Jiao Tong University (Medical Science)   
    Online available: 25 July 2022

    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
    Abstract440)   HTML51)    PDF(pc) (1903KB)(365)       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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