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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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    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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    Current situation, problems and directions of high-risk pregnancy research in China
    LIN Yi
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (4): 403-408.   DOI: 10.3969/j.issn.1674-8115.2022.04.001
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    With the progressive initiation of the two- and three-child policy in China, and under the influence of various factors in society, the proportion of high-risk pregnancy has increased, especially those linked to advanced age conception (more than 35 years old). In pathological pregnancy, the incidence of recurrent miscarriage and preterm birth remains high. The diagnosis and treatment of common pregnancy complications such as preeclampsia and eclampsia are lagging behind. Diseases that cause maternal death have changed. The cases of deep vein thrombosis causing maternal deaths have increased. Expanding floating population increases the risk of adverse pregnancy outcomes. The widespread use of assisted reproduction has led to high risk of adverse pregnancy outcomes. The increase in the number of elder mothers has led to high risk in fetal birth defects. All of these have led to a new challenge in terms of maternal safety and care, urging scientists and clinicians to establish a more accurate risk assessment standard for pregnant women, especially for the elderly pregnant women, implement whole pregnancy management and standardized diagnosis and treatment, standardize the treatment for abortion, and establish a triple monitoring system for identifying maternal arterial rhythm, maternal heart rate and fetal heart rate. Finally, a hospital-home monitoring and warning system will be set up based on the Internet of things and information automation. This paper describes the current status, problems and directions of high-risk pregnancy research under the background of the new population policy, and provides new strategies for the protection of maternal and child health.

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    Diagnosis and treatment protocol of mandibular condylar fracture: 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): 695-701.   DOI: 10.3969/j.issn.1674-8115.2022.06.001
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    Mandibular condylar fracture is common in clinic. Improper treatment will cause sequelae such as malocclusion, ankylosis and limited mandibular development. This paper combines the literature review and the diagnosis and treatment experience of the team to provide reference for clinicians. Imaging diagnosis, especially coronal CT reconstruction, is the basis for classification and treatment of condylar fracture. According to the fracture location, it is divided into condylar (intracapsular) fracture, condylar neck fracture and subcondylar fracture. And intracapsular fracture can be further divided into four types: A, B, C and M. The treatment of condylar fracture includes non-surgical treatment and surgical treatment. For non-surgical treatment, intermaxillary elastic traction is recommended for malocclusion correction. The absolute indication of surgical treatment is the ramus stump dislocated out of the fossa. The relative indications include the stump of the mandibular ramus contacting the articular fossa, severe displacement or dislocation of the condylar neck and subcondylar fracture. The key points of successful operation include adequate exposure, anatomic reduction and stable fixation, protection of lateral pterygoid muscle attachment and articular cartilage, and reposition of the temporomandibular joint disc. For the condylar fracture combined with mandibular fracture, lingual fissure of the mandible should be closed during reduction and fixation for restoring the mandibular width and condylar position in the fossa. When the condylar fracture is combined with midface fracture, the condylar fracture and occlusal relationship should be restored first, and then the maxillary fracture should be fixed according to the lower dentition. The children under 6 years old have the stronge ability of condylar remodeling, so non-surgical treatment is commonly used. The healing and remodeling ability of condyle gradually decreases with age. The condyles of the teenagers over 12 years old are close to those of the adults, so the indications of surgical treatment for condyle fracture refer to the adults.

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    Different roles of SMAD2 and SMAD3 in human embryonic stem cell differentiation
    ZHAO Bingnan, MA Shuangyu, XU Chunlong, WANG Qiong
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (4): 443-454.   DOI: 10.3969/j.issn.1674-8115.2022.04.006
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    Objective

    ·To investigate the different roles of SMAD proteins (drosophila mothers against decapentaplegic proteins)—SMAD2 and SMAD3, the major downstream effectors of the transforming growth factor β (TGFβ) family, in the differentiation process of human embryonic stem cells (hESCs) in vitro.

    Methods

    ·The protein levels of SMAD2 and SMAD3 were measured by Western blotting in hESCs. The SMAD2 knockout (SMAD2KO) and SMAD3 knockout (SMAD3KO) cell lines were constructed in hESCs by CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) technology. Immunofluorescence staining was used to detect the effect of SMAD protein loss on the expression of pluripotent factors octamer-binding transcription factor 4 (OCT4) and sex determining region Y-box 2 (SOX2), neuroectoderm (NE) factors paired box 6 (PAX6) and sex determining region Y-box 1 (SOX1), and mesendoderm (ME) factor SOX17. Flow cytometry was used to identify the expression changes of NE factor PAX6 and ME factor SOX17, eomesodermin (EOMES) and C-X-C motif chemokine receptor 4 (CXCR4) upon SMAD2 or SMAD3 loss. SMAD2 and SMAD3 plasmids were overexpressed in SMAD2KO and SMAD3KO cell lines, respectively, which were verified by Western blotting. Real-time quantitative reverse transcription PCR (qRT-PCR) was used to check whether the recoveries of SMAD proteins in SMADKO cell lines could restore the expression of ME key factors, like EOMES, forkhead box A2 (FOXA2) and goosecoid homeobox (GSC) during differentiation.

    Results

    ·Although the protein sequences of SMAD2 and SMAD3 were similar, SMAD2 was the main factor expressed in hESCs. SMAD2 knockout and SMAD3 knockout did not affect the expression of pluripotent factors OCT4 and SOX2 from immunofluorescence staining results, nor the expression of NE factors PAX6 and SOX1 combined with flow cytometry results. SMAD3 knockout had no significant effect on the differentiation of hESCs into ME, while SMAD2 knockout severely hindered the expression of ME specific factors such as SOX17, EOMES and CXCR4. By qRT-PCR analysis, overexpression of exogenous SMAD2 in SMAD2KO cells can effectively restore the expression of ME genes including EOMES, FOXA2 and GSC, while replenishment of SMAD3 in SMAD3KO cells almost had no effect.

    Conclusion

    ·SMAD2 and SMAD3 play different roles in the ME differentiation of hESCs. SMAD2, but not SMAD3, is critical for the expression of ME genes in hESCs.

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    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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    Summary of clinical research of Pediococcus pentosaceus in treatment of infantile colic
    WU Shiyin, CAI Meiqin
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (11): 1633-1637.   DOI: 10.3969/j.issn.1674-8115.2022.11.017
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    Infantile colic is a common disease. Its etiology is not clear, which may be related to the imbalance of intestinal flora. Pediococcus pentosaceus is a probiotic of Pediococcus of Lactobacillaceae. It can enhance host immunity and improve the diversity of intestinal flora. This paper will introduce the characteristics of probiotics such as antibacterial capability, intestinal colonization ability and antibiotic sensitivity of Pediococcus pentosaceus, and the probiotic functions such as antioxidant, antiviral and immune regulation, and elaborate on the possible pathogenesis of infantile colic, the efficacy and potential mechanism of Pediococcus pentosaceus in the treatment of infantile colic, and the current situation of clinical research at home and abroad, in order to provide a scientific basis for Pediococcus pentosaceus in the treatment of infantile colic.

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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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    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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    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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    Adaptation and adaptability investigation of Improving Parents as Communication Teachers (ImPACT) program for autism spectrum disorder
    WU Danping, REN Fang, SHEN Lixiao, XUE Minbo, WANG Junli, LI Fei, XU Mingyu
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (9): 1239-1246.   DOI: 10.3969/j.issn.1674-8115.2022.09.010
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    Objective ·To adapt and investigate the adaptability of the parent-mediated intervention program “Improving Parents as Communication Teachers (ImPACT)” for autism spectrum disorder (ASD) under the background of Chinese culture. Methods ·There were 4 procedures of adaptation: information gathering, preliminary adaptation design, preliminary adaptation test, and adaptation refinement. In the information collection part, 8 experts (6 pediatrics and 2 psychotherapists) were invited to have 6 focus group discussions, and preliminary adaptation was made in the aspects of language, intervention form, program structure, cultural customs, etc., according to expert suggestions. Then 16 ASD parents were recruited to participate in the ImPACT program after the preliminary adaptation. Adaptative investigation of ImPACT was carried out simultaneously in the preliminary adaptation test stage. Results ·The adaptability investigation results of preliminary adaptation program showed that all parents believed that “the pace of the program was well controlled, and they could follow the rhythm of the therapist to complete the learning of skills”. Among these parents, 66.67% believed that “the course was fully prepared, the explanation was clear, and the goal was clear”, and 33.34% believed that “rich examples were provided to help understand intervention skills” in the learning process. As for the feedback of skill practice homework after each session, 83.33% of parents believed that “homework could be easily completed, and help them better learn intervention skills”, and all parents believed that “comments were timely, and the content of comments could help them answer questions and solve doubts”. The difficulties in mastering, i.e., the 7th session (shaping the interaction), the 6th session (teaching new imitation and play skills), and the 5th session (teaching new communication skills) were further adjusted after discussion with the expert group to make the final plan more convenient for parents to master. Conclusion ·After adaptation and adaptability investigation, a parent-mediated intervention program ImPACT which is more suitable for the families of ASD children in China has been formed.

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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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    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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    Establishment and application of an in vitro detection method for antibody gene point mutation, insertion and deletion
    LUO Simin, YEAP Lengsiew, HAO Qian
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (4): 518-527.   DOI: 10.3969/j.issn.1674-8115.2022.04.015
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    Objective

    ·To establish an in vitro method for rapidly detecting mutations, including point mutation, insertion and deletion events in the variable (V), diversity (D) and joining (J) regions of antibody genes in the process of somatic hypermutations caused by activation-induced cytidine deaminase (AID). The above method was used to detect the effects of two DNA polymerase β (Polβ) inhibitors on the mutations in the VDJ regions of antibody genes.

    Methods

    ·CH12F3 cells were treated with lentivirus infection (i.e. treatment group), and the CH12F3 cells before infection were used as control group. Western blotting was used to detect the expression level of AID in the two groups of cells. The high-throughput sequencing libraries were constructed, and the frequencies of point mutation, insertion and deletion in the VDJ regions of antibody genes in the two groups of cells were analyzed by bioinformatics. CH12F3 cells were treated with different concentrations of Polβ inhibitors [2', 3'-dioxycytidine (DDC) and 5- methoxyflavone (5-MF)], and the effects of the two inhibitors on cell proliferation were measured by Trypan blue exclusion method. CH12F3 cells (i.e. experimental group) were treated with the selected DDC concentration or 5-MF concentration, respectively; the cells treated with 0.9% NaCl or DMSO were recorded as the control group of the above experimental group, respectively. The four groups of cells before and after lentivirus infection were detected by the above established methods, and finally high-throughput sequencing was carried out to analyze the effects of the two inhibitors on the frequencies of point mutation, insertion and deletion in the VDJ regions of antibody genes.

    Results

    ·Western blotting results showed that compared with CH12F3 cells in the control group, the expression of AID in CH12F3 cells in the treatment group was higher; and the high-throughput sequencing results showed that there were a large number of point mutations in the VDJ regions of antibody genes of CH12F3 cells in the treatment group, and its frequencies of insertion and deletion were also higher than those of the control group (both P=0.000). Trypan blue exclusion method showed that the optimal concentration of DDC and 5-MF for CH12F3 cells was 100 μmol/L and 25 μmol/L, respectively. The high-throughput sequencing results showed that compared with the 0.9% NaCl control group, the point mutation frequencies in the VDJ regions of antibody genes were decreased after cells were treated by 100 μmol/L DDC (P=0.000), and its 1 bp deletion frequencies decreased slightly (P=0.009); compared with DMSO control group, the frequencies of point mutation (P=0.000), longer than 1 bp insertion and deletion (both P=0.000) in the VDJ regions of antibody genes were decreased after cells were treated by 25 μmol/L 5-MF.

    Conclusion

    ·The in vitro detection method established in this study can be used to analyze the AID-induced mutation events of VDJ regions of antibody genes. The Polβ inhibitors DDC and 5-MF can inhibit the mutations in the VDJ regions of antibody genes induced by AID.

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    Diagnostic value of PSA, TAP and MACC1 expression in blood of patients with prostate cancer
    WANG Hui, ZHAO Ying, WEN Lirong, CAO Jun, YANG Jiping, YUAN Yongming
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (4): 496-501.   DOI: 10.3969/j.issn.1674-8115.2022.04.012
    Abstract546)   HTML12)    PDF(pc) (1080KB)(269)       Save
    Objective

    ·To investigate the expression and diagnostic value of prostate specific antigen (PSA), tumor abnormal protein (TAP) and colon cancer metastasis related gene 1 (MACC1) in the blood of patients with prostate cancer.

    Methods

    ·One hundred and seven patients with prostate cancer (case group) admitted to Dahua Hospital, Xuhui District, Shanghai, from January 2019 to December 2020 were retrospectively analyzed, and 60 healthy people (control group) who underwent physical examination in the hospital in the same period were selected. The levels of blood PSA, TAP and MACC1 in the two groups, as well as their correlation with Gleason score and T stage, were analyzed. Receiver operating characteristic (ROC) curve was used to evaluate the value of various indexes in the diagnosis of prostate cancer.

    Results

    ·The levels of blood PSA, TAP and MACC1 in the case group were significantly higher than those in the control group (P<0.05). With the increase of Gleason grade, the levels of blood PSA, TAP and MACC1 increased gradually. With the progress of T stage, the levels of blood PSA, TAP and MACC1 increased gradually. The levels of PSA and MACC1 in the patients with lymph node metastasis were significantly higher than those without lymph node metastasis, but the levels of TAP in the patients with lymph node metastasis were significantly lower than those without lymph node metastasis (P<0.05). The analysis results of ROC curve showed that the AUC of PSA in the diagnosis of prostate cancer was 0.764, the sensitivity was 86.12%, the specificity was 88.63%, and the cut-off value was 6.01 μg/L. The AUC of TAP in the diagnosis of prostate cancer was 0.796, the sensitivity was 88.18%, the specificity was 89.58%, and the cut-off value was 135.62 μm2. The AUC of MACC1 in the diagnosis of prostate cancer was 0.873, the sensitivity was 78.46%, the specificity was 80.10%, and the cut-off value was 37.80 pg/mL. The AUC (0.941), sensitivity (93.15%) and specificity (94.08%) of combined detection were higher than those of any single detection (P<0.05). Spearman correlation analysis showed that the blood PSA, TAP and MACC1 levels were positively correlated with Gleason score (r=0.648, 0.513, 0.501; P=0.000), and with T stage (r=0.616, 0.537, 0.542; P=0.000).

    Conclusion

    ·Blood PSA, TAP and MACC1 are closely related to Gleason score and T stage of prostate cancer, which has some value in the diagnosis of prostate cancer, and the combined detection of three items has higher diagnostic value.

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    Transcriptomic analysis of metabolic characteristics of the immune cells in systemic lupus erythematosus patients
    HAN Xiaxia, JIANG Yang, GU Shuangshuang, DAI Dai, SHEN Nan
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (9): 1197-1207.   DOI: 10.3969/j.issn.1674-8115.2022.09.006
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    Objective ·To study the metabolic pathway activity level of the immune cell subsets in the patients with systemic lupus erythematosus (SLE) by bioinformatics analysis. Methods ·The matrix expression data of PBMCs collected from SLE patients and healthy controls were downloaded from Gene Expression Omnibus (GEO) Datasets, as well as the transcriptome data of T cell and B cell subsets from SLE patients and healthy controls. The differentially-expressed genes (DEGs) were identified in the standardized sequence data. Pathway enrichment analysis of DEGs was performed by online Enrichr tools, and the common up-regulated pathways were determined by comparative analysis. Gene set enrichment analysis (GSEA) was used to identify pathways that were enriched in the experiment processed with the whole gene expression matrix. RNA-seq data from PBMCs samples of SLE patients and healthy controls were used to characterize the immune cell composition. The targeted pathway was annotated with gene expression. Assay for transposase-accessible chromatin using sequencing (ATAC-seq) technique was performed to detect the chromatin accessibility of glycolysis-related genes in SLE patients and healthy controls. Results ·① Venn diagram depicted 139 common upregulated pathways in GSE169080, GSE144390 and GSE139350 data sets, and GSEA results showed that multiple classical metabolic pathways, including glycolysis, oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO), were up-regulated in SLE patients. ② Immune cell composition analysis of PBMCs showed that the proportions of T cells, B cells and NK cells were higher in SLE patients, and the expression of genes encoding multiple enzymes of metabolic pathway in T cells and B cells were higher than those in healthy controls. ③ Compared to healthy controls, the intensity of ATAC-seq signal was significantly enhanced at transcriptional regulatory sites of SLC2A3, PKM and LDHA in peripheral B cells from SLE patients. ④ GSEA results and visualization analysis of metabolic pathways of SLE B cell subsets showed that the memory B cells and plasmablasts displayed a higher metabolic state than na?ve B cells. Conclusion ·Multiple metabolic pathways are altered in SLE patients and the metabolic level of effector B cells is higher than na?ve B cells in SLE patients.

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    Renewal of esophageal and gastric macrophages by circulating monocytes
    ZHU Yiwen, YU Qing, WU Xinrui, LU Jie, CHEN Zihao, GINHOUX Florent, SU Bing, LIU Zhaoyuan
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (9): 1208-1215.   DOI: 10.3969/j.issn.1674-8115.2022.09.007
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    Objective ·To reveal the renewal kinetics of esophageal and gastric macrophages by circulating monocytes. Methods ·The monocytes of the Ms4a3Cre -RosaTdT fate mapping model mice carry an irreversible tdTomato red fluorescent marker. The macrophages derived from these monocytes will also carry red fluorescence, distinguishing them from the embryonic-derived macrophages. The contribution of monocytes to esophageal and gastric macrophages was determined by detecting the number and the proportion of red fluorescence labeling in the ionized calcium-binding adapter molecule 1 (IBA1) positive macrophages in the esophagus and stomach from Ms4a3Cre -RosaTdT mice of different ages (2 weeks, 8 weeks and 15 months of age) by immunofluorescence imaging. Results ·In the esophagus and stomach of 2-week-old Ms4a3Cre -RosaTdT mice, most macrophages were tdTomato negative, indicating that the esophageal macrophages and gastric macrophages of young mice were mainly embryonic derived. In 8-week-old adult mice, many tdTomato positive monocyte-derived macrophages could be detected in the stomach. In 15-month-old mice, most of the esophageal and gastric macrophages were tdTomato positive, indicating that the esophagus and stomach macrophages of the old mice were mainly produced by monocytes. Conclusion ·In juvenile mice, esophageal and gastric macrophages are mainly embryonic-derived macrophages, while with age, monocyte-derived macrophages gradually replace tissue-resident macrophages in the esophagus and stomach. Esophageal and gastric macrophages in aged mice are mainly derived from circulating monocytes. Thus, the macrophage pool in the esophagus and stomach of mice consists of embryonic- and mononuclear-derived cells with their proportions changing with age.

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    Analysis of genetic and clinical characteristics of PMP22-associated peripheral neuropathy
    ZHU Xiaowei, ZHAN Feixia, ZHANG Chao, LIU Shihua, ZHONG Ping, CAO Li, LUAN Xinghua
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (5): 609-616.   DOI: 10.3969/j.issn.1674-8115.2022.05.008
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    Objective

    ·To investigate the genetic and clinical features of peripheral neuropathy patients with PMP22 gene variations and the association between genotype and clinical phenotype.

    Methods

    ·A total of 162 patients with peripheral neuropathy who were treated in Department of Neurology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine from 2006 to 2022 were collected. Molecular detecting techniques including combining multiplex ligation-dependent probe amplification (MLPA), whole exon sequencing (WES) and Sanger sequencing were used to comprehensively analyze the genetic variation of 162 patients, and 26 probands with PMP22 gene variations and their 33 family members were screened out. The genetic variations included duplication, deletion and point mutations. The clinical and genetic characteristics of 26 patients with PMP22-associated peripheral neuropathy were further analyzed. The clinical characteristics included clinical demographic data, clinical manifestations, electrophysiological and pathological characteristics.

    Results

    ·There were a total of 59 (37 male and 22 female) individuals with PMP22-associated peripheral neuropathy, among whom 46 patients in 13 families had positive family histories and 13 did not. The median age at onset of neuropathy was 34.0 (14.0, 49.5) years old. The initial symptom was limb weakness or limb numbness. There were 51 Charcot-Marie-Tooth type-1A (CMT1A) patients with PMP22 duplication, 6 hereditary neuropathy with liability to pressure palsies (HNPP) patients with PMP22 deletion and 2 Dejerine-Sottas syndrome (DSS) patients with PMP22 point mutations (p.S72L and p.G100V). Sixteen patients underwent electrophysiological detections. Compared with the 4 PMP22 deletion patients, the motor nerve conduction velocity (MCV), compound muscle action potential (CMAP) and sensory nerve conduction velocities (SCV) of 12 PMP22 duplication patients were obviously decreased (all P<0.05). Conduction block was found in both kinds of mutation types. Sural nerve biopsies were performed in 12 patients, including 8 PMP22 duplication, 3 PMP22 deletion and 1 PMP22 point mutation, and pathological changes such as thinning of myelinated nerve fibers, “onion bulbs” and decreased nerve fiber density were observed in varying degrees.

    Conclusion

    ·PMP22 gene-associated neuropathies can be characterized by CMT1A, HNPP and DSS with high clinical heterogeneity. Patients with demyelinating manifestations on electrophysiological detections and sural nerve biopsy need genetic testing for PMP22 gene duplication, deletion and point mutation after ruling out acquired etiology. It is available to help optimize diagnosis and genetic counseling of the disease.

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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
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    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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    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