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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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    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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    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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    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

    Research progress in clinical characteristics, diagnosis and prognosis of TdT-negative lymphoblastic lymphoma/acute lymphoblastic leukemia
    HOU Shumin, SHAO Jingbo
    Journal of Shanghai Jiao Tong University (Medical Science)   
    Online available: 18 January 2023

    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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    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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    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
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    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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    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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    Anatomical structure of laminar specific subtypes of medial prefrontal cortex-basolateral amygdala projection neurons
    HE Luyao, HUANG Dongping, SHAO Mengmeng, ZHANG Kai, REN Baihui, KONG Qingdan, XU Tianle, LÜ Jiangteng
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (9): 1216-1224.   DOI: 10.3969/j.issn.1674-8115.2022.09.008
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    Objective ·To dissect the fine anatomical structure of medial prefrontal cortex (mPFC)-basolateral amygdala (BLA) projection neurons based on regional and laminar specificity in the cortex in mice. Methods ·The retrograde tracer of adeno-associated viral (AAV) vectors were injected into BLA of C57BL/6 mice. Twenty-one days after the injection, the mice were sacrificed and the brains were harvested. The coronal sections containing mPFC were prepared by using a cryostat microtome. The images were taken by fluorescence microscopy. Then the representative brain slices containing mPFC were selected and the distribution of virus-labeled cell bodies in different subregions of mPFC was analyzed. By using transgenic mouse lines (Tbr2-CreER::LSL-Flp mice and Rbp4-Cre mice) with Flp- or Cre-dependent AAV, layer 2 (L2) and layer 5 (L5) projection neurons in mPFC and their axons in BLA were marked, respectively. Twenty-eight days after the injection, the mice were sacrificed and the brains were also harvested. Coronal sections of the BLA were collected. The brain slices were imaged by fluorescence microscopy after immunofluorescence staining. By measuring the fluorescence intensity of projecting axons in different regions within BLA, the spatial distributions of the axons in BLA of mPFC L2 and L5 projection neurons were compared. Results ·Through fluorescence microscopy and quantitative analysis, it was found that the cell bodies of BLA projection neurons were mainly located at L2 and L5 in the dorsal mPFC (dmPFC) which contains anterior cingulate cortex and prelimbic cortex. However, the distribution of BLA projection neurons in the ventral mPFC (vmPFC) including medial orbital cortex and infralimbic cortex did not exhibit the similar distribution. When studying the axonal distribution of dmPFC projection neurons in two layers, it was found that the axons of L2 projection neurons dispersed in the BLA, while the axons of L5 projection neurons were mainly located in the dorsal region of BLA. Conclusion ·The cell body distribution of mPFC-BLA projection neurons shows regional specificity and laminar specificity. The axon projections initiated from different layers of dmPFC also exhibit regional specificity in BLA.

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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
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    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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    Treatment-free remission after imatinib discontinuation in patients with chronic myeloid leukemia
    XU Tianxue, QIAN Ying, LIU Zhanyun, CAI Gang, WU Yingli, LI Junmin, SHEN Zhixiang, ZHOU Li
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (10): 1413-1419.   DOI: 10.3969/j.issn.1674-8115.2022.10.006
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    Objective ·To analyze the outcomes of treatment-free remission (TFR) after imatinib discontinuation in patients with chronic myeloid leukemia in chronic phase (CML-CP) who meet the criteria for TFR and are willing to monitor the disease regularly, the prognostic factors and the application of droplet digital polymerase chain reaction (ddPCR) technique in monitoring TFR. Methods ·The patients with CML-CP enrolled in this study were monitored regularly after imatinib discontinuation. Molecular response and relapse were analyzed by quantitative polymerase chain reaction (QPCR) for detection of BCR-ABL transcripts. The lymphocytes subsets pre- and post-imatinib discontinuation were evaluated by flow cytometry. ddPCR was used to detect BCR-ABL and the predictive role in TFR was analyzed. Results ·① Forty-two CML-CP patients who met the criteria for TFR were assessed. With median follow-up time 41(5?93) months, 32 (76.2%) patients maintained TFR.The estimated TFR rate by 12, 24 and 48 months were 85.1%, 75.1% and 70.1%, respectively. Median TFR duration was 41 (2?93) months. The most common adverse event post-discontinuation was musculoskeletal pain of grade Ⅰ?Ⅱ (31.0%). Eight patients achieved deep molecular response (DMR) after restart of imatinib. ②58.3% of patients with continuous positive ddPCR developed molecular relapse after imatinib discontinuation, while none relapsed in those with negative detection (P<0.01). ③ The percentage of CD8+CD28- cells pre-discontinuation was lower, while the percentage of CD4+CD25+ cells post-discontinuation was higher in relapsed patients than that in TFR patients (6.2% vs 12.6%, P=0.026; 3.2% vs 2.1%, P=0.021). Conclusion ·CML-CP patients who meet the criteria of TFR may successfully maintain TFR after TKI discontinuation. ddPCR may help to predict the outcome of TFR and detect the molecular relapse earlier. Immune regulation by different T cell subsets may play a role in TFR duration to prevent relapse of disease.

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    Comparison of the root coverage and esthetic outcomes of 3 different techniques for gingival recession
    SUN Wentao, SUN Mengjun, XIE Yufeng, SHU Rong
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (11): 1550-1556.   DOI: 10.3969/j.issn.1674-8115.2022.11.005
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    Objective ·To evaluate the outcomes of connective tissue graft (CTG) combined with 3 different techniques for gingiva recession (GR) including envelope technique, tunnel technique (TUN) and vestibular incision subperiosteal tunnel access (VISTA), and analyze the differences of root coverage and esthetic outcomes of the 3 techniques. Methods ·A total of 87 patients who visited the Department of Periodontology, Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine from January 2020 to December 2021 with a total of 324 GRs were enrolled in this study. All GRs were treated with one of the 3 techniques. The patients′ periodontal conditions were examined at baseline and 6 months after surgery. The root coverage esthetic score (RES) and mucosal scarring index (MSI) were evaluated by 2 periodontists 6 months after surgery. The differences of keratinized gingiva (KG) and GR at baseline and 6 months after surgery were compared by using t-test. Analysis of variance was used to compare the differences of percentage of root coverage (PRC), RES and MSI of different techniques, the same technique in different regions, and different techniques in each region. Results ·In this study, KG increased by (1.49±1.36) mm, and there was a significant difference between each technique (P=0.002). GR decreased by (2.37±1.37) mm, and there was a significant difference between each technique (P=0.000). The mean PRC was (87.7±27.1)%, which was significantly different between each technique (P=0.003). The percentage of complete root coverage (PCRC) was 74.0%, and there was significant difference among the 3 techniques (P=0.000). There were significant differences in RES in different regions between envelope+CTG and VISTA+CTG (Penvelope=0.003, PVISTA=0.000). There was a significant difference in MSI of different regions in VISTA+CTG (P=0.000). Among the 3 techniques, only PRC had differences in the lower anterior teeth (P=0.011); there was a significant difference in RES between lower anterior teeth and lower posterior teeth (PLA=0.001,PLP=0.034), the RES of lower anterior teeth treated with TUN+CTG was higher, and the RES of lower posterior teeth treated with TUN+CTG and VISTA+CTG was higher; there were significant differences in MSI in each region (PUA=0.011, PUP=0.000, PLA=0.003, PLA=0.001). Conclusion ·All the 3 techniques are capable of reducing GR and widening KG. The root coverage and esthetic outcomes of TUN+CTG are superior to the other 2 techniques if the operator′s experience is not considered.

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    Mediating effects of neuroticism and immature defense on relationship between childhood trauma and obsessive-compulsive symptoms in patients with obsessive-compulsive disorder
    ZHAO Qing, GU Wenjie, WANG Zhen
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (9): 1315-1322.   DOI: 10.3969/j.issn.1674-8115.2022.09.019
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    Objective ·To explore the characteristics of childhood trauma, personality traits and defense mechanism in the patients with obsessive-compulsive disorder (OCD), and investigate the mediating effects of personality traits and defense style on the relationship between childhood trauma and obsessive-compulsive symptoms in the OCD patients. Methods ·Totally 113 patients with OCD who met the criteria of Diagnostic and Statistical Manual of Mental Disorders-5 (DMS-5), and 66 age- and gender-matched health controls with similar education level distribution were selected. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used to evaluate the severity of obsessive-compulsive symptoms. Childhood Trauma Questionnaire (CTQ) was used to evaluate the childhood trauma experience. NEO Five-Factor Inventory (NEO-FFI) was used to measure the personality traits. Defense Style Questionnaire (DSQ) was used to evaluate the defense style. The correlations among childhood experience, obsessive-compulsive symptoms, personality traits and defense style as well as mediating role of personality traits and defense style between childhood trauma and obsessive-compulsive symptoms were analyzed. Results ·Compared with the health controls, the OCD patients showed higher scores of emotional abuse [8 (5, 25) points vs 6 (5, 22) points, P<0.05] and immature defense [(4.65±1.01) points vs (3.60±0.99) points, P<0.05]. In the OCD patients, the scores of emotional abuse (r=0.211, P<0.05) and immature defense (r=0.274, P<0.05) were positively correlated with the total scores of Y-BOCS, and the neuroticism scores of NEO-FFI were positively correlated with the total scores of Y-BOCS (r=0.468, P<0.05). The pathway analysis showed the indirect effect from emotional abuse to Y-BOCS via immature defense was 0.088 (95%CI 0.003?0.173, P<0.05). The immature defense played a completely mediated role, and indirect effect from emotional abuse to immature defense via neuroticism was 0.117 (95%CI 0.014?0.219, P<0.05). Conclusion ·Compared with healthy people, OCD patients have experienced more emotional and physical childhood trauma, and have abnormal personality traits of neuroticism, extraversion and conscientiousness. They tend to use immature defense mechanisms. The emotional abuse has an impact on immature defense via neuroticism, and finally affect the obsessive-compulsive symptoms.

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    Accuracy of dental implant placement in fully edentulous patients using a dynamic navigation system
    TAO Baoxin, LAN Kengliang, HUANG Wei, WANG Feng, SHEN Yihan, WU Yiqun
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (9): 1353-1360.   DOI: 10.3969/j.issn.1674-8115.2022.09.024
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    Objective ·To study the accuracy of dental implant placement in fully edentulous patients using a dynamic navigation system. Methods ·Nine fully edentulous patients [8 males and 1 female with the mean age of (48.78±15.25) years old], including 5 maxillae and 4 mandibles, from December 2020 to January 2022, in the Department of Second Dental Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine were included, where 56 implants were placed by a dynamic navigation system and 1 was by freehand. The preoperative plans and the postoperative cone-beam CT were fused, and the entry deviation, exit deviation and angle deviation between the planned and placed dental implants were measured and recorded. According to different jaws, the implants were divided into maxilla and mandible group, and the implants were split into left and right group according to their locations to the midline. The dental implants were classified into anterior and posterior group based on the placed location. The differences of the three deviations between different groups were analyzed by using approximate t test and Mann-Whitney U test. Results ·The median (lower quartile, upper quartile) of entry deviation, exit deviation and angle deviation of dental implants were 1.06 (0.54, 1.54) mm, 1.11 (0.51, 1.56) mm and 3.33° (1.77°, 4.52°), respectively. No significant difference was found in the three deviations, irrespective of the different jaws (maxilla and mandible) (P>0.05) and implant locations (left and right side) (P>0.05). The angle deviation of the anterior implants was significantly higher than that of the posterior implants (P=0.029), but the entry deviation and exit deviation showed no significant difference between the anterior and posterior group (P>0.05). Conclusion ·The dynamic navigation system can achieve acceptable accuracy of dental implant placement in the fully edentulous patients.

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    Exploratory study on detection of cervical lymph node metastasis and extra-nodal extension of oral squamous cell carcinoma using fluorescent probe cMBP-ICG
    YANG lin, WANG Jingbo, HUANG Xiaojuan, REN Jiliang, YUAN ying, TAO Xiaofeng
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (9): 1296-1302.   DOI: 10.3969/j.issn.1674-8115.2022.09.016
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    Objective ·To explore the feasibility of intraoperative real-time fluorescence imaging in the diagnosis of oral cancer cervical lymph node metastasis and extra-nodal extension (ENE) in the patients with oral squamous cell carcinoma (OSCC) by using the surface-smeared fluorescent probe cellular-mesenchymal epithelial transition factor (c-Met)?binding peptide (cMBP)? indocyanine green (ICG). Methods ·The five patients with primary OSCC in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine were selected as the research subjects. The fluorescent probe cMBP-ICG was prepared, and real-time fluorescence imaging was performed by surface smear method on the suspicious lymph nodes of the enrolled patients who underwent neck lymph node dissection. The clinical information, the pathological results and the fluorescence intensity (FI) values of lymph node real-time fluorescence imaging were collected and sorted, and lymph node metastasis and ENE were predicted according to the FIs of cMBP-ICG real-time fluorescence imaging. Results ·Intraoperative cMBP-ICG real-time fluorescence imaging of suspicious lymph nodes were performed, and imaging results of different FIs were obtained in real time. The results of 49 suspicious lymph nodes in the 5 patients showed that the sensitivity of cMBP-ICG in predicting lymph node metastasis was 100%, the specificity was 84%, the positive predictive value was 67%, and the negative predictive value was 100%. The sensitivity of cMBP-ICG in predicting lymph node ENE was 100%, the specificity was 93%, the positive predictive value was 63%, and the negative predictive value was 100%. Conclusion ·Intraoperative cMBP-ICG real-time fluorescence imaging can effectively identify lymph node metastatic and ENE in OSCC, which can provide an auxiliary method for intraoperative diagnosis of lymph node metastasis and ENE.

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    Advances in postoperative adjuvant targeted therapy for patients with stage ⅠB-ⅢA non-small cell lung cancer
    LI Ruonan, CHEN Xiaoke, XU Yuanyuan, TAN Qiang
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (11): 1612-1619.   DOI: 10.3969/j.issn.1674-8115.2022.11.014
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    As the cancer with the highest mortality rate in the world, the treatment of lung cancer has always been a difficult problem for a wide range of patients and physicians alike. Based on the degree of differentiation, morphological features and biological characteristics, lung cancer can be divided into small cell lung cancer and non-small cell lung cancer (NSCLC). The incidence of NSCLC accounts for 80%?85%. Clinically, the treatment options of NSCLC include surgery, chemotherapy, radiotherapy, targeted drug therapy, immunotherapy, etc. For the patients with stage ⅠB?ⅢA NSCLC, in addition to the first choice of surgical treatment, postoperative adjuvant therapy is applied to reduce tumor recurrence and metastasis. Studies have shown that targeted drugs are efficient and safe in the adjuvant therapy for NSCLC patients, and the most attention has been given to agents that target mutations in the epidermal growth factor receptor (EGFR) gene, such as epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). At present, three generations of EGFR TKIs have been approved for clinical use. Among them, the first generation EGFR-TKIs are dominant in the research and application of adjuvant therapy. For example, erlotinib and gefitinib can prolong the disease-free survival (DFS) and overall survival (OS) of patients after surgery, and icotinib has been approved for postoperative adjuvant therapy in China because of its obvious improvement of patients' DFS. Compared with the placebo, the third generation EGFR-TKIs drug osimertinib demonstrated a more significant DFS advantage in the ADAURA trial, decreased tumor recurrence in central nervous system and brought greater benefits in DFS to patients previously treated with standard chemotherapy regime. Osimertinib or chemotherapy combined with osimertinib has therefore become the standard of care for the patients with postoperative adjuvant therapy of stage ⅠB?ⅢA NSCLC. As the third generation EGFR-TKIs new drugs, the clinical trials of almonertinib and furmonertinib for postoperative adjuvant therapy are also underway. This article systematically summarizes the structure of EGFR, the types and detection methods of EGFR gene mutations, introduces the treatment strategies of clinical use of EGFR-TKIs, and discusses the problems that may be encountered in the clinical use of EGFR-TKIs.

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    Weekly paclitaxel in combination with cisplatin in the first-line treatment of metastatic breast cancer: a retrospective study
    WANG Yuzheng, SU Juncheng, TANG Lei, XU Yingchun, ZHANG Fengchun
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (10): 1420-1427.   DOI: 10.3969/j.issn.1674-8115.2022.10.007
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    Objective ·To investigate the efficacy and safety of weekly paclitaxel in combination with cisplatin (DP) as first-line regimen compared with other treatment of physician's choices (TPC) for metastatic breast cancer (MBC). Methods ·The clinical data of 117 MBC patients who were hospitalized in the Department of Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine from July 2008 to June 2021 were retrospectively analyzed. Fifty-five patients were divided into DP group and 62 patients were divided into TPC group, according to whether the DP regimen was used as first-line chemotherapy. The DP group received paclitaxel 80 mg/m2 combined with cisplatin 25 mg/m2, administered on the 1st, 8th and 15th day, respectively, every 28 d as a cycle, a total of 6 cycles of treatment. TPC group received other first-linechemotherapy regimens, including single or combined regimens of capecitabine, gemcitabine, docetaxel and other regimens.Clinicopathologic characteristics including age, menopausal status, pathological results and molecular subtypes were collected and analyzed. Objective response rate (ORR) and clinical benefit rate (CBR) were used to evaluate the efficacy of different regimens based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The adverse effects (AEs) were assessed in accordance with National Cancer Institute's criteria for common adverse effect 5.0 (NCI CTC 5.0), and NCI Ⅲ/Ⅳ AEs were analyzed as severe AEs. The numbers and sites of MBC relapses were analyzed as progression pattern. The differences of clinicopathologic characteristics, efficacy and severe AEs between the two groups were compared by χ2 test. Kaplan-Meier survival analysis was used to compare the difference of first-line progression free survival (PFS1) between the two groups, and the factors with probable influence on PFS1, including clinicopathologic characteristics, treatments and other factors were analyzed. The univariate Cox regression analysis was further applied to analysis of the possible influencing factors screened above. Results ·Except the progesterone receptor (PR) expression (P=0.048), there was no significant difference in clinicopathologic characteristics between the two groups (P>0.05). The ORR (47.3% vs 22.6%, P=0.009) and CBR (78.2% vs 41.9%, P=0.002) in the DP group were significantly higher than those in the TPC group. The median PFS1 was 12.0 months (95%CI 10.0?15.0 months) in the DP group, while the median PFS1 was 6.0 months (95%CI 5.0?9.0 month) in the TPC group, demonstrating significant difference (Log-rank P=0.000). Only the factor "receiving DP regimen as first-line chemotherapy" was recognized as a protective factor for MBC progression by univariate Cox analysis (P=0.000, HR=0.419, 95%CI 0.271?0.649). There was no significant difference (P>0.05) in the progression pattern between the two groups except for fewer bone metastasis (P=0.006). The AEs of the two groups were tolerable, and there was no significant difference in the proportion of severe AEs between the two groups (P>0.05). Conclusion ·The first-line DP regimen demonstrates better efficacy and prolonged PFS1 than TPC regimens. It could be an effective selection and should be considered for MBC according to the clinical situations.

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    A case of neonatal MIRAGE syndrome caused by novel mutation of SAMD9 gene
    LI Yahui, WANG Yiwen, XIE Lijuan
    Journal of Shanghai Jiao Tong University (Medical Science)    2022, 42 (11): 1644-1648.   DOI: 10.3969/j.issn.1674-8115.2022.11.019
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    A female newborn, delivered by cesarean section for oligohydramnios and severe intrauterine growth retardation at gestational age of 30 weeks. She presented progressive severe respiratory distress and symptoms of adrenal insufficiency, such as hyperpigmentation, hypotension, disorder of electrolyte and glucose metabolism soon after birth. The newborn died at the fifth day because of multiple organ failure. Gene analysis showed that there was heterozygous variant in the SAMD9 gene of the newborn (c.4598G>A, p.Arg1533Gln) and she was diagnosed with MIRAGE syndrome (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy). MIRAGE syndrome is usually complex and critical with multisystem disorder. Early identification with genetic testing can help diagnosis and guide treatment, which can improve the prognosis.

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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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