Table of Content

28 May 2023, Volume 43 Issue 5 Previous Issue   
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Oral surgery
Innovative research team achievement column
Basic research
Clinical research
Review


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Oral surgery

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Clinical analysis and ultrasound study of allergy-related obstructive parotitis LU Yifan, ZHANG Weiqian, YU Chuangqi 2023, 43 (5):  519-523.  doi: 10.3969/j.issn.1674-8115.2023.05.001 Abstract ( 209 )   HTML ( 25 )   PDF (1973KB) ( 156 )   Objective ·To explore the clinical features of allergy-related obstructive parotitis (AROP) and the ultrasonic characteristics of its duct. Methods ·Patients diagnosed with AROP at the Oral Surgery Department of Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine from October 2020 to October 2022 due to recurrent swelling of parotid gland were included. Clinical data of the patients were retrospectively analyzed, including medical history, clinical manifestations, laboratory examinations and imaging examinations. Static ultrasound was used to display the morphological characteristics of the AROP duct, ultrasonic images were used to measure the inner diameter at the widest point of duct dilation, and the degree of duct dilation was graded. Dynamic ultrasound was used to show the morphological changes of the duct at the functional state of AROP patients. The value and ratio of duct widening were calculated, and the symptoms of parotid swelling were recorded. Results ·Thirty-seven patients were diagnosed with AROP and included in the study, including 9 males (24.3%) and 28 females (75.7%). The main clinical symptoms were recurrent swelling of parotid gland, skin itching and duct discharge of mucus plug. Thirty-two patients (86.5%) had a history of systemic allergic disease. The proportion of increased serum IgE concentration and peripheral blood eosinophil (PBE) absolute count was 59.5% and 43.2%, respectively. The static ultrasound results of 37 AROP patients were mainly manifested by duct dilation. The grading results of duct dilation degree were mild in 21 cases (56.8%), moderate in 10 cases (27.0%) and severe in 6 cases (16.2%). Seven patients with AROP underwent dynamic ultrasonography. Results showed that 4 patients were in the asymptomatic period and 3 patients were in the symptomatic period. Conclusion ·AROP is a type of chronic obstructive parotitis closely related to allergic reactions, and its diagnosis should be considered in many aspects. Ultrasound can effectively display the morphological characteristics of parotid duct, and can be used to assess the obstruction status of the duct, which is helpful for the diagnosis and follow-up of AROP. Figures and Tables | References | Related Articles | Metrics

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Development and application of Chinese customized total temporomandibular joint prosthesis CHEN Xuzhuo, MAO Yi, YUAN Dan, ZHANG Shanyong, YANG Chi 2023, 43 (5):  524-531.  doi: 10.3969/j.issn.1674-8115.2023.05.002 Abstract ( 279 )   HTML ( 12 )   PDF (2636KB) ( 203 )   Alloplastic total joint replacement is one of the effective methods for temporomandibular joint (TMJ) reconstruction. As the first choice for TMJ reconstruction, alloplastic total joint replacement has the advantages of no need to open up a second operative area, short operation duration and immediate functional restoration, compared with autogenous bone graft. The customized prosthesis has the edge over the stock prosthesis due to its excellent suitability and less intraoperative bone trimming. However, there are no commercialized counterparts in China yet. Hence, it is urgent to develop a Chinese customized total TMJ prosthesis for Chinese patients. Since 2009, the authors′ team has begun to develop the customized total TMJ prostheses suitable for Chinese anatomical features independently. Through three generations of products, the team gradually realized the stable connection of porous titanium alloys and ultra-high molecular weight polyethylene (UHMWPE), and finally achieved a key technological breakthrough in 2017. The third generation of customized total TMJ prosthesis was successfully developed by friction stir welding technology. The mechanical properties of Chinese customized prostheses have prevailed over its international counterparts, with satisfactory short-term follow-up results based on its preliminary clinical application. Furthermore, in order to ensure high efficiency and accuracy of the procedures from design and manufacture to clinical application, the authors′ team has developed a relatively mature standardized process, and improved the surgical procedures. This review systematically summarizes the research and development of Chinese customized total TMJ prosthesis system in the past decade, and looks forward to the future development of Chinese customized prosthesis system. Figures and Tables | References | Related Articles | Metrics

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Application effect of home-based rehabilitation program led by self-efficacy theory after temporomandibular joint disk repositioning YU Leilei, RUAN Hong, XIA Di, HE Meijuan, SUN Mingyuan, ZHENG Jisi 2023, 43 (5):  532-539.  doi: 10.3969/j.issn.1674-8115.2023.05.003 Abstract ( 143 )   HTML ( 9 )   PDF (1388KB) ( 122 )   Objective ·To explore the effects of home-based rehabilitation program led by self-efficacy theory after temporomandibular joint disk repositioning. Methods ·Convenient sampling method was used. Patients with temporomandibular joint disk displacement who received temporomandibular joint disk repositioning in Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine from August 2020 to January 2021 were selected as the control group, and patients admitted from February 2021 to July 2021 were selected as the intervention group. The control group received the conventional home-based rehabilitation care, while the intervention group were given home-based rehabilitation program led by self-efficacy theory. The general information questionnaire was used to collect the general information about patients. The joint range of motion measuring, rehabilitation exercise compliance questionnaire, General Self-efficacy Scale (GSES), and Mishel's Uncertainty in Illness Scale (MUIS) were used to investigate the joint range of motion, the rehabilitation exercise compliance score, the self-efficacy score and the uncertainty in illness score in the two groups at baseline and at 1, 3 and 6 months after surgery. Results ·A total of 167 patients with temporomandibular joint disk displacement who received temporomandibular joint disk repositioning surgery were enrolled, including 96 cases in the control group and 71 cases in the intervention group. There was no difference in the general information between the two groups (P>0.05). There were no differences in the maximal mouth opening, maximum rightward lateral movement, maximum leftward lateral movement, self-efficacy score and uncertainty in illness score between the two groups at baseline (all P>0.05). The maximal forward extension in the intervention group was significantly less than that in the control group (P=0.008). Repeated measurement variance analysis showed that the self-efficacy scores in the intervention group were higher than those in the control group at 1, 3 and 6 months after surgery, and the differences were statistically significant (P=0.006, P=0.003, P=0.016). At 1 and 3 months after surgery, the scores of complexity dimension of uncertainty in illness in the intervention group were significantly lower than those in the control group (P=0.003, P=0.000). At 1 and 6 months after surgery, the rehabilitation exercise compliance scores in the intervention group were significantly higher than those in the control group (P=0.000, P=0.016). At 6 months after surgery, the maximum forward extension and maximum rightward lateral movement were significantly greater than those in the control group (P=0.024, P=0.008). Conclusion ·The home-based rehabilitation program led by self-efficacy theory has a positive effect on improving the self-efficacy and compliance of rehabilitation exercise, reducing the disease uncertainty, and promoting the joint function recovery in patients receiving temporomandibular joint disk repositioning. Figures and Tables | References | Related Articles | Metrics

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Evaluation of clinical effect of manipulation on masticatory muscle pain guided by MRI YANG Haixia, XU Lili, WANG Bocheng, CHEN Minjie 2023, 43 (5):  540-544.  doi: 10.3969/j.issn.1674-8115.2023.05.004 Abstract ( 152 )   HTML ( 12 )   PDF (1599KB) ( 104 )   Objective ·To assess muscle changes of patients of temporomandibular joint disorder with nonstructural disorder by using the Dixon technique for MRI of masticatory muscle, and evaluate the clinical effect of manipulation on masticatory muscle pain guided by MRI. Methods ·A total of 29 patients with TMD masticatory muscle pain (without disc displacement) who were diagnosed for the first time in the Department of Oral Surgery, Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine from June 2021 to September 2022 were included. Among them, 9 cases who were assessed with Dixon technique for MRI of masticatory muscle were collected and treated by manipulation. Before treatment, the DICOM Viewer workstation was used to compare the value of masticatory muscle pain area (Z1), the value of ipsilateral non-pain area (Z2) and the value of contralateral corresponding masticatory muscle area (Z3) in Dixon image. Manipulation therapy was performed according to the area of abnormal threshold. Follow-up was performed for 1-4 weeks after treatment, the active maximum mouth opening (MMO) and Visual Analogue Scale (VAS) before and after treatment were compared, and the value of masticatory muscle pain area in Dixon image after treatment was obtained again to evaluate the clinical efficacy. Results ·The mean value of Z2 and Z3 in Dixon was (66.23±32.90) and (66.27±33.87), while Z1 in masticatory muscle pain region was (131.94±83.99), which was significantly higher than Z2 and Z3. Manipulation therapy showed significant improvement in MMO and VAS, and the effective rate was 88.89%. Conclusion ·There is a significant correlation between the imaging findings of Dixon technique for MRI and the pain points of the masticatory muscle reported by the clinical complaints. The manipulation therapy guided by Dixon technique for MRI has a significant effect on improving the degree of mouth opening and pain. Figures and Tables | References | Related Articles | Metrics

Innovative research team achievement column

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In vitro therapeutic effects and molecular mechanisms of targeted inhibition of CDK12/13 in high-grade gliomas MEI Yanqing, HAN Yujie, WENG Wenyun, ZHANG Lei, TANG Yujie 2023, 43 (5):  545-559.  doi: 10.3969/j.issn.1674-8115.2023.05.005 Abstract ( 209 )   HTML ( 17 )   PDF (3954KB) ( 323 )   Objective ·To find novel and common targeting strategies for high-grade gliomas (HGGs) from the perspective of epigenetic and transcriptional modulators, test the therapeutic effect in vitro and investigate the related molecular mechanisms. Methods ·Glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG) cell lines with high malignancy and mortality in HGGs were selected for screening of targeted small molecule drug library related to epigenetic transcription and for functional genome screening based on the CRISPR-Cas9 technology. The effect of selected targeted epigenetic transcriptional modulators on growth, proliferation, and apoptosis of GBM and DIPG cell lines were then measured either by CRISPR-Cas9 knockout or treatment with targeted small molecule inhibitors of genes in vitro. Anti-tumor molecular mechanisms of the modulators in corresponding small molecule inhibitors-treated GBM and DIPG cells were explored via RNA-seq transcriptome analysis and further verified by real time quantitative PCR (RT-qPCR), Western blotting and flow cytometry. Results ·Targeted small molecule drug library combined with functional genome screening for epigenetic transcriptional modulators identified CDK12/13 as the novel therapeutic targets for both GBM and DIPG. Knockout out of CDK12 by CRISPR-Cas9 in multiple GBM and DIPG cell lines significantly reduced their in vitro cellular activity. CDK12/13 inhibitors SR-4835 and THZ531 also significantly inhibited the growth of these two types of HGGs cell lines in vitro by antagonizing cell proliferation and promoting cell apoptosis. RNA-seq transcriptome analysis of GBM and DIPG cell lines after SR-4835 treatment showed that genes significantly down-regulated by CDK12/13 inhibitors in HGGs cells were mainly enriched in transcriptional regulation, DNA damage response (DDR) pathway, ubiquitin-proteasome pathway, and cell cycle. Furthermore, a series of experiments demonstrated that targeted inhibition of CDK12/13 significantly down-regulated the transcription of DDR-related genes, resulting in the accumulation of DNA damage, and induced G2-M cell cycle arrest. Conclusion ·CDK12/13 is a common potential therapeutic target of these two types of HGGs, providing theoretical support for the follow-up in vivo verification and combination therapy test. The research also lays the foundation for further clinical application. Figures and Tables | References | Related Articles | Metrics

Basic research

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Bioinformatics analysis of pathological mechanism of degenerated tendon via stress deprivation LI Qinglin, WANG Wenbo, LIU Wei 2023, 43 (5):  560-570.  doi: 10.3969/j.issn.1674-8115.2023.05.006 Abstract ( 163 )   HTML ( 13 )   PDF (5550KB) ( 93 )   Objective ·To explore relevant molecular mechanisms of the stress deprivation model of newborn rats by using bioinformatics analysis. Methods ·A total of 60 SD rats (10 d post-natal) were enrolled in the study. Those the left Achilles tendon of which was severed were chosen as the experimental group (stress deprivation group), and the right Achilles tendon of which was injured by clamping were chosen as the control group (stress group). On the 10th and 20th day after treatment, tissue samples were collected for gross observation of the tendon development, histological staining of the tendon structure, transmission electron microscope observation of the tendon ultrastructure and immunohistochemical analysis of CD31 expression. Differentially expressed proteins between the two groups at two time points were obtained by using protein mass spectrometry, and GO and KEGG enrichment analysis as well as protein-protein interaction (PPI) network anlysis were performed on differential proteins. Results ·The stress-deprived tendon showed tissue enlargement and congestion, disorganized tendon tissue structure and immature collagen fibers. Transmission electron microscopy showed that the development and maturation of collagen fibrils were significantly impaired in the experimental group, and the diameter of collagen fibrils of the severed tendon became thinner on the 20th day after treatment (P=0.001). Immunohistochemistry showed that the severed tendon was relatively vascularized. The results of protein mass spectrometry analysis showed there were 1 865 and 965 differentially expressed proteins on the 10th and 20th day after treatment, including 1 835 and 837 upregulated proteins respectively. GO analysis showed that the upregulated proteins were involved in biological processes such as intracellular protein transport, protein stabilization, mRNA splicing via spliceosome, protein folding and protein import into nucleus. KEGG analysis indentified enhancement of vascular endothelial growth factor (VEGF) signal pathway, mammalian target of rapamycin (mTOR) signal pathway, endocytosis and other signal pathways in the experimental group. PPI network analysis showed various upregulated proteins including Akt1, Hspa4, Hspa5, Eef2, ACTC1 and RhoA. Conclusion ·Stress deprivation can activate multiple signal pathways in tendon cells and lead to tissue vascularization, abnormal collagen development, etc., resulting in degenerative pathological changes of tendons. Figures and Tables | References | Related Articles | Metrics

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Effect of lysine demethylase 5C on renal carcinoma metastasis CHEN Ningdai, ZHOU Bingqian, CHEN Zheyi, CHEN Shiyu, ZHEN Yingxia 2023, 43 (5):  571-579.  doi: 10.3969/j.issn.1674-8115.2023.05.007 Abstract ( 141 )   HTML ( 18 )   PDF (24004KB) ( 327 )   Objective ·To investigate the effects of lysine demethylase 5C (KDM5C) on the migration and invasion of renal clear cell carcinoma, analyze the genes regulated by KDM5C and explore the mechanisms of promoting renal cell carcinoma after its inactivation. Methods ·Lentivirus was used to construct human renal clear cell carcinoma 786-O and Caki-1 cell lines with KDM5C stable knockout. The changes of migration and invasion abilities of renal carcinoma cells were observed by Transwell assay. Epithelial-mesenchymal transition (EMT) protein expression was detected by Western blotting. Differential gene analysis and functional pathway enrichment analysis were performed by using 786-O Control-sg, KDM5C-sg 2 group cell RNA sequencing data and The Cancer Genome Atlas (TCGA) public database to further explore the cancer-promoting mechanisms after KDM5C deletion. The up-regulated EMT-related genes in sequencing data were screened out according to the EMT gene set, and the genes were screened by survival analysis and univariate COX analysis. Finally, LASSO regression analysis and risk forest model were used to further screen genes highly related to the phenotype after KDM5C knockout. Results ·After the deletion of KDM5C, both 786-O and Caki-1 cells showed significant migration and invasion phenotypes compared with control groups. Analysis of TCGA database indicated that mutation of KDM5C in renal cancer patients led to poor prognosis (P=0.042). RNA sequencing analysis showed that KDM5C knockout may affect cell adhesion molecules and upregulate epithelial-mesenchymal transition-related genes. Western blotting detected the increased expression levels of β-catenin, Vimentin and Snail proteins in two kinds of cells after KDM5C knockout. Finally, ten up-regulated EMT genes were obtained by survival analysis and univariate COX analysis for LASSO regression analysis and risk forest model prediction. The results showed that KDM5C may have a regulatory effect on PLAUR gene. Conclusion ·The mutation of KDM5C can promote the development of renal carcinoma by enhancing migration and invasion. Figures and Tables | References | Related Articles | Metrics

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Effect of montelukast on leukotriene B4 metabolism in asthma HU Yu, XIE Liang, ZOU Dan, FU Hongling, LOU Lili, XIE Keqi, LIU Hanmin 2023, 43 (5):  580-591.  doi: 10.3969/j.issn.1674-8115.2023.05.008 Abstract ( 167 )   HTML ( 11 )   PDF (4972KB) ( 138 )   Objective ·To observe the effect of montelukast on the expressions of key genes in LTB4 (leukotriene B4) metabolic pathway in treating asthma and investigate the candidate intervene targets of asthma. Methods ·The acute, subacute, and chronic asthmatic mouse models characterizing by allergic airway disease (AAD) were set up by ovalbumin (OVA) and Al(OH)3 sensitization and challenge and intervened by intragastric administration of montelukast and finally challenged by OVA for chronic asthma model. The pulmonary functions of mice were tested by unconstrained whole body plethysmograph, to quest the change patterns of airway hyperresponsiveness (AHR). The eosinophil (EOS) infiltration and goblet cell (GCL) hyperplasia in mouse lungs were detected by hematoxylin-eosin (HE) staining, to quest the pathologic features of airway allergic inflammation. The levels of immunoglobulin E (IgE), interferon γ (IFN-γ), and interleukin (IL) in bronchoalveolar lavage fluid (BALF) and serum were detected by ELISA and Milliplex kits, to quest the helper T cell type 2 (Th2) inflammation status. The transcription and protein levels of 5-lipoxygenase activating protein (ALOX5AP), leukotriene A4 hydrolase (LTA4H), and leukotriene B4 receptor 1 (BLT1) genes, which encoded the rate-limiting enzymes in LTB4 synthesis pathway, were detected by RT-qPCR, Western blotting and immunohistochemistry (IHC). Results ·The asthmatic mouse model could be set up by OVA and Al (OH)3 and was presented as AHR characterized by increasing enhanced pause (Penh) value, eosinophilic inflammation and high mucous secretion pathologically characterized by airway EOS infiltration and GCL hyperplasia, Th2 inflammation immunologically characterized by the increasing levels of IgE, IL-4, and IL-13 as well as decreasing levels of IFN-γ, IL-2, and IL-12 in BALF and serum. Montelukast could alleviate AAD effectively. The transcription and protein levels of ALOX5AP, LTA4H, and BLT1 genes increased in asthma. Montelukast can inhibit the expression of ALOX5AP gene and promote the expressions of LTB4 and BLT1 genes in asthmatic chronic phase. When challenged by OVA once again, montelukast can induce the significantly high expressions of LTB4 and BLT1 genes. Conclusion ·Montelukast has the effect of relieving allergic inflammation in asthma mice, but it can stimulate the production and accumulation of LTB4 and is significant in chronic phase. When challenged by OVA a second time, LTB4 could be promoted to combine with BLT1 and attend in the pathogenesis of asthma. The results suggested that there was a potential risk of activation of LTB4 by montelukast. The rate-limiting enzyme LTA4H and its receptor BLT1 metabolism may be potential targets for asthma treatment. Figures and Tables | References | Related Articles | Metrics

Clinical research

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Clinical and genetic characteristics of adult cerebral adrenoleukodystrophy LIU Taotao, LIU Xiaoli, WU Jingying, NI Ruilong, ZHANG Mengyuan, JI Duxin, ZHANG Mei, CAO Li 2023, 43 (5):  592-599.  doi: 10.3969/j.issn.1674-8115.2023.05.009 Abstract ( 213 )   HTML ( 12 )   PDF (3732KB) ( 149 )   Objective ·To summarize and analyze the clinical and genetic characteristics of adult cerebral adrenoleukodystrophy(ACALD ). Methods ·The data of eight patients with ACALD who attended the Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University School of Medicine from June 2018 to September 2022 were collected and comprehensively analyzed. Clinical data included age at onset, duration of disease, family history, present history and physical examination. Imaging examinations included magnetic resonance imaging (MRI) of the cranial, cervical spine and thoracic spine. Laboratory tests included serum very-long-chain fatty acids (VLCFA), adrenal cortical function and genetic test. Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (Moca) were used to assess patients′ cognitive function. Results ·A total of 8 male patients with ACALD were included in this study. Ageat onset ranged from 23 to 40 years old with an average age of (32.75±5.80) years, and the disease duration ranged from 4 to 59 months. Patients′ first symptoms were highly variable. Three patients showed memory loss and cognitive dysfunction, two showed irritability and personality change, one showed mental and behavioral abnormalities, one showed dysarthria and ataxia, and one showed persistent dizziness, occipital numbness and insomnia. All the patients had multiple white matter demyelination lesions, and white matter demyelination in parietal occipital lobe and posterior corpus callosum was the most common. Enhancement MRI showed patchy Gd-enhancement of partial lesions in three cases. In two patients, magnetic resonance spectroscopy showed that choline (Cho) peak increased and N-acetyl-aspartate (NAA) peak decreased. Serum VLCFA levels of C26, C24/C22 and C26/C22 were elevated in six patients who underwent serum VLCFA examination. Seven patients underwent adrenal cortical function testing, of which six experienced adrenal cortical dysfunction. Six patients were cognitively impaired, four of whom had decreased MMSE and MoCA scores, and two of whom were unable to cooperate with the assessment due to severe cognitive impairment. Eight different ABCD1 gene mutations were identified, among which c.1750delC (p.H584Tfs*52) and c.160_170delACGCAGGAGGC (p.T54Lfs*137) were novel mutations. Conclusion ·The initial symptoms of ACALD vary, among which memory loss and cognitive dysfunction are the most common. White matter demyelination lesions in the parietal and corpus callosum pressure are the most common, and imaging abnormalities precede neurological symptoms. The clinical features of the disease are hair thinning and skin pigmentation, and the biochemical features are elevated serum VLCFA and adrenal insufficiency. Missense mutations are more common in the ABCD1 gene, and exons 1 and 6 are the hot mutant exons in Chinese. Figures and Tables | References | Related Articles | Metrics

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Changes in serum Th17/Treg-related cytokine levels in periodontitis patients with Alzheimer′s disease XIE Xinyi, ZHOU Wei, QIU Che, SHEN Hui, SONG Zhongchen 2023, 43 (5):  600-605.  doi: 10.3969/j.issn.1674-8115.2023.05.010 Abstract ( 154 )   HTML ( 14 )   PDF (1859KB) ( 150 )   Objective ·To observe the role of serum Th17/Treg levels in the correlation between Alzheimer′s disease and periodontitis. Methods ·Eighteen periodontitis patients with Alzheimer′s disease who visited the Department of Geriatric, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, and 15 periodontitis patients with normal cognitive function who visited the Department of Periodontology, Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine from June 2020 to December 2021, were enrolled in this study. Probing depth (PD), clinical attachment loss (CAL) and percentage of bleeding on probing (BOP%) were examined and recorded. Serum levels of Th17-related cytokines interleukin-6 (IL-6), IL-17, and IL-22, Treg-related cytokines IL-4 and IL-10, and transforming growth factor-β (TGF-β) were measured by ELISA. The differences of periodontal status and cytokine levels were compared by using t-test. The difference was statistically significant when P<0.05. Results ·The PD (P=0.021), CAL (P=0.018) and BOP% (P=0.018) were significantly higher in the periodontitis patients with Alzheimer′s disease than those in periodontitis patients with normal cognitive function. The serum IL-6 (P=0.010), IL-17 (P=0.022) and IL-22 (P=0.031) levels were significantly higher in the periodontitis patients with Alzheimer′s disease than those in periodontitis patients with normal cognitive function, while the levels of IL-10 (P=0.049), IL-4 (P=0.002) and TGF-β (P=0.006) in the periodontitis patients with Alzheimer′s disease were significantly lower compared with those in periodontitis patients with normal cognitive function. Conclusion ·The periodontal condition of periodontitis patients with Alzheimer′s disease is worse compared to that of periodontitis patients with normal cognitive function. The expression of Th17-related pro-inflammatory cytokines is elevated, while the expression of Treg-related anti-inflammatory factors is decreased. Thus, periodontitis may affect the development of Alzheimer′s disease by mediating Th17/Treg-related chronic inflammatory responses. Figures and Tables | References | Related Articles | Metrics

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A comparative study of prepulse inhibition in children with first episode schizophrenia and normal children XU Xiaojun, YE Minjie, WANG Yuchen, WANG Wenxia, QIAN Sheng, YE Dandi, PAN Lele, HU Xin, YIN Xiaoli, LI Meihua, LING Guangyao 2023, 43 (5):  606-610.  doi: 10.3969/j.issn.1674-8115.2023.05.011 Abstract ( 155 )   HTML ( 17 )   PDF (1316KB) ( 121 )   Objective ·To explore the characteristics of sensory gating and its variation in children with first episode schizophrenia (COS) by using a new technique of prepulse suppression (PI). Methods ·By using the ERP recording and analysis system of brain products, PI was detected in 56 patients with COS and 38 healthy children (NC) using the paradigm of single strong stimulus and weak stimulus+strong stimulus. The patients′ performance was comprehensively evaluated with Positive and Negative Syndrome Scale (PANSS), Social Disability Screening Schedule (SDSS), Social Adjustment Rating Scale (SSRS), and Family Interview Schedule (FIS). Results ·The social objective support formed by summing up the above scales was compared with the quantitative stanard of social support [the standard of social support scale was (8±2) points, and the value of COS group was (10±3) points], and the difference was statistically significant (P=0.007). No correlation was found between PI and PANSS total score and each factor score (all P>0.05). The latency of startle reflex in the COS group was longer than that in the NC group [the NC group was (86±11) ms, the COS group was (97±13) ms, P=0.001]. In the COS group, the amplitude of startle reflex of weak stimulus+strong stimulus was higher, and the latency was longer than that of the NC group [NC group: (39±12) μV, COS group (47±21) μV, P=0.007; the latency of the normal group was (84±17) ms, and that of the COS group was (97±20) ms, P=0.003]. PI inhibition rate in the COS group was lower than that in the NC group [(66±32) % in the NC group, (43±37) % in the COS group, P=0.000]. Conclusion ·COS patients have the same PI abnormality as adult schizophrenia. The change of PI inhibition may be the result of biological markers reflecting the change of agitated emotion in COS patients. Figures and Tables | References | Related Articles | Metrics

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Advances in immunotherapy of advanced non-small cell lung cancer with EGFR mutation HUANG Huayan, XU-ZHANG Wendi, XIA Liliang, YU Yongfeng, LU Shun 2023, 43 (5):  611-618.  doi: 10.3969/j.issn.1674-8115.2023.05.012 Abstract ( 197 )   HTML ( 21 )   PDF (1263KB) ( 140 )   The incidence of epidermal growth factor receptor (EGFR) mutation in non-small cell lung cancer (NSCLC) in Asians is significantly higher than that in Westerners. For the past few years, immune checkpoint inhibitors (ICIs) that target the programmed cell death 1 (PD-1) /programmed cell death ligand 1 (PD-L1) axis have become a part of the treatment paradigm for advanced NSCLC, opening a new era of immunotherapy for lung cancer. However, previous clinical trials reported that advanced NSCLC patients with EGFR mutation could not benefit from ICIs monotherapy. The immunotherapy outcomes of different EGFR mutant subtypes showed diverse. The interim results of the latest clinical trial ORIENT-31 showed that immunotherapy combined with chemotherapy and anti-angiogenesis significantly improved the progression-free survival of EGFR tyrosine kinase inhibitors (TKIs) resistant advanced NSCLC patients, providing a new therapeutic strategy for those EGFR mutant patients. The tumor microenvironment of EGFR-mutated NSCLC is immunosuppressed. Targeting the key immunomodulatory factors that play important roles in the immunosuppression may promote the response of EGFR-mutated tumors to immunotherapy and provide a new synergistic immune combination therapy strategy, which will enrich the clinical treatment options and improve the survival prognosis of EGFR-TKIs-resistant NSCLC patients. This article summarizes the latest clinical progression of immunotherapy in advanced NSCLC with EGFR mutation, the differences of immunotherapy efficacy among different EGFR mutation subtypes, the synergistic mechanism of combined immunotherapy and the potential molecular target combining with immunotherapy in EGFR-mutated NSCLC. References | Related Articles | Metrics

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Research progress in the roles of airway epithelial cells in the pathogenesis of asthma XU Yinglian, TIAN Jing, ZHANG Xiang, ZHAO Shunying 2023, 43 (5):  619-623.  doi: 10.3969/j.issn.1674-8115.2023.05.013 Abstract ( 279 )   HTML ( 16 )   PDF (1246KB) ( 276 )   Asthma is a common chronic respiratory disease, and as a heterogeneous disease, it is driven by a combination of immune, genetic, and environmental factors and involves multiple cells. In recent years, there has been increasing evidence that airway epithelial cells play a core role in the pathogenesis of asthma. As the first line of defense of the respiratory system against the external environment, airway epithelial cells mainly prevent harmful stimuli from entering through various intercellular connections and remove harmful foreign factors such as allergens and viruses through the mucus and cilia system and the antimicrobial peptides. The airway epithelial barrier can be disrupted when the airway mucosa is exposed to foreign harmful stimuli, and epithelial cells can release various epithelial-derived cytokines that effectively activate dendritic cells and type Ⅱ innate lymphoid cells, thereby triggering a subsequent helper T cell 2 immune cascade response that leads to the development of asthma. In view of these roles of airway epithelial cells in asthma, targeted therapeutic agents targeting the cytokines from airway epithelial cells such as thymic stromal lymphopoietin, are gradually coming into clinical use. This article reviews the role of airway epithelial cells in the pathogenesis of asthma and the future clinical applications of therapies targeting airway epithelial cells as potential targets. References | Related Articles | Metrics

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Research progress of tumor-associated macrophages in immune microenvironment and targeted therapy of osteosarcoma WEI Lanyi, XUE Xiaochuan, CHEN Junjun, YANG Quanjun, WANG Mengyue, HAN Yonglong 2023, 43 (5):  624-630.  doi: 10.3969/j.issn.1674-8115.2023.05.014 Abstract ( 231 )   HTML ( 18 )   PDF (1285KB) ( 230 )   Osteosarcoma (OS) is a common primary malignant bone tumor in children and adolescents. The high recurrence and metastasis rate have become a common clinical problem to be solved, but there is no effective treatment. In recent years, studies have suggested that targeting the tumor microenvironment will likely become a new treatment direction for OS. Immune cell infiltration in the tumor microenvironment can promote tumor inflammation and angiogenesis. Tumor-associated macrophages (TAMs) are the most important immune cells in the tumor microenvironment, which play important roles in the development and metastasis of OS. The article reviews the effect of TAMs polarization on tumor cells and describes the effect of TAMs on the occurrence and development of OS from five aspects, including TAMs affecting the growth, invasion and metastasis, mediating chemotherapy resistance, stem cell-like phenotype, and immunosuppression of OS. The review summarizes the research progress of targeting TAMs in the treatment of OS in the past years, including influencing the recruitment of TAMs, promoting the polarization of M2 type to M1 type, targeting CD47 to promote the phagocytosis of TAMs, and targeting the immune checkpoint of TAMs, aiming to provide new directions and ideas for targeted therapy of OS. References | Related Articles | Metrics

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Research progress in the pathogenesis and prognosis of ZNF384 fusion subtype acute leukemia LI Ying, TAN Yangxia, YIN Hongxin, JIANG Yanling, CHEN Li, MENG Guoyu 2023, 43 (5):  631-640.  doi: 10.3969/j.issn.1674-8115.2023.05.015 Abstract ( 423 )   HTML ( 13 )   PDF (2268KB) ( 217 )   Gene fusions caused by chromosomal translocations have become the main pathogenic factors that initiate leukemogenesis. Zinc finger protein 384 (ZNF384) fusion, as an atypical fusion gene in acute leukemia (AL), has widely been identified in different age groups. ZNF384 rearranged 18 genes, with E1A binding protein p300 (EP300), transcription factor 3, (TCF3), and TATA-box binding protein-associated factor 15 (TAF15) being the most common fusion partners. These fusion proteins maintain the complete structure of ZNF384, but the fusion partners are missing in varying degrees, indicating that the mechanisms behind different subtypes of carcinogenesis have similarities. The mechanism of ZNF384-rearranged AL is also being actively investigated. It is mainly believed that the fusion protein regulates the transcription and expression of downstream proteins through chromatin remodeling, and plays a potential role in the differentiation of hematopoietic stem cells, the proliferation and apoptosis of cancer cells and genome repair. Patients with ZNF384 fusions express both lymphoid and myeloid-specific antigens, which have lineage-transforming properties during disease progression. The diversity of immunophenotypes leads to ambiguity in treatment options and diverse outcomes in prognosis studies, and affects the clinical outcome of patients together with fusion subtype and age of onset. Through the statistical analysis of published cases and large-scale cohort studies in the past 10 years, the incidence of ZNF384 fusion in AL and the frequency of each fusion subtype in the context of existing research were further confirmed. The impact of different treatment methods on the prognosis of patients was analyzed, and the identified mechanisms were summarized in order to provide reference for subsequent diagnosis, treatment and research of this unique AL subtype. Figures and Tables | References | Related Articles | Metrics

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Research progress in the relationship between gut microbia and its metabolites and gestational diabetes mellitus LIU Qianruo, FANG Zichen, WU Yuhan, ZHONG Xianxin, GUO Muhe, JIA Jie 2023, 43 (5):  641-647.  doi: 10.3969/j.issn.1674-8115.2023.05.016 Abstract ( 209 )   HTML ( 16 )   PDF (1350KB) ( 162 )   The global incidence of gestational diabetes mellitus (GDM) continues to rise in recent years. Research has shown that GDM can increase the risk of adverse pregnancy outcomes in pregnant women and lead to malignant intergenerational circulation. The etiology of GDM is complex and the pathogenesis has not been fully elucidated. Maternal dietary assessment and guidance is the first-line method for managing GDM in clinical practice. Reasonable diet plays an important role in gut microbia and its metabolites during pregnancy, and the dysfunction of gut microbia is closely related to the occurrence of metabolic diseases. It has been shown that gut microbial metabolites such as short-chain fatty acids (SCFAs), trimethylamine oxide (TMAO) and bile acids are strongly influenced by diet and play an important role in metabolic disorders related to insulin resistance (such as GDM). Progress has been made in the prevention and treatment of metabolic diseases by improving gut microbia through medical nutrition therapy, which provides a new direction for the control of GDM. The status quo of GDM, the characteristics and alteration of gut microbia in pregnant women with GDM, the GDM-related gut microbial metabolites, and the feasible prevention and treatment of GDM by targeting gut microbia and its metabolites are reviewed. References | Related Articles | Metrics

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Progress in morphology of temporomandibular joints in different sagittal skeletal patterns WANG Sijie, SI Jiaping, ZHOU Yu, LUO Dingwen, GAO Lu, CHEN Xiaoyan 2023, 43 (5):  648-654.  doi: 10.3969/j.issn.1674-8115.2023.05.017 Abstract ( 164 )   HTML ( 12 )   PDF (1319KB) ( 212 )   The temporomandibular joint (TMJ) is the most important oral-maxillo-facial joint. Its morphological structure and physiological function are of great significance on long-term stability of treatment results for orthodontics, prosthodontics, occlusal reconstruction, and orthognathic patients. The morphological characteristics of TMJ are affected by many factors, including the cranio-maxillo-facial anatomy, sagittal and vertical skeletal patterns, occlusion of dentition, and function of masticatory muscle. In recent years, due to the improvement of prosthodontic and orthodontic treatment concepts and imaging technology, studies on the distinction of TMJ morphology among different sagittal skeletal patterns have increased. However, there are some differences in the results, and there is a lack of review and summary, leading to no definite conclusions at present. This article aims to summarize the relationship between TMJ morphology and sagittal skeletal patterns from the view of position and morphology of the glenoid fossa and condyle, and analyze the differences among various studies, hoping to further clarify the relationship between different sagittal skeletal patterns and the TMJ morphological characteristics. References | Related Articles | Metrics