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Diagnostic strategies for oral manifestations of infectious diseases
CHEN Qianming,LI Zaiye,ZENG Xin
J Zhejiang Univ (Med Sci), 2021, 50(2): 141-147.
https://doi.org/10.3724/zdxbyxb-2021-0105
Infectious diseases are caused by infection of organism with pathogenic agents, which may lead to epidemics. Many infectious diseases such as syphilis, diphtheria, measles, and acquired immunodeficiency syndrome have specific and non-specific manifestations in the oral cavity. However, the same disease may have different oral manifestations in different patients clinically. We can apply the strategy of “three unusuals and one change” in clinical reasoning for diagnosis of infectious diseases with oral manifestations. The so-called “three unusuals” refer to unusual age, unusual location and unusual effect, and “one change” means the change from rare to common. In this article, we will give a comprehensive introduction about the oral manifestations of common communicable diseases and their diagnostic strategies.
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Research progress on Melkersson-Rosenthal syndrome
KUANG Wenjing,LUO Xiaobo,WANG Jiongke,ZENG Xin
J Zhejiang Univ (Med Sci), 2021, 50(2): 148-154.
https://doi.org/10.3724/zdxbyxb-2021-0103
Melkersson-Rosenthal syndrome (MRS) is a rare neuro-muco-cutaneous syndrome, which is characterized by recurrent orofacial swelling, recurrent facial paralysis and fissured tongue. It has a high prevalence in young adults. Up to now, the etiology of MRS is still not clear, it may related to infection, immune deficiency and hereditary factors. The pharmacological therapy and surgery are the main treatment. Corticosteroids seems to be the drug of choice for MRS patient, but the specific dosage and therapeutic effect have not yet been determined. Surgeries of lips provide excellent results in persistentlip edema MRS cases. This article reviews the research progress on MRS, focusing on its epidemiology, etiology, histopathological characteristics, clinical manifestations, classification, diagnostic criteria, differential diagnosis and treatment, to provide information for its early diagnosis and appropriate treatment.
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Clinical diagnosis of oral erosive and ulcerative diseases in children
LIU Chuanxia,CHEN Qianming
J Zhejiang Univ (Med Sci), 2021, 50(2): 155-161.
https://doi.org/10.3724/zdxbyxb-2021-0122
Mucosal disease is one of the most common oral cavity diseases in children, among which mucosal erosion and ulceration account for about 50%. Oral mucosal erosion and ulcer diseases in children are mostly acute with obvious pain, affecting speech, eating and swallowing. Some oral mucosal diseases are caused by infection and would result in epidemic among children. The onset age, sites, lesions size and quantity could vary, and some would have recurrence. The detailed medical history and comprehensive physical examination are necessary, some diseases can be diagnosed according to the medical history and clinical manifestations. If diagnosis can not be made, biopsy, blood test and immunofluorescence staining, immunohistochemistry, molecular biology detection, gene diagnosis, tuberculin test and other tests should be considered, and further investigation of systemic diseases should also be carried out if necessary. In some cases, multidisciplinary consultation should be sought. For those who still have no abnormal findings, therapeutic diagnosis can be tried out or secondary biopsy should be performed. In this article, the research progress of oral mucosal diseases in children is reviewed and our own clinical experiences of oral erosive and ulcerative diseases in children are summarized.
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TRAF6/ERK/p38 pathway is involved in interleukin-17-mediated autophagy to promote osteoclast precursor cell differentiation
SHEN Yeqi,WANG Zhongxiu,TAN Jingyi,ZHONG Jiahui,CHEN Lili
J Zhejiang Univ (Med Sci), 2021, 50(2): 162-170.
https://doi.org/10.3724/zdxbyxb-2021-0099
Objective: To investigate the effects of interleukin (IL)-17-mediated autophagy on the TNF receptor associated factor (TRAF6)/extracellular signal-regulated kinase (ERK)/p38 pathway and osteoclast differentiation. Methods:Mouse bone marrow-derived macrophages (BMM) were cultured with a medium containing 30?ng/mL macrophage colony stimulating factor and 50?ng/mL receptor activator of nuclear factor-kappa B ligard (RANKL), and IL-17 (0.01, 0.1, 1.0, 10?ng/mL) was added for intervention (IL-17 group). Tartrate-resistant acid phosphatase (TRAP) staining was used to observe TRAP positive multinucleated cells; phalloidin fluorescent staining was used to detect actin ring circumference; toluidine blue staining was used to analyze bone resorption lacuna formation. To further examine the mechanism of the effect of IL-17-mediated autophagy on the differentiation of osteoclasts, the control group used 50?ng/mL RANKL medium to culture mouse macrophage RAW264.7 cells, while the IL-17 group was treated with IL-17 (0.01, 0.1, 1.0, 10?ng/mL). Western blot was used to detect the expression of autophagy-related proteins Beclin-1, microtubule-associated protein 1 light chain 3 (LC3) and osteoclast-related proteins c-fos and nuclear factor of activated T cell 1 (NFATc1) after treatment with different concentrations of IL-17. The expression of LC3, NFATc1, TRAF6/ERK/p38 signaling pathway related proteins were detected in 1.0 ?ng/mL IL-17 and autophagy inhibitor 3-MA group. Results:The number of TRAP positive multinucleated cells, the circumference of the actin ring and the area of bone resorption lacuna in IL-17 group treated with IL-17 (0.01, 0.1, 1.0?ng/mL) were significantly higher than those in the control group. In IL-17 treated RAW264.7 cells, the expression of c-fos, NFATc1, Beclin-1, LC3, TRAF6, p-ERK, and p-p38 was all significantly up-regulated (all P <0.05). After treatment with the autophagy inhibitor 3-MA, the expression levels of LC3, NFATc1, TRAF6, p-ERK, and p-p38 all decreased significantly (all P <0.05). Conclusion:IL-17 can promote the expression of autophagy proteins and enhance the differentiation ability of osteoclast precursor cells, and the TRAF6/ERK/p38 signaling pathway may be involved in this process.
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Ca2+ mobilization and signaling pathways induced by Porphyromonas gingivalis rRgpB in human gingival fibroblast
ZHANG Diya,LU Kexin,LI Shenglai,WU Yanmin
J Zhejiang Univ (Med Sci), 2021, 50(2): 171-178.
https://doi.org/10.3724/zdxbyxb-2021-0109
Objective: To assess the Porphyromonas gingivalis (Pg) recombinant gingivalis gingipain R2 (rRgpB)-induced Ca2+ mobilization in human gingival fibroblast (HGF) mediated by protease-activated receptor (PAR) and its downstream signal transduction pathways. Methods: Flow cytometry was used to detect the expression of PAR in HGF. The proliferation of HGF was measured by CCK-8. The dynamic changes of intracellular Ca2+ concentration ([Ca2+]i) in HGF induced by rRgpB and the blocking effect of PAR-1 antagonist were observed by laser confocal microscopy. Western blot was performed to determine the phosphorylation levels of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) 1/2, p38 mitogen-activated protein kinase (p38 MAPK) and p65 in HGF. Results: PAR-1 and PAR-3 were expressed in HGF, and the rRgpB could promote the proliferation of HGF. rRgpB caused a transient increase in [Ca2+]i, which could be completely suppressed by vorapaxar, a PAR-1 antagonist. The phosphorylation levels of JNK, ERK1/2 and p65 were significantly up-regulated after the induction of rRgpB for 6?h and 12?h (all P<0.05), which was completely inhibited by vorapaxar. However, the phosphorylation level of p38 MAPK had no significant change after rRgpB stimulation.Conclusions: rRgpB causes an increase in [Ca2+]i in HGF mediated by PAR-1. JNK, ERK1/2 and nuclear factor-κB may be involved in intracellular signal transduction after PAR-1 activation.
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Effect of captopril pretreatment on the dentin bonding durability of self-etch adhesive
CHEN Yadong,LUO Qiaojie,SHU Chang,LI Xiaojun,LI Xiaodong
J Zhejiang Univ (Med Sci), 2021, 50(2): 179-186.
https://doi.org/10.3724/zdxbyxb-2021-0116
Objective:To investigate the effect of captopril on the dentin bonding durability of self-etch adhesive. Methods: Different concentrations of captopril ethanol solutions or captopril ethanol/water solutions were prepared to pretreat dentin as primer for the self-etch adhesives. The surface morphology of the dentin was observed with scanning electron microscopy (SEM). Based on the morphology analysis, the pretreatment condition was selected and two self-etch adhesives were employed to evaluate the improvement effect of the captopril pretreatment on the dentin bonding durability. Results: SEM showed that the pretreatment of captopril ethanol solutions and captopril ethanol/water solutions were able to remove the smear lay and partially expose collagen matrix. According to the SEM results, the pretreating condition of 0.15?g/mL captopril ethanol/water solution with the pretreating time of 30?s was selected for further dentin bonding study. For Clearfil SEBOND system, the immediate bonding strength increased from (30.80±4.70)?MPa to (37.48±3.20)?MPa?(P<0.05). After one-year aging, the bonding strength of the control group decreased markedly [(22.90±6.82)?MPa,P<0.05]; while the bonding strength of the captopril pretreated group kept steadily [(36.56±5.10)?MPa,P>0.05]. For Clearfil S3 BOND system, there was no significant difference in the immediate bonding strength between the experimental group [(34.70±4.07)?MPa] and the control group[(31.33±4.11)?MPa]. But after one-year aging, the bonding strength of the experimental group was higher than that of the control group [(32.36±3.58)?MPa and (21.43±6.27)?MPa,P<0.05].Conclusion: The pretreatment with captopril ethanol/water solution increases the dentin bonding strength of the self-etch adhesive systems and also improves the bonding durability.
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Establishment of an intelligent cervical vertebrae maturity assessment system based on cone beam CT data
FENG Xiaoyan,LU Shijuan,LI Yiming,LIN Jun
J Zhejiang Univ (Med Sci), 2021, 50(2): 187-194.
https://doi.org/10.3724/zdxbyxb-2021-0131
Objective:To establish an intelligent cervical vertebra maturity assessment system, and to evaluate the reliability and clinical value of the system. Methods: Sixty children aged 8-16?years were recruited in the study. Lateral cephalometric radiograph and cone beam CT (CBCT) were taken at the same period. Based on the CBCT data, the system automatically extracted the patient’s facial area through Otsu’s method, intercepted the sagittal plane by three-dimensional least squares method, captured the second to fourth cervical vertebrae by superpixel segmentation. And then selected points were marked automatically through morphological algorithm and manual method. Consistency test was performed on the two sets of data to compare the reliability of automated cervical morphology capture. According to the parameters of morphological identification, positioning and staging algorithms were designed to form the intelligent cervical vertebra maturity assessment system. The cervical vertebra maturity was also judged manually on the lateral cephalometric radiograph. The weighted Kappa test and the Gamma correlation coefficient were subsequently applied to evaluate the consistency and correlation. Results: The results showed that the cervical vertebra features automatically captured based on CBCT data had a high accuracy on the overall morphological recognition. In the prediction of 8 inflection points out of 13 points, there was no significant difference between automatic and manual method on both X and Y axes (all P>0.05). The assessment results of the cervical vertebra maturity of the intelligent system had strong consistency and correlation with the manual recognition results (weighted Kappa value=0.877, Gamma value=0.991, bothP<0.05).Conclusion:The intelligent cervical vertebrae maturity assessment system based on CBCT data established in this study presents reliable outcome and high degree of automation, indicating that the system may be used clinically.
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Clinical efficacy of counterclockwise rotating the functional occlusal plane using micro-implant anchorage
ZHANG Chenxing,XU Liqi,LIN Jun
J Zhejiang Univ (Med Sci), 2021, 50(2): 195-204.
https://doi.org/10.3724/zdxbyxb-2021-0123
Objective:To evaluate the therapeutic effect of using micro-implant anchorage (MIA) to rotate the functional occlusal plane (FOP) counterclockwise. Methods:Forty skeletal class Ⅱ high-angle patients who had completed orthodontic treatment were enrolled, including 20 patients treated with MIA orthodontic system (MIA group) and the other 20 patients treated with traditional sliding straight wire appliance (control group). Cephalometric measurements on the lateral cranial radiographs before and after treatment were performed, all acquired data were statistically analyzed with SPSS 26.0. Results:At the end of treatment, MIA group obtained better effect of FOP and mandibular plane counter-clockwise rotation than the control group. In the MIA group, the average change of FOP-frankfort horizontal plane (FH), FOP-SN and mandibular plane angle (MP-FH) angle was –4.5(–7.3, –3.7)°, (–4.6±3.3)° and –1.7(–3.0, –0.9)°, respectively. In the control group, the average change of FOP-FH, FOP-SN and MP-FH angle was –0.1(–4.1, 3.0)°, (–0.1±5.1)° and –0.4(–2.4, 0.7)°, respectively. There was significant difference between the change of the two groups (all P<0.05).Conclusion: Compared with the traditional sliding straight wire appliance, counterclockwise rotation of FOP can be more effectively reversed by using MIA orthodontic system, and the MP-FH can be reduced as well.
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Application of medical magnifying loupes in diagnosis of oral mucosal diseases
ZHANG Yuting,YUAN Peiyang,JIANG Han,QIU Xuemei,WANG Jiongke,LUO Xiaobo,DAN Hongxia,ZHOU Yu,ZENG Xin,JIANG Lu,CHEN Qianming
J Zhejiang Univ (Med Sci), 2021, 50(2): 205-211.
https://doi.org/10.3724/zdxbyxb-2021-0132
Objective: To evaluate the application of medical magnifying loupes in diagnosis of oral mucosal diseases. Methods: Twenty-four patients with plaque-type oral lichen planus or homogeneous oral leukoplakia were inspected by naked eyes or assistance with magnifying loupes. Histopathological results were used as the gold standard to evaluate the sensitivity, specificity and accuracy of the two methods in clinical diagnosis. Questionnaires were used to evaluate the subjective effect of magnifying loupes on the diagnosis efficiency of oral mucosal diseases and to explore the most suitable parameters for application. Results:The sensitivity, specificity and accuracy of medical magnifying loupes for the identification of plaque-type oral lichen planus and homogeneous oral leukoplakia were 94.74%, 100.00% and 95.83%, respectively, which were significantly higher than those of naked eye inspection (89.47%, 80.00% and 87.50%). The effective rate of magnifying loupes assisted diagnosis was 91.76% according to physicians’ subjective evaluation. The most suitable parameters were 3.5 times magnification and 400?mm working distance. Conclusion: The medical magnifying loupes can effectively improve the efficiency of the inspection and diagnosis of oral mucosal diseases, and have the characteristics of convenience and real-time. The recommended clinical parameters are 3.5 times magnification and 400?mm working distance.
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Research progress on tissue engineering in repairing temporo-mandibular joint
WANG Chenyu,WANG Yingnan,WANG Cunyi,SHI Jiejun,WANG Huiming
J Zhejiang Univ (Med Sci), 2021, 50(2): 212-221.
https://doi.org/10.3724/zdxbyxb-2021-0118
Temporomandibular joint osteoarthritis (TMJOA) is mainly manifested as perforation of temporomandibular joint disc (TMJD) and destruction of condylar osteochondral complex (COCC). In recent years, tissue engineering technology has become one of the effective strategies in repairing this damage. With the development of scaffold material technology, composite scaffolds have become an important means to optimize the performance of scaffolds with the combined advantages of natural materials and synthetic materials. The in situ gelling method with the minimally invasive concept can greatly solve the problems of surgical trauma and material anastomosis, which is beneficial to the clinical transformation of temporomandibular joint tissue engineering. Extracellular matrix scaffolds technology can solve the problem of scaffold source and maximize the simulation of the extracellular environment, which provides an important means for the transformation of temporomandibular joint tissue engineering to animal level. Due to the limitation of the source and amplification of costal chondrocytes, the use of mesenchymal stem cells from different sources has been widely used for temporomandibular joint tissue engineering. The fibrochondral stem cells isolated from surface layer of articular cartilage may provide one more suitable cell source. Transforming growth factor β superfamily, due to its osteochondrogenesis activity has been widely used in tissue engineering, and platelet-rich derivative as a convenient preparation of compound biological factor, gradually get used in temporomandibular joint tissue engineering. With the deepening of research on extracellular microenvironment and mechanical stimulation, mesenchymal stem cells, exosomes and stress stimulation are increasingly being used to regulate the extracellular microenvironment. In the future, the combination of complex bioactive factors and certain stress stimulation may become a trend in the temporomandibular joint tissue engineering research. In this article, the progress on tissue engineering in repairing COCC and TMJD, especially in scaffold materials, seed cells and bioactive factors, are reviewed, so as to provide information for future research design and clinical intervention.
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Immune mechanisms involved in the coexistence of oral lichen planus and autoimmune thyroid diseases
WANG Yahui,HAO Yilong,TANG Fan,CHEN Qianming
J Zhejiang Univ (Med Sci), 2021, 50(2): 222-228.
https://doi.org/10.3724/zdxbyxb-2021-0124
Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease with unclear etiology. Autoimmune thyroid diseases (AITD) is a type of autoimmune disease characterized by increased thyroid-specific antibodies. In recent years, more and more studies have found that the incidence of AITD is increased in OLP patients. The occurrence and development of OLP and AITD may be related to the expression of thyroid autoantigen in oral keratinocytes, the imbalance of thyroid hormone (Th)1/Th2 and Th17/Treg cell subsets, the abnormal quantity and function of follicular helper T cells and chemokines and the specific killing ability of CD8+ T cells to target cells. In this article, the possible immune mechanisms involved in the coexistence of OLP and AITD are reviewed to provide insights for the diagnosis, treatment and prevention of these two diseases from the perspective of immunology.
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Construction of PCSK9 point mutation rabbits using CRISPR/Cas9
YAN Kunning,ZHANG Ting,ZHA Yiwen,LIANG Jingyan,CHENG Yong
J Zhejiang Univ (Med Sci), 2021, 50(2): 229-238.
https://doi.org/10.3724/zdxbyxb-2021-0133
Objective:To establish a rabbit model of proprotein convertase subtilisin/kexin type9 (PCSK9) point mutation with CRISPR/Cas9 gene editing technique. Methods: According to the PubMed gene protein data, the PCSK9 protein functional regions of human and rabbit were analyzed by Blast. The 386S (Ser) amino acid functional region of human PCSK9 gene was homologous to the 485S of rabbit PCSK9 gene. Three small guide RNAs and one single-stranded donor oligonucleotide were designed according to the 485S base substitution position and sequence analysis of rabbit PCSK9 gene. The synthetic small guide RNAs, Cas9 mRNA and single-stranded donor oligonucleotide were co-injected into the cytoplasm of rabbit fertilized eggs and the embryos were transferred into the pregnant rabbits. PCR, TA cloning and off-target analysis were performed on the F0 rabbits to identify whether the PCSK9S386A mutation was successful. Results: Fifteen F0 rabbits were obtained. The sequencing results showed that one of them was PCSK9S386A point mutation homozygote and two of them were PCSK9S386A point mutation heterozygotes, and the mutation could be stably inherited. Conclusion: The rabbit model of PCSK9S386A point mutation was successfully constructed by CRISPR/Cas9 technique, which provides an animal model for exploring the molecular mechanism of impaired PCSK9 function and developing reliable and effective diagnosis and treatment measures.
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Postoperative serum triglyceride levels in predicting risk of new-onset diabetes mellitus in patients following liver transplantation
WU Yi,JIANG Weiliang,YANG Xiaojun,LI Wenhua,WAN Rong,LU Lungen,FAN Junwei,LU Zhanjun
J Zhejiang Univ (Med Sci), 2021, 50(2): 239-244.
https://doi.org/10.3724/zdxbyxb-2021-0114
Objective: To investigate the postoperative serum triglyceride (TG) levels in predicting the risk of new-onset diabetes mellitus (NODM) in patients following allogeneic liver transplantation. Methods: One hundred and forty three patients undergoing allogeneic liver transplantation in Shanghai General Hospital from July 2007 to July 2014 were enrolled in this study. The NODM developed in 33 patients after liver transplantation. The curve of dynamic TG levels in the early period after liver transplantation was generated. Independent risk factors of NODM were determined by univariate and multivariant logistic regression analyses. The clinical value of TG in predicting NODM was analyzed by area under the ROC curve (AUC). Results: Serum TG levels were gradually rising in the first week and then reached the plateau phase (stable TG, sTG) in patients after surgery. The sTG in NODM group were significantly higher than that in non-NODM group (Z=–2.31, P<0.05). Glucocorticoid therapy (OR=4.054, P<0.01), FK506 drug concentration in the first week after operation (OR=3.482, P<0.05) and sTG (OR=3.156, P<0.05) were independent risk factors of NODM. ROC curve analysis showed that the AUC of sTG in predicting NODM was 0.72.Conclusion: TG shows a gradual recovery process in the early period after liver transplantation, and the higher TG level in stable phase may significantly increase the risk of NODM in patients.
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Primary cilium and its role in tumorigenesis
MAO Hongmei,SUN Yi
J Zhejiang Univ (Med Sci), 2021, 50(2): 245-260.
https://doi.org/10.3724/zdxbyxb-2021-0048
The primary cilium, a sensory organelle that protrudes from the surface of most eukaryotic cells, receives and transduces various critical signals that are essential for normal development and homeostasis. Structural or functional disruption of primary cilia causes a number of human diseases, including cancer. Primary cilia has cross talks with cell cycle and it may act as a cell cycle checkpoint to suppress cancer development. Moreover, primary cilia has cross-regulation with autophagy, which may affect tumor progression. We then discuss the association of the primary cilia with several oncogenic signaling pathways, including Shh, Wnt, Notch and platelet-derived growth factor receptor (PDGFR). Since these signaling pathways are often over-activated in many types of human cancers, primary cilia are likely to play a role in the tumorigenesis by modulating these pathways. Finally, we summarize current progress on the role of cilia during tumorigenesis and the challenges that the cilia-cancer field faces.
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Research progress on the biomedical application of microalgae
REN Chaojie,ZHONG Danni,ZHOU Min
J Zhejiang Univ (Med Sci), 2021, 50(2): 261-266.
https://doi.org/10.3724/zdxbyxb-2021-0117
Microalgae is an easy-to-obtain natural biological material with many varieties and abundant natural reserves. Microalgae are rich in natural fluorescein, which can be used as a contrast agent for fluorescence imaging and photoacoustic imaging for medical imaging. With its active surface, microalgae can effectively adsorb functional molecules, metal elements, etc., and have good application prospects in the field of drug delivery. Microalgae can generate oxygen through photosynthesis to increase local oxygen concentration, reverse local hypoxia to enhance the efficacy of hypoxic tumors and promote wound healing. In addition, microalgae have good biocompatibility, and different administration methods have no obvious toxicity. This paper reviews the research progress on the biomedical application of microalgae in bioimaging, drug delivery, hypoxic tumor treatment, wound healing.
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Research progress on transient receptor potential melastatin 2 channel in nervous system diseases
YING Yingchao,JIANG Peifang
J Zhejiang Univ (Med Sci), 2021, 50(2): 267-276.
https://doi.org/10.3724/zdxbyxb-2021-0110
Transient receptor potential M2 (TRPM2) ion channel is a non-selective cationic channel that can permeate calcium ions, and plays an important role in neuroinflammation, ischemic reperfusion brain injury, neurodegenerative disease, neuropathic pain, epilepsy and other neurological diseases. In ischemic reperfusion brain injury, TRPM2 mediates neuronal death by modulating the different subunits of glutamate N-methyl-D-aspartic acid receptor in response to calcium/zinc signal. In Alzheimer’s disease, TRPM2 is activated by reactive oxygen species generated by β-amyloid peptide to form a malignant positive feedback loop that induces neuronal death and is involved in the pathological process of glial cells by promoting inflammatory response and oxidative stress. In epilepsy, the TRPM2-knockout alleviates epilepsy induced neuronal degeneration by inhibiting autophagy and apoptosis related proteins. The roles of TRPM2 channel in the pathogenesis of various central nervous system diseases and its potential drug development and clinical application prospects are summarized in this review.
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16 articles
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