1.Prognosis and regulation of inflammatory granulation tissue in tooth extraction socket
Wuyang ZHANG ; Yang XUE ; Kaijin HU
Journal of Prevention and Treatment for Stomatological Diseases 2024;32(10):737-745
Periodontitis and periapical periodontitis have a high incidence rate and often result in the progressive ab-sorption of alveolar bone.This is one of the main causes of tooth loosening and loss.Prolonged local inflammation leads to the proliferation of capillaries,fibroblasts,and inflammatory cells such as neutrophils and lymphocytes.This process results in the replacement of surrounding bone tissue with inflammatory granulation tissue.Traditionally,it has been ad-vocated that inflammatory granulation tissue is pathological and should be completely removed from the extraction sock-et to avoid complications such as bleeding,infection,and poor bone healing after tooth extraction.Although the regener-ative capacity of inflammatory granulation tissue is reduced,it can be enhanced by increasing the body's immunity or by eliminating pathogenic stimuli(such as tooth extraction and root canal treatment).As a result,the fibrous components in the inflammatory granulation tissue gradually increase,while infiltrating inflammatory cells gradually decrease.Ulti-mately,this transformation leads to the formation of reparative granulation tissue,followed by ossification.Furthermore,the use of granulation tissue from the tooth extraction socket for immediate implantation to facilitate wound closure or soft tissue reconstruction has yielded favorable clinical outcomes,and histological studies simultaneously confirmed the presence of mesenchymal stem cells within the inflammatory granulation tissue.Therefore,it is necessary to reconsider the traditional belief that inflammatory granulation tissue must be completely removed.Given the potential of inflamma-tory granulation tissue to undergo osteogenic transformation under appropriate interventions,regulating the transforma-tion of inflammatory granulation tissue into reparative granulation tissue with osteogenic potential represents a novel strategy for the regenerative treatment of dental alveolar inflammatory lesions.This approach holds broad clinical appli-cation prospects and is an important research direction for the future.Reactive oxygen species,NOD-like receptor pro-tein 3,and matrix metalloproteinase K are key regulatory factors involved in the transformation of inflammatory granula-tion tissue into reparative granulation tissue.Furthermore,bone morphogenetic protein 2 and vascular endothelial growth factor are key regulatory factors involved in the osteogenic regeneration of reparative granulation tissue.Howev-er,the molecular mechanisms of these regulatory factors remain unclear;therefore,elucidating their molecular mecha-nisms will help identify suitable targets for promoting the regeneration of dental alveolar inflammatory lesions.Further-more,this will contribute to the development of related biological treatment technologies and drugs,which may ultimate-ly provide a more minimally invasive and effective treatment for inflammatory lesions of alveolar bone.However,it is im-portant to note that research in this field is still in its early stages.There is still considerable progress to be made before clinical translation and application can be achieved.
2.Strolling through the glorious years of Alveolar Surgery, bravely stepping onto the path of practice and innovation
Yiming WANG ; Yang XUE ; Jihong ZHAO ; Jian PAN ; Duohong ZOU ; Nianhui CUI ; Wei ZHANG ; Qizhang WANG ; Zhizheng LI ; Yuqiong ZHOU ; Kaijin HU
Chinese Journal of Stomatology 2024;59(4):301-311
This article summarizes and organizes relevant publications in journals, along with a review of medical history, systematically summarizing the development process of dental alveolar surgery in China. The initial establishment phase (1935—1952) marked the starting point of Chinese Alveolar Surgery. Despite the impact of wars, it laid the foundation for subsequent research and practice. During the early development phase (1953—1966), the "Chinese Journal of Stomatology" was founded, which promoted the development of Alveolar Surgery. Research focused on tooth extraction methods and complications. Tooth Transplantation and Preprosthetic Surgery gradually began to take off. The stagnant phase (1967—1977) occurred due to the interruption of international exchanges, leading to an almost complete halt in the development of Alveolar Surgery. Entering the rapid catch-up phase (1978—1985), Alveolar Surgery scholars in China began striving to overcome the stagnation of the previous decade. While some progress was made, no significant innovative achievements emerged. In the scientific development phase (1986—2010), clinical research, basic experiments, and paper writing in modern Chinese Alveolar Surgery began to adhere to scientific standards with the rise of experimental medicine. The exploration and innovation stage (2011—2023) is the current development phase, during which Chinese Aveolar Surgery has reached its peak, making substantial progress in technology, clinical practices, and basic research, gradually reaching or even surpassing international advanced levels. Looking back at the development history in China, we can find the wisdom and hard work of the older generation of Alveolar Surgery scholars. However, contemporary challenges and issues, such as standardizing technology, promoting clinical practices, and talent cultivation, need to be addressed by present-day Alveolar Surgery professionals as they forge ahead.
3.Discussion and evaluation of several issues concerning the classification of impacted third molars
Sen JIA ; Yang XUE ; Kaijin HU
Chinese Journal of Stomatology 2024;59(8):759-763
The classification of impacted third molars is important in clinical diagnosis and surgical selection. At present, the common clinical impacted third molar classification is different in the maxillary and mandibular classification criteria. Through the review and analysis of various classification methods of impacted third molar, this paper proposes a more comprehensive and unified classification proposal for the classification of impacted third molar, in order to form a widely accepted application classification method.
4.Deciphering the fate of granulation tissue in the human inflammatory alveolar microenvironment using single-cell RNA sequencing
Yuan LI ; Yang XUE ; Yu ZHANG ; Kaijin HU
Chinese Journal of Stomatology 2024;59(8):804-809
Objective:To investigate the cellular composition and heterogeneity of granulation tissue in human alveolar sockets and construct single-cell transcriptomic maps to elucidate the potential outcomes of natural resolution in the inflammatory microenvironment.Methods:Granulation tissues from 12 alveolar sockets undergoing tooth extraction due to periodontitis and scheduled for delayed site preservation or autologous tooth transplantation were collected in the Department of Oral and Maxillofacial Surgery, School of Stomatology,The Fourth Military Medical University from September 2022 to August 2023. This study used HE staining and single-cell RNA sequencing (scRNA-seq) to observe the cellular composition and morphological changes of different types of granulation tissues. This approach enabled us to identify cellular sequence variations in the inflammatory dental alveolar granulation tissue within specific microenvironments, construct single-cell atlases for different types of human dental alveolar granulation tissues, and explore the spatiotemporal patterns of cell type distribution and key gene changes during the resolution process of inflammatory granulation tissue.Results:HE staining revealed extensive infiltration of inflammatory cells in the dental alveolar inflammatory granulation tissue. After allowing the inflammatory granulation tissue to naturally resolve for three weeks, its histological morphology was essentially consistent with that of reparative granulation tissue. ScRNA-seq captured a total of 20 448 cells from granulation tissues, and the gene expression quantification analysis revealed total gene counts of 33 835 for inflammatory granulation tissue, 36 058 for naturally resolved granulation tissue, and 34 719 for reparative granulation tissue. At the single-cell level, granulation tissue was annotated into ten cell subgroups, including vascular endothelial cells, mesenchymal stem cells, and fibroblasts. Differences were observed in the proportion of cell compositions between inflammatory and naturally resolved granulation tissues. Pseudo-temporal analysis illustrated two main outcomes in tissue resolution and healing, involving immune responses and angiogenesis. Among these, genes associated with inflammation regulation and immune response, such as Igbp5, Zfp36, and Hspa1b, as well as genes involved in extracellular matrix secretion and the formation of vessels and fibers such as Timp3, Postn, and Rgs5, showed significant differences in expression between the two types of granulation tissues.Conclusions:Inflammatory granulation tissue exhibits heterogeneity in cell composition, gene expression, and biological functions compared to naturally resolved granulation tissue. When the inflammatory granulation tissue in the alveolar socket is left undisturbed to undergo natural resolution, it displays a cellular composition similar to that of reparative granulation tissue at both the histological and single-cell levels. Moreover, it modulates the inflammatory response and the healing process through immune reactions and tissue remodeling.
5.Study of Ctsk knockout regulating type H blood vessel formation and tooth extraction socket healing in mice
Wuyang ZHANG ; Dengke LI ; Yiming WANG ; Yuan LI ; Yuzhe CHEN ; Xueni ZHENG ; Hongzhi ZHOU ; Kaijin HU ; Yang XUE
Journal of Practical Stomatology 2024;40(3):330-336
Objective:To study the effects of cathepsin K(CTSK)on the healing process of tooth extraction socket and type H blood vessel angiogenesis in mice.Methods:Ctsk knockout(Ctsk-/-)mice were generated by CRISPR/Cas9 technology,and genotype sequen-cing,general observation,Micro-CT and immunohistochemistry were performed to confirm successful knockout of Ctsk.Then 8 week-old WT and Ctsk-/-mice were used to establish the tooth extraction modle by extracting the left maxillary first molars,and the mice were sac-rificed at the day 7,10,14,21,28 and 35 respectively(n=3)after tooth extraction.Then samples were subjected to stereo microscope and Micro-CT examination.Immunofluorescence staining was used to study the effect of Ctsk knockout on type H blood vessel angiogene-sis.Results:Ctsk knockout did not affect the soft tissue healing of tooth extraction socket,but significantly promoted the bone healing process,and Ctsk deficency significantly enhanced type H blood vessel angiogenesis in the tooth extraction socket.Conclusion:Ctsk knockout can enhance type H vessel angiogenesis,and promote bone healing process of tooth extraction socket in mice.
6.Research progress on genetic control of host susceptibility to tuberculosis.
Journal of Zhejiang University. Medical sciences 2023;51(6):679-690
The "Lübeck disaster", twins studies, adoptees studies, and other epidemiological observational studies have shown that host genetic factors play a significant role in determining the host susceptibility to Mycobacterium tuberculosis infection and pathogenesis of tuberculosis. From linkage analyses to genome-wide association studies, it has been discovered that human leucocyte antigen (HLA) genes as well as non-HLA genes (such as SLC11A1, VDR, ASAP1 as well as genes encoding cytokines and pattern recognition receptors) are associated with tuberculosis susceptibility. To provide ideas for subsequent studies about risk prediction of MTB infection and the diagnosis and treatment of tuberculosis, we review the research progress on tuberculosis susceptibility related genes in recent years, focusing on the correlation of HLA genes and non-HLA genes with the pathogenesis of tuberculosis. We also report the results of an enrichment analysis of the genes mentioned in the article. Most of these genes appear to be involved in the regulation of immune system and inflammation, and are also closely related to autoimmune diseases.
Humans
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Genome-Wide Association Study
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Tuberculosis/genetics*
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Gene Expression Regulation
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Cytokines/genetics*
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Autoimmune Diseases
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Mycobacterium tuberculosis/genetics*
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Genetic Predisposition to Disease
7.New progress in the pathogenesis of traumatic temporomandibular joint ankylosis
HU Kaijin ; MA Zhen ; WANG Yiming ; DENG Tiange
Journal of Prevention and Treatment for Stomatological Diseases 2021;29(12):793-800
Traumatic temporomandibular joint ankylosis refers to fibrous or bony fusion between the condyle and the glenoid fossa. It can cause problems with mouth-opening limitations, mastication difficulties, obstructive sleep apnea and hypopnea syndrome. When traumatic temporomandibular joint ankylosis occurs during childhood, it can cause facial asymmetry, micrognathia, and malocclusion, which significantly affect the physical and mental health. Once temporomandibular joint ankylosis occurs, it will be refractory and recurrent. The pathogenesis of temporomandibular joint ankylosis has not been completely elucidated and has always been a research hotspot in the oral and maxillofacial fields. In this paper, worldwide research was conducted, and the pathogenesis of traumatic temporomandibular joint ankylosis was clarified, such as “damage of condyle”,“disc displacement or rupture”,“damage to the glenoid fossa” and “lateral pterygoid muscle distraction”. The relative pathogenesis hypotheses were summarized, such as “hematoma organization” and “lateral pterygoid muscle distraction osteogenesis”. The related pathogenesis of traumatic temporomandibular joint ankylosis was discussed based on the latest cytology and molecular biology research.
8.Expert consensus on the treatment of oral and maxillofacial space infections
Yunpeng LI ; Bing SHI ; Junrui ZHANG ; Yanpu LIU ; Guofang SHEN ; Chuanbin GUO ; Chi YANG ; Zubing LI ; Zhiguang ZHANG ; Huiming WANG ; Li LU ; Kaijin HU ; Ping JI ; Biao XU ; Wei ZHANG ; Jingming LIU ; Zhongcheng GONG ; Zhanping REN ; Lei TIAN ; Hua YUAN ; Hui ZHANG ; Jie MA ; Liang KONG
Chinese Journal of Stomatology 2021;56(2):136-144
Oral and maxillofacial space infections (OMSI) are common diseases of the facial region involving fascial spaces. Recently, OMSI shows trends of multi drug-resistance, severe symptoms, and increased mortality. OMSI treatment principles need to be updated to improve the cure rate. Based on the clinical experiences of Chinese experts and with the incorporation of international counterparts′ expertise, the principles of preoperative checklist, interpretation of examination results, empirical medication principles, surgical treatment principles, postoperative drainage principles, prevention strategies of wisdom teeth pericoronitis-related OMSI, blood glucose management, physiotherapy principles, Ludwig′s angina treatment and perioperative care were systematically summarized and an expert consensus on the diagnosis and treatment of OMSI was reached. The consensus aims to provide criteria for the diagnosis and treatment of OMSI in China so as to improve the level of OMSI treatment.
9.Management of corona virus disease-19 (COVID-19): the Zhejiang experience.
Kaijin XU ; Hongliu CAI ; Yihong SHEN ; Qin NI ; Yu CHEN ; Shaohua HU ; Jianping LI ; Huafen WANG ; Liang YU ; He HUANG ; Yunqing QIU ; Guoqing WEI ; Qiang FANG ; Jianying ZHOU ; Jifang SHENG ; Tingbo LIANG ; Lanjuan LI
Journal of Zhejiang University. Medical sciences 2020;49(1):0-0
The current epidemic situation of corona virus disease-19 (COVID-19) still remained severe. As the National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital of Zhejiang University School of Medicine is the primary medical care center for COVID-19 inZhejiang Province. Based on the present expert consensus carried out by National Health Commission and National Administration of Traditional Chinese Medicine, our team summarized and established an effective treatment strategy centered on "Four-Anti and Two-Balance" for clinical practice. The "Four-Anti and Two-Balance"strategy included antivirus, anti-shock, anti-hyoxemia, anti-secondary infection, and maintaining of water, electrolyte and acid base balance and microecological balance. Meanwhile, integrated multidisciplinarypersonalized treatment was recommended to improve therapeutic effect. The importance of early viralogical detection, dynamic monitoring of inflammatory indexes and chest radiograph was emphasized in clinical decision-making. Sputum was observed with the highest positive rate of RT-PCR results. Viral nucleic acids could be detected in10% patients'blood samples at acute periodand 50% of patients had positive RT-PCR results in their feces. We also isolated alive viral strains from feces, indicating potential infectiousness of feces.Dynamic cytokine detection was necessary to timely identifyingcytokine storms and application of artificial liver blood purification system. The "Four-Anti and Two-Balance"strategyeffectively increased cure rate and reduced mortality. Early antiviral treatment could alleviate disease severity and prevent illness progression, and we found lopinavir/ritonavir combined with abidol showed antiviraleffects in COVID-19. Shock and hypoxemia were usually caused by cytokine storms. The artificial liver blood purification system could rapidly remove inflammatory mediators and block cytokine storm.Moreover, it also favoredthe balance of fluid, electrolyte and acid-base and thus improved treatment efficacy in critical illness. For cases of severe illness, early and also short periods of moderate glucocorticoid was supported. Patients with oxygenation index below 200 mmHg should be transferred to intensive medical center. Conservative oxygen therapy was preferred and noninvasive ventilation was not recommended. Patients with mechanical ventilation should be strictly supervised with cluster ventilator-associated pneumonia prevention strategies. Antimicrobial prophylaxis should be prescribed rationally and was not recommended except for patients with long course of disease, repeated fever and elevated procalcitonin (PCT), meanwhile secondary fungal infection should be concerned.Some patients with COVID-19 showed intestinal microbialdysbiosis with decreasedprobiotics such as and . Nutritional and gastrointestinal function should be assessed for all patients.Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infection due to bacterial translocation. Anxiety and fear were common in patients with COVID-19. Therefore, we established dynamic assessment and warning for psychological crisis. We also integrated Chinese medicine in treatment to promote disease rehabilitation through classification methods of traditional Chinese medicine. We optimized nursing process for severe patients to promote their rehabilitation. It remained unclear about viral clearance pattern after the SARS-CoV-2 infection. Therefore, two weeks' quarantine for discharged patients was required and a regular following up was also needed.The Zhejiang experience above and suggestions have been implemented in our center and achieved good results. However, since COVID-19 was a newly emerging disease, more work was warranted to improve strategies of prevention, diagnosis and treatment for COVID-19.
10.Management of COVID-19: the Zhejiang experience.
Kaijin XU ; Hongliu CAI ; Yihong SHEN ; Qin NI ; Yu CHEN ; Shaohua HU ; Jianping LI ; Huafen WANG ; Liang YU ; He HUANG ; Yunqing QIU ; Guoqing WEI ; Qiang FANG ; Jianying ZHOU ; Jifang SHENG ; Tingbo LIANG ; Lanjuan LI
Journal of Zhejiang University. Medical sciences 2020;49(2):147-157
The current epidemic situation of coronavirus disease 2019 (COVID-19) still remained severe. As the National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital of Zhejiang University School of Medicine is the primary medical care center for COVID-19 in Zhejiang province. Based on the present expert consensus carried out by National Health Commission and National Administration of Traditional Chinese Medicine, our team summarized and established an effective treatment strategy centered on "Four-Anti and Two-Balance" for clinical practice. The "Four-Anti and Two-Balance" strategy included antivirus, anti-shock, anti-hyoxemia, anti-secondary infection, and maintaining of water, electrolyte and acid base balance and microecological balance. Meanwhile, integrated multidisciplinary personalized treatment was recommended to improve therapeutic effect. The importance of early viralogical detection, dynamic monitoring of inflammatory indexes and chest radiograph was emphasized in clinical decision-making. Sputum was observed with the highest positive rate of RT-PCR results. Viral nucleic acids could be detected in 10%patients' blood samples at acute period and 50%of patients had positive RT-PCR results in their feces. We also isolated alive viral strains from feces, indicating potential infectiousness of feces.Dynamic cytokine detection was necessary to timely identifying cytokine storms and application of artificial liver blood purification system. The "Four-Anti and Two-Balance" strategy effectively increased cure rate and reduced mortality. Early antiviral treatment could alleviate disease severity and prevent illness progression, and we found lopinavir/ritonavir combined with abidol showed antiviral effects in COVID-19. Shock and hypoxemia were usually caused by cytokine storms. The artificial liver blood purification system could rapidly remove inflammatory mediators and block cytokine storm.Moreover, it also favored the balance of fluid, electrolyte and acid-base and thus improved treatment efficacy in critical illness. For cases of severe illness, early and also short period of moderate glucocorticoid was supported. Patients with oxygenation index below 200 mmHg should be transferred to intensive medical center. Conservative oxygen therapy was preferred and noninvasive ventilation was not recommended. Patients with mechanical ventilation should be strictly supervised with cluster ventilator-associated pneumonia prevention strategies. Antimicrobial prophylaxis was not recommended except for patients with long course of disease, repeated fever and elevated procalcitonin (PCT), meanwhile secondary fungal infection should be concerned.Some patients with COVID-19 showed intestinal microbial dysbiosis with decreased probiotics such as and , so nutritional and gastrointestinal function should be assessed for all patients.Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infection due to bacterial translocation. Anxiety and fear were common in patients with COVID-19. Therefore,we established dynamic assessment and warning for psychological crisis. We also integrated Chinese medicine in treatment to promote disease rehabilitation through classification methods of traditional Chinese medicine. We optimized nursing process for severe patients to promote their rehabilitation. It remained unclear about viral clearance pattern after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, two weeks' quarantine for discharged patients was required and a regular following up was also needed.The Zhejiang experience and suggestions have been implemented in our center and achieved good results. However, since COVID-19 was a newly emerging disease, more work was warranted to improve strategies of prevention, diagnosis and treatment for COVID-19.
Betacoronavirus
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isolation & purification
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China
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epidemiology
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Coronavirus Infections
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diagnosis
;
epidemiology
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therapy
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virology
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Disease Management
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Early Diagnosis
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Feces
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virology
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Humans
;
Pandemics
;
Pneumonia, Viral
;
diagnosis
;
epidemiology
;
therapy
;
virology
;
Sputum
;
virology


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