1.Effect Analysis of Different Interventions to Improve Neuroinflammation in The Treatment of Alzheimer’s Disease
Jiang-Hui SHAN ; Chao-Yang CHU ; Shi-Yu CHEN ; Zhi-Cheng LIN ; Yu-Yu ZHOU ; Tian-Yuan FANG ; Chu-Xia ZHANG ; Biao XIAO ; Kai XIE ; Qing-Juan WANG ; Zhi-Tao LIU ; Li-Ping LI
Progress in Biochemistry and Biophysics 2025;52(2):310-333
Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.
2.Quality evaluation of Xinjiang Rehmannia glutinosa and Rehmannia glutinosa based on fingerprint and multi-component quantification combined with chemical pattern recognition.
Pan-Ying REN ; Wei ZHANG ; Xue LIU ; Juan ZHANG ; Cheng-Fu SU ; Hai-Yan GONG ; Chun-Jing YANG ; Jing-Wei LEI ; Su-Qing ZHI ; Cai-Xia XIE
China Journal of Chinese Materia Medica 2025;50(16):4630-4640
The differences in chemical quality characteristics between Xinjiang Rehmannia glutinosa and R. glutinosa were analyzed to provide a theoretical basis for the introduction and quality control of R. glutinosa. In this study, the high performance liquid chromatography(HPLC) fingerprints of 6 batches of Xinjiang R. glutinosa and 10 batches of R. glutinosa samples were established. The content of iridoid glycosides, phenylethanoid glycosides, monosaccharides, oligosaccharides, and polysaccharides in Xinjiang R. glutinosa and R. glutinosa was determined by high performance liquid chromatography-diode array detection(HPLC-DAD), high performance liquid chromatography-evaporative light scattering detection(HPLC-ELSD), and ultraviolet-visible spectroscopy(UV-Vis). The determination results were analyzed with by chemical pattern recognition and entropy weight TOPSIS method. The results showed that there were 19 common peaks in the HPLC fingerprints of the 16 batches of R. glutinosa, and catalpol, aucubin, rehmannioside D, rehmannioside A, hydroxytyrosol, leonuride, salidroside, cistanoside A, and verbascoside were identified. Hierarchical cluster analysis(HCA) and principal component analysis(PCA) showed that Qinyang R. glutinosa, Mengzhou R. glutinosa, and Xinjiang R. glutinosa were grouped into three different categories, and eight common components causing the chemical quality difference between Xinjiang R. glutinosa and R. glutinosa in Mengzhou and Qinyang of Henan province were screened out by orthogonal partial least squares discriminant analysis(OPLS-DA). The results of content determination showed that there were glucose, sucrose, raffinose, stachyose, polysaccharides, and nine glycosides in Xinjiang R. glutinosa and R. glutinosa samples, and the content of catalpol, rehmannioside A, leonuride, cistanoside A, verbascoside, sucrose, and glucose was significantly different between Xinjiang R. glutinosa and R. glutinosa. The analysis with entropy weight TOPSIS method showed that the comprehensive quality of R. glutinosa in Mengzhou and Qinyang of Henan province was better than that of Xinjiang R. glutinosa. In conclusion, the types of main chemical components of R. glutinosa and Xinjiang R. glutinosa were the same, but their content was different. The chemical quality of R. glutinosa was better than Xinjiang R. glutinosa, and other components in R. glutinosa from two producing areas and their effects need further study.
Rehmannia/classification*
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Drugs, Chinese Herbal/chemistry*
;
Chromatography, High Pressure Liquid/methods*
;
Quality Control
3.Mechanism of inhibiting miR-34a-5p expression and promoting bone growth in mouse brain tissue by Semen Ziziphi Spinosae extract.
Yuan-Yuan PEI ; Yan XIE ; Na YIN ; Wen-Long MA ; Wei-Peng XING ; Gui-Zhi WANG ; Qing-Feng WANG
China Journal of Orthopaedics and Traumatology 2025;38(10):1061-1070
OBJECTIVE:
To explore the mechanism by which the extract of Semen Ziziphi Spinosae extract promotes bone growth in mice by modulation of the expression of miR-34a-5p in brain tissue.
METHODS:
Mice were assigned to four experimental groups:a normal control group, a drug administration group (receiving 0.320 mg·g-1 body weight of Semen Ziziphi Spinosae extract via intragastric administration), a positive control group (receiving 0.013 mg·g-1 body weight of jujube seed saponin via intragastric administration), and a combination group administration with Semen Ziziphi Spinosae extract plus a 5-hydroxytryptamine 2A receptor (5-HT2AR) agonist (intragastric administration of Semen Ziziphi Spinosae extract combined with intracerebroventricular injection of 8 μg P-MPPF per mice for the final three days of the experiment). Following a 20-day administration period, the effects of the interventions on bone growth, serum growth hormone (GH) levels, and 5-HT2AR expression in brain tissue were evaluated. MicroRNAs (miRNAs) that were differentially expressed in the brain tissues of mice exhibiting bone growth induced by Semen Ziziphi Spinosae extract, as compared to those in normal mice, were identified using a gene chip approach. The interaction between miR-34a-5p and 5-HT2AR was subsequently validated through quantitative reverse transcription polymerase chainreaction (RT-qPCR) and dual-luciferase reporter gene assays. Subsequently, by utilizing the miR-34a-5p inhibitor group and mimics group, along with the normal control group, the drug administration group, the positive control group, and the drug administration combined with miR-34a-5p inhibitor group, the variations in 5-HT2AR expression in mouse brain tissue across all groups were examined, and the binding activity of 5-hydroxytryptamine (5-HT) to the 5-hydroxytryptamine 1A receptor (5-HT1AR) in mice was assessed.
RESULTS:
The body lengths of the normal control group and the drug administration group were(8.9±0.3) and(10.4±0.4) cm;femur lengths were (8.5±0.3) and (9.1±0.5) mm;tibia lengths were (10.7±0.3) and (11.2±0.4) mm, respectively. The contents of GH levels were (58.6±8.2) and (72.9±6.1) ng·ml-1;and the contents of 5-HT2AR were (32.0±5.0) and (21.9± 5.5) ng·ml-1, respectively. Compared with the normal control group, the drug administration group promoted the growth of body length, femur, and tibia in mice, and increased GH secretion, showing statistically significant differences (P<0.05). Additionally, it significantly reduced the content of 5-HT2AR in brain tissue, with statistical significance (P<0.01). The gene chip analysis identified a total of 16 differentially expressed miRNAs, of which 13 were up-regulated and 3 were down-regulated. Bioinformatics analysis predicted that the up-regulated miR-34a-5p could regulate the expression of 5-HT2AR, a prediction that was confirmed through a dual-luciferase reporter gene assay, demonstrating a direct regulatory interaction between the two. Furthermore, in vivo experiments in mice revealed that overexpression and silencing of miR-34a-5p resulted in corresponding changes in the expression levels of 5-HT2AR in brain tissues/cells, as well as in the binding activity between 5-HT and 5-HT1AR.
CONCLUSION
The Semen Ziziphi Spinosae extract promotes animal bone growth by enhancing miR-34a-5p expression in brain tissue, downregulating the expression level of 5-HT2AR, improving the binding activity between 5-HT and 5-HT1AR, and extending slow-wave sleep duration, thereby stimulating GH secretion.
Animals
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MicroRNAs/metabolism*
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Mice
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Male
;
Brain/metabolism*
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Ziziphus/chemistry*
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Bone Development/drug effects*
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Drugs, Chinese Herbal/pharmacology*
;
Plant Extracts/pharmacology*
4.Clinical efficacy of endocrinotherapy combined with Shenqi Pills on patients with hormone-sensitive prostate cancer.
Yu-Hong XIE ; Gang YI ; Xiao-Wen YI ; Tong-Lin SUN ; Qun-Fang LIN ; Jun ZHOU ; Xin-Jun LUO ; Fang-Zhi FU ; Biao WANG ; Qin-Zheng WANG ; Lie ZHANG ; Yang YANG ; Rui-Song GAO ; Qing ZHOU
National Journal of Andrology 2025;31(4):341-348
OBJECTIVE:
The aim of this study is to explore the clinical efficacy and safety of endocrinotherapy combined with Shenqi Pills on hormone-sensitive prostate cancer (HSPC).
METHODS:
Eighty patients who were diagnosed with HSPC and renal-yang deficiency at the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine and the Hospital of Traditional Chinese Medicine of Mayang Miao Autonomous County from 1st April 2021 to 30th April 2024 were randomly divided into 2 groups. The patients in the control group were treated with androgen deprivation therapy (ADT). And the patients in treatment group were treated with Shenqi Pills orally on the basis of the control group. The baseline data of the two groups were analyzed. After 36 months of treatment, the differences between the two groups were compared in terms of overall survival (OS), prostate-specific antigen (PSA) level, PSA response rate, Functional Assessment Scale for Prostate Cancer Therapy (FACT-P), Chinese medicine evidence scores, testosterone level and safety.
RESULTS:
A total of 80 study subjects were included in this study, including 42 cases in the treatment group and 38 cases in the control group. There was no statistical difference in the baseline data between the two groups before treatment (P>0.05). At the end of the observation period, a statistically significant difference in OS was found in the treatment group compared to the control group in the subgroup of patients with a disease duration ranged of 0-6 months (P<0.05). There was no statistically significant difference in PSA levels in the treatment group at 3 months (P>0.05). And the differences in the proportion of PSA50 (98.1% vs 91.4%), PSA90 (92.9% vs 84.6%) and the proportion of decrease in PSA (56.7% vs 33.8%) in the treatment group were found compared to those in the control group after 6 months of tre atment. After 12 months of treatment, the scores of FACT-4 and renal-yang deficiency in the treatment group were (95.28±7.93) and (15.73±5.70) respectively, compared to the scores in the control group ([85.46±10.12] and [18.20±4.27] (P<0.05). However, there was no significant difference in serum testosterone ([0.60±0.24] nmol/L vs [1.09±2.10] nmol/L) between the two groups (P>0.05). After 24 months of treatment, there were significant differences in in the FACT-4 total score ([97.95±7.54] vs [80.33±8.58]), renal-yang deficiency syndrome score ([14.64±5.15] vs [24.94±8.75]) between the treatment group and the control group (P<0.05). However, there was no significant difference in serum testosterone ( [0.73±1.01] nmol/L vs [0.59±0.25] nmol/L) between the two groups (P> 0.05). Better therapeutic results were showed in the treatment group in terms of total FACT-P score, physical situation score, social and family situation score, emotional state score, functional state score, additional score and renal-yang deficiency symptom score (P<0.05). After treatment, there was no serious adverse reaction in the course of treatment, and no obvious abnormality was found in the liver and kidney function of the patients from two groups.
CONCLUSION
Endocrinotherapy combined with Shenqi Pills is safe and effective in HSPC and can reduce the risk of death in HSPC patients, and the earlier the intervention, the longer the overall survival of the patients. In addition, this treatment regimen can increase the PSA response rate, improve patients' quality of life, and reduce the renal-yang deficiency syndrome score without the risk of elevating serum testosterone levels.
Humans
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Male
;
Drugs, Chinese Herbal/therapeutic use*
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Prostatic Neoplasms/drug therapy*
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Androgen Antagonists/therapeutic use*
;
Prostate-Specific Antigen/blood*
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Aged
;
Middle Aged
;
Treatment Outcome
;
Testosterone
5.Expert consensus on apical microsurgery.
Hanguo WANG ; Xin XU ; Zhuan BIAN ; Jingping LIANG ; Zhi CHEN ; Benxiang HOU ; Lihong QIU ; Wenxia CHEN ; Xi WEI ; Kaijin HU ; Qintao WANG ; Zuhua WANG ; Jiyao LI ; Dingming HUANG ; Xiaoyan WANG ; Zhengwei HUANG ; Liuyan MENG ; Chen ZHANG ; Fangfang XIE ; Di YANG ; Jinhua YU ; Jin ZHAO ; Yihuai PAN ; Shuang PAN ; Deqin YANG ; Weidong NIU ; Qi ZHANG ; Shuli DENG ; Jingzhi MA ; Xiuping MENG ; Jian YANG ; Jiayuan WU ; Yi DU ; Junqi LING ; Lin YUE ; Xuedong ZHOU ; Qing YU
International Journal of Oral Science 2025;17(1):2-2
Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards*
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Humans
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Apicoectomy
;
Contraindications, Procedure
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Tooth Apex/diagnostic imaging*
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Postoperative Complications/prevention & control*
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Consensus
;
Treatment Outcome
6.Expert consensus on pulpotomy in the management of mature permanent teeth with pulpitis.
Lu ZHANG ; Chen LIN ; Zhuo CHEN ; Lin YUE ; Qing YU ; Benxiang HOU ; Junqi LING ; Jingping LIANG ; Xi WEI ; Wenxia CHEN ; Lihong QIU ; Jiyao LI ; Yumei NIU ; Zhengmei LIN ; Lei CHENG ; Wenxi HE ; Xiaoyan WANG ; Dingming HUANG ; Zhengwei HUANG ; Weidong NIU ; Qi ZHANG ; Chen ZHANG ; Deqin YANG ; Jinhua YU ; Jin ZHAO ; Yihuai PAN ; Jingzhi MA ; Shuli DENG ; Xiaoli XIE ; Xiuping MENG ; Jian YANG ; Xuedong ZHOU ; Zhi CHEN
International Journal of Oral Science 2025;17(1):4-4
Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans
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Calcium Compounds/therapeutic use*
;
Consensus
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Dental Pulp
;
Dentition, Permanent
;
Oxides/therapeutic use*
;
Pulpitis/therapy*
;
Pulpotomy/standards*
7.Expert consensus on intentional tooth replantation.
Zhengmei LIN ; Dingming HUANG ; Shuheng HUANG ; Zhi CHEN ; Qing YU ; Benxiang HOU ; Lihong QIU ; Wenxia CHEN ; Jiyao LI ; Xiaoyan WANG ; Zhengwei HUANG ; Jinhua YU ; Jin ZHAO ; Yihuai PAN ; Shuang PAN ; Deqin YANG ; Weidong NIU ; Qi ZHANG ; Shuli DENG ; Jingzhi MA ; Xiuping MENG ; Jian YANG ; Jiayuan WU ; Lan ZHANG ; Jin ZHANG ; Xiaoli XIE ; Jinpu CHU ; Kehua QUE ; Xuejun GE ; Xiaojing HUANG ; Zhe MA ; Lin YUE ; Xuedong ZHOU ; Junqi LING
International Journal of Oral Science 2025;17(1):16-16
Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans
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Tooth Replantation/methods*
;
Consensus
;
Periapical Periodontitis/surgery*
8.Expert consensus on management of instrument separation in root canal therapy.
Yi FAN ; Yuan GAO ; Xiangzhu WANG ; Bing FAN ; Zhi CHEN ; Qing YU ; Ming XUE ; Xiaoyan WANG ; Zhengwei HUANG ; Deqin YANG ; Zhengmei LIN ; Yihuai PAN ; Jin ZHAO ; Jinhua YU ; Zhuo CHEN ; Sijing XIE ; He YUAN ; Kehua QUE ; Shuang PAN ; Xiaojing HUANG ; Jun LUO ; Xiuping MENG ; Jin ZHANG ; Yi DU ; Lei ZHANG ; Hong LI ; Wenxia CHEN ; Jiayuan WU ; Xin XU ; Jing ZOU ; Jiyao LI ; Dingming HUANG ; Lei CHENG ; Tiemei WANG ; Benxiang HOU ; Xuedong ZHOU
International Journal of Oral Science 2025;17(1):46-46
Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans
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Root Canal Therapy/adverse effects*
;
Consensus
;
Root Canal Preparation/adverse effects*
9.The role of DNA methylation detection in the early diagnosis and prognosis of lung cancer
Xinwen ZHANG ; Shixuan PENG ; Qing YANG ; Jiating ZHOU ; Xuan ZHANG ; Zilan XIE ; Mengle LONG ; Qingyang WEN ; Yi HE ; Zhi LI ; Yongjun WU
Chinese Journal of Laboratory Medicine 2024;47(4):371-378
Lung cancer is the leading type of cancer death, and most patients with lung cancer are diagnosed at an advanced stage and have a very poor prognosis. Although low-dose computed tomography (LDCT) has entered the clinic as a screening tool for lung cancer, its false-positive rate is more than 90%. As one of the epigenetic modifications of research hotspots, DNA methylation plays a key role in a variety of diseases, including cancer.Hypermethylation of tumor suppressor genes and hypomethylation of proto-oncogenes are important events in tumorigenesis and development. Therefore, DNA methylation analysis can provide some useful information for the early screening, diagnosis, treatment and prognosis of lung cancer. Although invasive methods such as tissue biopsy remain the gold standard for tumor diagnosis and monitoring, they also have limitations such as inconvenience in sampling. In recent years, there has been a rapid development of liquid biopsy, which can detect primary or metastatic malignancies and reflect the heterogeneity of tumors. In addition, the blood sample can be collected in a minimally invasive or non-invasive format and is well tolerated in older and frail patients. This article explores some of the emerging technologies for DNA methylation analysis and provides an overview of the application of DNA methylation in the diagnosis and treatment of lung cancer.
10.Expert consensus on difficulty assessment of endodontic therapy
Huang DINGMING ; Wang XIAOYAN ; Liang JINGPING ; Ling JUNQI ; Bian ZHUAN ; Yu QING ; Hou BENXIANG ; Chen XINMEI ; Li JIYAO ; Ye LING ; Cheng LEI ; Xu XIN ; Hu TAO ; Wu HONGKUN ; Guo BIN ; Su QIN ; Chen ZHI ; Qiu LIHONG ; Chen WENXIA ; Wei XI ; Huang ZHENGWEI ; Yu JINHUA ; Lin ZHENGMEI ; Zhang QI ; Yang DEQIN ; Zhao JIN ; Pan SHUANG ; Yang JIAN ; Wu JIAYUAN ; Pan YIHUAI ; Xie XIAOLI ; Deng SHULI ; Huang XIAOJING ; Zhang LAN ; Yue LIN ; Zhou XUEDONG
International Journal of Oral Science 2024;16(1):15-25
Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

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