This case report presents a 16-year-old male patient with deficiency of adenosine deaminase 2(DADA2). The patient had a history of Raynaud′s phenomenon with digital ulcers since childhood. As the disease progressed, the patient developed retinal vasculitis, intracranial hemorrhage, skin necrosis, severe malnutrition, refractory hypertension, and gastrointestinal bleeding. Genetic testing revealed compound heterozygous mutations in the ADA2 gene (paternal c.1072G > A pathogenic mutation + maternal c.1065C > A variant of unknown clinical significance). ADA2 enzyme activity was significantly reduced (0.1 U/L). A multidisciplinary treatment team developed an individualized plan to address key issues, including nutritional support, blood pressure control, rehabilitation, pain management, and balancing anticoagulation/bleeding risks. After systematic intervention, the patient′s condition showed partial improvement. This case reveals clinical challenges such as anticoagulation decisions and nutritional support of DADA2. It also emphasizes the importance of early molecular diagnosis, tumor necrosis factor-α inhibitor targeted therapy, and multidisciplinary collaboration in management, underlining the core value of precision medicine in rare disease management.

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* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

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 ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

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 ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

Objective To investigate the clinical characteristics and prognostic factors of the limited-stage disease (LD) and extensive-stage disease (ED) of primary esophageal small cell carcinoma (PESCC). Methods The clinical data and follow-up information of 72 patients with PESCC were retrospectively analyzed. Chi-square test was used to compare the baseline data of patients with LD and ED, Kaplan-Meier method was employed to draw the survival curve of both groups, and Log-rank test was employed to compare survival rates between groups. Univariate and multivariate Cox regression methods were used to analyze the factors affecting the overall survival (OS) of patients with LD and ED. Results A total of 49 patients with LD and 23 patients with ED were included in this study. The median survival time of patients with LD was 18.300 months and that of patients with ED was 10.903 months (P=0.029). Total protein (TP) value (HR=0.890, 95%CI: 0.805−0.983, P=0.022) and chemotherapy cycle number (HR=0.388, 95%CI: 0.187−0.807, P=0.011) were independent prognostic factors of patients with LD. Systemic immune-inflammation index (SII) (HR=1.002, 95%CI: 1.000−1.004, P=0.007) and C-reactive protein (CRP) (HR=1.065, 95%CI: 1.021−1.111, P=0.004) were independent prognostic factors of patients with ED. Conclusion The malignant degree of PESCC is high, and prognosis is poor. Patients with LD and ED have different prognostic factors. Total protein value and chemotherapy cycle are independent prognostic factors of patients with LD. SII and CRP are independent prognostic factors of patients with ED.

BACKGROUND:Existing studies have confirmed that exosomes can effectively promote pulp regeneration.However,the biological functions and properties of exosomes from preconditioned sources can be significantly changed,which have different effects on cell proliferation,migration and odontogenic differentiation. OBJECTIVE:To discuss the application status of exosomes and their preconditioning methods in the field of pulp regeneration,and summarize the preconditioning methods that affect the function of exosomes,and explore the effect of exosomes and their preconditioning on pulp regeneration. METHODS:The relevant articles were searched in WanFang,CNKI,PubMed,and Web of Science databases from 2006 to 2022.The Chinese and English search terms were"exosomes,pulp regeneration;preconditioning method".A total of 78 articles were included for analysis. RESULTS AND CONCLUSION:(1)Exosomes have the advantages of good biocompatibility,low immunogenicity and no cytotoxicity,and can induce the regeneration of pulp tissue by promoting stem cell tooth formation,neurogenesis and vascularization.(2)Exosomes derived from preconditioning can enhance the ability of tissue repair and regeneration and have a significant impact on the quality of regenerated dental pulp.(3)Currently,the preconditioning methods used in the field of dental pulp regeneration include inflammatory stimulation,hypoxia induction,conditioned medium and three-dimensional culture,and secreted exosomes can effectively improve the quality of regenerated dental pulp.Nevertheless,the specific effect and mechanism of different preconditioning methods on pulp regeneration need to be explored.

BACKGROUND:Fluorosis is a disorder of enamel development caused by long-term intake of large amounts of fluoride during enamel development. OBJECTIVE:To further explore the molecular mechanism of dental fluorosis formation by screening the differentially expressed genes associated with calcium homeostasis in ameloblasts by transcriptome sequencing technology. METHODS:LS8 cells were treated with 0,0.4,0.8,1.6,3.2 and 6.4 mmol/L sodium fluoride(NaF)for 24,48 and 72 hours to observe the effects of different concentrations of NaF on the morphology,cell activity and intracellular Ca2+ concentration of LS8 cells.The differentially expressed genes were screened by transcriptome sequencing and validated. RESULTS AND CONCLUSION:After 24 hours of treatment,the cells treated with 0,0.4,and 0.8 mmol/L NaF were in good growth condition,with increased cell number and clear cell outline.When the NaF concentration was≥1.6 mmol/L,the cells were gradually shrunken and became smaller and the number of cells decreased with the increase of NaF concentration.After 48 and 72 hours of treatment,the number of cells increased in the 0,0.4 mmol/L NaF groups,while gradually decreased in the 0.8,1.6,3.2 mmol/L NaF groups,with rounded and smaller cell morphology.The cells in the 6.4 mmol/L NaF group were shrunken,rounded and suspended in the medium,with almost no adherent cells.When treated with the same concentration of NaF,LS8 cells were in optimal growth after 24 hours of treatment.Results from cell counting kit-8 assay showed that when treated with the same concentration of NaF,the cell activity decreased with the increase of treatment time;when the treatment time was the same,the cell activity decreased with the increase of NaF concentration.After 24 hours of treatment,the intracellular Ca2+ concentration increased with the increase of NaF concentration.Transcriptome sequencing analysis identified genes involved in the regulation of cellular calcium homeostasis:Hsp90b1,Canx,Calr,and Hspa5 that were significantly upregulated(P＜0.05)and Cacna1a that was significantly downregulated(P＜0.05).To conclude,the inhibitory effect of NaF on LS8 cell proliferation may be related to the abnormal increase in intracellular Ca2+ concentration,and the mechanism may be caused by the upregulation of the expression of protein processing and synthesis pathways Hsp90b1,Canx,Calr,and Hspa5 and the downregulation of the expression of calcium signaling pathway Cacna1a.

Cognitive impairment is a common clinical complication in type 2 diabetes (T2DM). T2DM-related cognitive impairment has complex and multifactorial pathogenesis. Cerebral microvascular dysfunction is an important pathological change in patients with T2DM and pre-T2DM, and it can induce blood-brain barrier injury and impaired blood perfusion regulation, with disturbed neurovascular coupling and cerebral autoregulation, leading cognitive impairment. This article reviews the epidemiology and pathophysiological mechanisms related to T2DM cerebral microvascular lesions and cognitive impairment, and how to monitor changes of cerebral microvascular structure and function so as to provide new approach for diagnosis and treatment of T2DM-related cognitive impairment.

ObjectiveTo provide technical support for the molecular surveillance of pathogenic bacteria strains carrying mobile colistin resistance-1 （mcr⁃1） gene isolate from inlet of wastewater treatment plants （WWTP）. MethodsThe Enterobacteriaceae strains carrying mcr⁃1 resistance gene isolate from inlet of WWTP during April 1 to June 30， 2023 in Shanghai were cultured on blood-rich and SS culture medium and were identified using a mass spectrometry analyzer. The mcr⁃1 gene and copy number were detected by real-time fluorescence quantitative PCR. Drug susceptibility test was performed by microbroth dilution method. The copy numbers of Escherichia coli carrying mcr⁃1 gene isolated from wastewater and human fecel were statistically analyzed by SPSS 25.0. ResultsA total of 14 strains carrying the mcr⁃1 gene were isolated from 49 WWTP samples， and the positive isolation rate was 28.6%， including 12 non-diarrheal E. coli strains and 2 Klebsiella pneumoniae strains. The drug susceptibility results showed that all 14 strains were multi-drug resistant bacteria. They were all sensitive to imipenem and tigecycline， but were ampicillin- and cefazolin-resistant. There was no significant difference in the copy number between human-sourced diarrheal E. coli and wastewater-sourced non-diarrheal E. coli （t=0.647， P>0.05）. ConclusionThe isolation and identification of strains carrying the mcr⁃1 gene from inlet of WWTP samples were firstly established in Shanghai. The multi-drug resistance among the isolated strains is severe. To effectively prevent and control the spread of colistin-resistant bacteria， more attention should be paid to the surveillance of mcr⁃1 gene.

Objective:To understand the infection status, epidemiological characteristics and drug resistance of Diarrheagenic Escherichia coli (DEC) in Shanghai and provide evidence for the disease surveillance. Methods:The epidemiological data of diarrhea cases in Shanghai from 2016 to 2022 were collected from Shanghai Diarrhea Comprehensive Surveillance System, and stool samples were collected from the cases for DEC detection. The drug resistance data was obtained from Chinese Pathogen Identification Network. Statistical analysis was conducted by using χ2 and fisher test. Results:In 24 883 diarrhea cases detected during 2016-2022, the DEC positive rate was 9.13% (2 271/24 883), the single DEC positive rate was 8.83% (2 197/24 883) and the mixed DEC positive rate was 0.30% (74/24 883). The main type of DEC was Enterotoxigenic Escherichia coli (ETEC) [4.33% (1 077/24 883)]. The DEC positive rate was highest in people aged ≤5 years 18.48% (22/119). The annual peak of DEC positive rate was observed during July - September [5.91% (1 470/24 883)]. The DEC positive rate were 9.47% (554/5 847) and 9.02% (1 717/19 036) in urban area and in suburbs, respectively, Enteroaggregative Escherichia coli (EAEC) [3.98% (233/5 847)] and ETEC [4.56% (868/19 036)] were mainly detected. From 2016 to 2019, the DEC positive rate was 9.42% (1 821/19 330), while it was 8.10% (450/5 553) from 2020 to 2022, the main DEC types were ETEC (4.87%, 941/19 330) and EAEC (4.70%, 261/5 553). The multi-drug resistance rate was 40.21% (618/1 537). The top three antibiotics with high drug resistance rates were ampicillin [64.74% (995/1 537)], nalidixic acid [58.49% (899/1 537)] and tetracycline [45.09% (693/1 537)]. Conclusions:Compared with 2016- 2019, a decrease in DEC detection rate was observed during 2020-2022, and the main type of DEC detected shifted from ETEC to EAEC. The prevalence of multi-drug resistance was severe. Therefore, it is necessary to further strengthen the surveillance for DEC drug resistance and standardize the use of clinical antibiotics.