Type 2 diabetes (T2D) is an independent risk factor for cognitive impairment. The dysregulation of hypoxia inducible factor (HIF) signaling in T2D patients results in impaired adaptive responses to hypoxia, thereby accelerating the progression of complications. However, limited knowledge is available regarding its precise function in diabetes-associated cognitive impairment (DACI). Here, elevated HIF-1α levels were observed in brain endothelial cells (ECs) of db/db mice. Functionally, brain ECs-specific knockdown of H if1 a significantly ameliorated T2D-induced memory loss and neuronal damage. Glycolysis in brain ECs was inhibited in this process, as indicated by RNA-seq, leading to decreased hippocampal lactate production through reduced LDHA expression. Notably, T2D patients showed increased cerebrospinal fluid lactate levels, which were strongly associated with their cognitive dysfunction. Intrahippocampal injection of lactate accelerated cognitive dysfunction and impaired adult hippocampal neurogenesis (AHN) in db/db mice. Conversely, reducing hippocampal lactate levels through the intrahippocampal injection of oxamate delayed the onset of memory deficits. Furthermore, asiatic acid was discovered to protect db/db mice from cognitive impairment by decreasing brain endothelial HIF-1α expression and subsequently reducing hippocampal lactate-induced AHN damage. Overall, this study elucidates the inhibiting role played by endothelial HIF-1α-driven lactate in AHN and highlights a potential tactic of targeting HIF-1α in brain ECs for treating cognitive impairment.

Cancer stem cells (CSCs) are widely acknowledged as primary mediators to the initiation and progression of tumors. The association between microbial infection and cancer stemness has garnered considerable scholarly interest in recent years. Porphyromonas gingivalis (P. gingivalis) is increasingly considered to be closely related to the development of oral squamous cell carcinoma (OSCC). Nevertheless, the role of P. gingivalis in the stemness of OSCC cells remains uncertain. Herein, we showed that P. gingivalis was positively correlated with CSC markers expression in human OSCC specimens, promoted the stemness and tumorigenicity of OSCC cells, and enhanced tumor formation in nude mice. Mechanistically, P. gingivalis increased lipid synthesis in OSCC cells by upregulating the expression of stearoyl-CoA desaturase 1 (SCD1) expression, a key enzyme involved in lipid metabolism, which ultimately resulted in enhanced acquisition of stemness. Moreover, SCD1 suppression attenuated P. gingivalis-induced stemness of OSCC cells, including CSCs markers expression, sphere formation ability, chemoresistance, and tumor growth, in OSCC cells both in vitro and in vivo. Additionally, upregulation of SCD1 in P. gingivalis-infected OSCC cells was associated with the expression of KLF5, and that was modulated by P. gingivalis-activated NOD1 signaling. Taken together, these findings highlight the importance of SCD1-dependent lipid synthesis in P. gingivalis-induced stemness acquisition in OSCC cells, suggest that the NOD1/KLF5 axis may play a key role in regulating SCD1 expression and provide a molecular basis for targeting SCD1 as a new option for attenuating OSCC cells stemness.
Porphyromonas gingivalis/pathogenicity* ; Stearoyl-CoA Desaturase/metabolism* ; Humans ; Carcinoma, Squamous Cell/pathology* ; Mouth Neoplasms/metabolism* ; Animals ; Neoplastic Stem Cells/microbiology* ; Mice, Nude ; Mice ; Nod1 Signaling Adaptor Protein/metabolism* ; Kruppel-Like Transcription Factors/metabolism* ; Cell Line, Tumor

Patients with periodontal disease often require combined periodontal-orthodontic interventions to restore periodontal health, function, and aesthetics, ensuring both patient satisfaction and long-term stability. Managing these patients involving orthodontic tooth movement can be particularly challenging due to compromised periodontal soft and hard tissues, especially in severe cases. Therefore, close collaboration between orthodontists and periodontists for comprehensive diagnosis and sequential treatment, along with diligent patient compliance throughout the entire process, is crucial for achieving favorable treatment outcomes. Moreover, long-term orthodontic retention and periodontal follow-up are essential to sustain treatment success. This expert consensus, informed by the latest clinical research and practical experience, addresses clinical considerations for orthodontic treatment of periodontal patients, delineating indications, objectives, procedures, and principles with the aim of providing clear and practical guidance for clinical practitioners.
Humans ; Consensus ; Orthodontics, Corrective/standards* ; Periodontal Diseases/complications* ; Tooth Movement Techniques/methods* ; Practice Guidelines as Topic

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

In order to investigate the chemical constituents of glycosides in Piper sintenense Hatusima, column chromatographic techniques such as silica gel, ODS, MCI GEL CHP20P, Sephadex LH-20, and semi-preparative high performance liquid chromatography were used to afford nine glycosides from the n-butanol part of the 95% ethanol extract of Piper sintenense Hatusima. Based on the physicochemical properties and NMR data, the above compounds were identified as (2S)-2-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-1-propanone-2-O-β-D-glucopyranoside (1), 2-phenylethyl β-D-glucopyranoside (2), benzyl α-L-arabinopyranosyl-(1''→6')-β-D-glucopyranoside (3), benzyl β-D-xylopyanosyl-(1''→6')-β-D-glucopyranoside (4), phenethyl β-D-apiofuranosyl-(1''→ 2')-β-D-glucopyranoside(5), salidroside (6), phenethanol β-D-xylopyanosyl-(1''→6')-β-D-glucopyranoside (7), (Z)-hexenyl-O-α-L-arabinopyranosyl-(1''→6')-O-β-D-glucopyranoside (8), (Z)-hexenyl-O-β-D-xylopyanosyl-(1''→6')-O-β-D-glucopyranoside (9). Compound 1 was identified as a new compound, and compounds 3-9 were isolated from the genus Piper for the first time.

Objective To explore the experience and causes of self-neglect of elderly diabetic patients in community,so as to provide references for community nursing workers to identify and intervene the self-neglect behavior of elderly diabetic patients.Methods An interpretative phenomenological method was used to collect data from elderly diabetic patients registered in 3 community health service centers in Hangzhou,Zhejiang Province through semi-structured interviews.Van Manen's method was used to analyze qualitative data.Results The experience and reasons of self-neglect of elderly diabetic patients in community were summarized into 4 themes and 10 sub-themes,including neglecting personal health(low sense of self-worth,high level of self-esteem,being afraid of compromising the family),neglecting blood glucose management(weak health awareness,difficulty in blood glucose management),inadequate self-care capacity(poor financial situation,insufficient personal time,diminished mobility)and inadequate perceived support(low social support,insufficient emotional support).Conclusion The experience and reasons of self-neglect of elderly diabetic patients in community are diversified.Community health services and nursing workers should pay attention to the performance of self-neglect behavior of elderly diabetic patients and actively explore effective prevention and intervention measures.

Odontogenic maxillary sinusitis(OMS)is a subtype of maxillary sinusitis(MS).It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion.Due to the lack of unique clinical features,OMS is difficult to distinguish from other types of rhinosinusitis.Besides,the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis.Its current diagnosis and treatment are thus facing great difficulties.The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS.However,this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality.Based on systematically reviewed literature and practical experiences of expert members,our consensus focuses on characteristics,symptoms,classification and diagnosis of OMS,and further put forward multi-disciplinary treatment decisions for OMS,as well as the common treatment complications and relative managements.This consensus aims to increase attention to OMS,and optimize the clinical diagnosis and decision-making of OMS,which finally provides evidence-based options for OMS clinical management.

Endo-periodontal lesions(EPLs)involve both the periodontium and pulp tissue and have complicated etiologies and pathogenic mechanisms,including unique anatomical and microbiological characteristics and multiple contributing factors.This etiological complexity leads to difficulties in determining patient prognosis,posing great challenges in clinical practice.Furthermore,EPL-affected teeth require multidisciplinary therapy,including periodontal therapy,endodontic therapy and others,but there is still much debate about the appropriate timing of periodontal therapy and root canal therapy.By compiling the most recent findings on the etiology,pathogenesis,clinical characteristics,diagnosis,therapy,and prognosis of EPL-affected teeth,this consensus sought to support clinicians in making the best possible treatment decisions based on both biological and clinical evidence.

Objective:To evaluate the clinical outcomes after implant restoration in the posterior region of severe periodontitis patients and to investigate the factors of natural tooth affecting the implant from the perspective of improving natural periodontal health, which may provide a reference for clinical practice.Methods:Fifty-three patients with severe periodontitis who visited the Department of Periodontology at the Affiliated Stomatological Hospital of China Medical University from June 2014 to June 2023 and completed posterior implant treatment with single crown were included, among which were 16 males and 37 females, aged (52.2±8.0) years old, with a total of 136 implants, 135 adjacent natural teeth in the edentulous area. We retrospectively compared the changes of probing depth (PD), bleeding on probing (BOP) and tooth mobility (TM) before and after implant placement. Besides, we explored the effects of the natural periodontal status on PD, BOP and marginal bone loss (MBL) of the implant at the last follow-up examination by univariate analysis and multivariate analysis.Results:Fifty-three patients were followed up for (44.5±14.1) months in average, with longest interval of (8.3±2.7) months. The PD of adjacent natural teeth in the edentulous area improved from 4.3 (3.6, 4.6) mm before implantation to 3.6 (3.2, 4.0) mm in the last review ( P<0.01), while the proportion of BOP (+) improved from 69.6% (94/135) before implantation to 46.7% (63/135) in the last review ( P<0.01). The proportion of teeth with mobility≥Ⅱ decreased from 15.6% (21/135) to 5.9% (8/135) ( P<0.01). The percentage of natural teeth with PD≥4 mm in the same segment improved from 21.0% (13.3%, 26.0%) before implantation to 18.0% (12.0%, 25.0%) in the last review ( P<0.05). The BOP (+)% improved from 29.0% (24.0%, 35.0%) before implantation to 23.0% (18.0%, 31.0%) in the last review ( P<0.05), and the number of teeth with mobility≥Ⅱ decreased from 0.0 (0.0, 1.0) to 0.0 (0.0, 0.8) ( P<0.05). The functional tooth unit score of full natural teeth increased from 8.0 (6.0, 10.0) points before implantation to 12.0 (12.0, 12.0) points in the last review ( P<0.01). PD≥4 mm % increased from 11.0% (6.0%, 25.0%) before implantation to 13.0% (3.0%, 21.0%) in the last review ( P<0.05) and there was no significant differences in BOP (+)% [(17.0±9.7) % vs (14.6±7.2) %, P>0.05]. The number of teeth with mobility≥Ⅱ decreased from 1.0 (0.0, 1.8) to 0.0 (0.0, 0.8) ( P<0.05). Conclusions:Under the premise of regular supportive care, implant restorative treatment in the posterior region of severe periodontitis patients is helpful to improve the PD, BOP and TM of remaining natural teeth. Besides, the stages and grades of periodontitis at initial diagnosis can affect the PD and BOP of implants.

Aim To investigate the inhibition role and mechanism of adipose derived mesenchymal stem cell(ADMSC)exosomes(Exo)on adverse ventricular remodeling after myocardial infarction(MI).Methods The chan-ges of autophagy and inflammasomes phenotype of cardiac fibroblasts after H2O2 treatment were observed.MI rats were in-jected with an equal volume of normal saline,adipose derived mesenchymal stem cell exosomes(MSC-Exo)or fibroblast exosomes(MEF-Exo)via a tail vein.The expression of autophagy related 16 like protein 1(ATG16L1),autophagy re-lated protein 7(ATG7)and NOD-like receptor protein 3(NLRP3),inflammatory response,the degree of myocardial fi-brosis,and the cardiac function were observed in different groups.Results After treatment with H2O2 on cardiac fi-broblasts,the expressions of ATG16L1 and ATG7 were significantly decreased(P＜0.001),NLRP3 was significantly in-creased(P＜0.001),and the levels of inflammatory cytokines interleukin-1β(IL-1β)and IL-18 were significantly elevated(P＜0.001).After MI rats were intervened with MSC-Exo,the expressions of autophagy related proteins ATG16L1 and ATG7 were significantly up-regulated(P＜0.001),NLRP3 was significantly down-regulated(P＜0.001),serum IL-1β and IL-18 levels were significantly decreased(P＜0.001),fibrosis-related proteins collagen Ⅰ and Ⅲ were significantly reduced(P＜0.001),myocardial fibrosis was significantly relieved(P＜0.001),and cardiac function was sig-nificantly improved(P＜0.001).Conclusion Adipose derived MSC-Exo play a role in inhibiting adverse ventricular remodeling after MI by regulating the balance of autophagy and NLRP3 inflammasomes.