Cleft lip and palate (CLP) are common congenital craniofacial developmental disorders with a high incidence rate among newborns. Due to the influence of the cleft, an increased frequency of anomalies occurs in cleft-adjacent teeth. This review summarizes the abnormality of tooth development and malposition characteristics of the central incisors, lateral incisors, and canines adjacent to the alveolar cleft in CLP patients and treatment progress in order to provide information for related clinical treatment and research. The literature reveals that central incisors, lateral incisors, and canines adjacent to the alveolar cleft exhibit various types and degrees of abnormalities. The alveolar cleft-adjacent central incisors show significantly smaller mesiodistal diameters, root lengths, and root volumes compared to the non-alveolar cleft side, while the crown-to-root ratio is larger. Further, they are inclined distally and lingually compared to the non-alveolar cleft side. The alveolar cleft-adjacent lateral incisor is the most common missing or impacted tooth and is often affected by microdontia. The total length and root length of the alveolar cleft-adjacent canines are significantly smaller, while the crown-to-root ratio is larger on the alveolar cleft side. In addition, they are inclined mesially and buccally compared to the non-alveolar cleft side. Further, they are higher positioned and located closer to the midline. For developmental anomalies, impacted central incisors can be addressed by orthodontic space preparation to facilitate eruption or surgical crown exposure and orthodontic traction. Treatment of missing lateral incisors can involve orthodontic closure of the gap or preservation of the space for subsequent prosthetic restoration. When lateral incisors present with developmental defects, such as microdontia, peg-shaped teeth, or invaginated teeth, a comprehensive decision is necessary to determine whether to retain and restore or extract the malformed lateral incisors. Treatment of impacted canines after bone grafting involves either extraction or traction to facilitate the eruption of the impacted tooth. For malposition, presurgical orthodontic treatment can correct teeth with excessive inclination or rotation on the cleft side to improve the effectiveness of bone grafting surgery. Postsurgical orthodontic treatment can enhance the stability of bone grafting surgery. Although numerous studies have explored the dental characteristics of patients with CLP, the lack of applicability and specificity still need to be elucidated, thus indicating the need for further research.

OBJECTIVE: To observe the effect of Huayu Tongluo moxibustion on the NOD-like receptor protein 3 (NLRP3)/cysteine-aspartic acid protease-1 (Caspase-1)/gasdermin D (GSDMD) signaling pathway in rats with vascular dementia (VD), and to explore its mechanism in improving learning and memory ability and alleviating neuronal injury in the hippocampal CA1 region. METHODS: A total of 80 SPF-grade male Wistar rats were included. Three rats were excluded based on the Morris water maze test. From the remaining rats, 12 were randomly selected as the sham operation group. The rest were used to establish VD models via modified bilateral common carotid artery ligation. Thirty-six successfully modeled rats were randomly divided into a model group, a medication group, and a moxibustion group, with 12 rats in each group. The medication group was treated with nimodipine solution (12 mg/kg) via gavage. The moxibustion group was treated with Huayu Tongluo moxibustion. The suspended moxibustion was applied at Shenting (GV24) and Dazhui (GV14), and aconite cake-separated moxibustion was applied at Baihui (GV20), with each acupoint treated for 20 min. All treatments were administered once daily for 21 consecutive days. Before and after modeling, and after intervention, the Morris water maze test was used to assess cognitive function. After intervention, the activation and morphology of microglia in the hippocampal CA1 region were observed by immunofluorescence. Ultrastructure of hippocampal CA1 neurons was examined by transmission electron microscopy. Western blot was used to detect protein expression of NLRP3, apoptosis-associated speck-like protein (ASC), Caspase-1, GSDMD, and interleukin-1β (IL-1β) in the hippocampal CA1 region. ELISA was used to detect the content of IL-6, IL-8, and tumor necrosis factor-α (TNF-α) in the hippocampal CA1 region. RESULTS: Compared with the sham operation group, the model group showed longer mean escape latency (P<0.01) and fewer platform crossings (P<0.01); the microglial processes in the hippocampal CA1 region were thickened, cytoplasm was hypertrophic, and relative fluorescence intensity of ionized calcium-binding adapter molecule 1 (IBA-1) was increased (P<0.05); the neuronal ultrastructure in the CA1 region was severely damaged, rough endoplasmic reticulum was swollen, mitochondria were deformed and swollen, some cristae were ruptured or dissolved, showing vacuolar changes; the protein expression of NLRP3, ASC, Caspase-1, GSDMD, and IL-1β, as well as levels of IL-6, IL-8, and TNF-α were significantly elevated (P<0.001). Compared with the model group, both the medication group and the moxibustion group showed shortened mean escape latency (P<0.01) and increased platform crossings (P<0.01); the microglial processes were thinner, and IBA-1 fluorescence intensity was decreased (P<0.05); the neuronal ultrastructure in the CA1 region was partially improved; the protein expression of NLRP3, ASC, Caspase-1, GSDMD, and IL-1β, and levels of IL-6, IL-8, and TNF-α were significantly reduced (P<0.001). Compared with the medication group, the moxibustion group showed shortened mean escape latency (P<0.05) and more platform crossings (P<0.05); the IBA-1 fluorescence intensity was decreased (P<0.05); the neuronal ultrastructure in the CA1 region was improved; the protein expression of NLRP3, ASC, Caspase-1, GSDMD, and IL-1β, as well as levels of IL-6, IL-8, and TNF-α, were significantly lower (P<0.001). CONCLUSION The Huayu Tongluo moxibustion could enhance learning and memory abilities in VD rats, inhibit excessive activation of microglia, and alleviate neuronal injury in the hippocampal CA1 region. Its mechanism may involve modulation of the NLRP3/Caspase-1/GSDMD signaling pathway, reduction of inflammatory responses.
Animals ; Male ; Dementia, Vascular/physiopathology* ; Rats ; Signal Transduction ; Moxibustion ; Rats, Wistar ; CA1 Region, Hippocampal/injuries* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Caspase 1/genetics* ; Memory ; Humans ; Neurons/metabolism* ; Learning

BACKGROUND: The profile and clinical significance of the oral microbiome in patients with non-obstructive hypertrophic cardiomyopathy (noHCM) and obstructive hypertrophic cardiomyopathy (oHCM) remain unexplored. The objective of this study was to evaluate the difference of oral microbiome between noHCM and oHCM patients. METHODS: This cross-sectional study enrolled 18 noHCM patients and 26 oHCM patients from Fuwai Hospital, Chinese Academy of Medical Sciences between 2020 and 2021. Clinical and periodontal evaluations were conducted, and subgingival plaque samples were collected. Metagenomic sequencing and subsequent microbial composition and functional analyses were performed. RESULTS: Compared to oHCM patients, those with noHCM had higher systolic blood pressure (138.1 ± 18.8 mmHg vs . 124.2 ± 13.8 mmHg, P = 0.007), a larger body circumference (neck circumference: 39.2 ± 4.0 cm vs . 35.1 ± 3.7 cm, P = 0.001; waist circumference: 99.7 ± 10.5 cm vs . 92.2 ± 10.8 cm, P = 0.027; hip circumference: 102.5 ± 5.6 cm vs . 97.5 ± 9.1 cm, P = 0.030), a greater left ventricular end-diastolic diameter (46.6 ± 4.9 mm vs . 43.1 ± 4.9 mm, P = 0.026), and a lower left ventricular ejection fraction (64.1 ± 5.7 % vs . 68.5 ± 7.8%, P = 0.048). While overall biodiversity and general microbial composition were similar between the noHCM and oHCM groups, ten taxa displayed significant differences at the genus and species levels, with Porphyromonas gingivalis showing the highest abundance and greater enrichment in noHCM (relative abundance: 7.79535 vs . 4.87697, P = 0.043). Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis identified ten distinct pathways, with pathways related to energy and amino acid metabolism being enriched in oHCM patients, and those associated with genetic information processing less abundant in the oHCM group. Metabolic potential analysis revealed ten significantly altered metabolites primarily associated with amino sugar and nucleotide sugar metabolism, porphyrin metabolism, pentose and glucuronate interconversion, and lysine degradation. CONCLUSIONS The higher abundance of Porphyromonas gingivalis , which is known to impact cardiovascular health, in noHCM patients may partially account for clinical differences between the groups. Pathway enrichment and metabolic potential analyses suggest microbial functional shifts between noHCM and oHCM patients, potentially reflecting inherent metabolic changes in HCM.
Humans ; Cardiomyopathy, Hypertrophic/microbiology* ; Female ; Male ; Microbiota/genetics* ; Middle Aged ; Cross-Sectional Studies ; Adult ; Mouth/microbiology* ; Aged

Numerous c-mesenchymal-epithelial transition (c-MET) inhibitors have been reported as potential anticancer agents. However, most fail to enter clinical trials owing to poor efficacy or drug resistance. To date, the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed. In this study, we constructed the largest c-MET dataset, which included 2,278 molecules with different structures, by inhibiting the half maximal inhibitory concentration (IC₅₀) of kinase activity. No significant differences in drug-like properties were observed between active molecules (1,228) and inactive molecules (1,050), including chemical space coverage, physicochemical properties, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles. The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding (t-SNE) high-dimensional data. Further clustering and chemical space networks (CSNs) analyses revealed commonly used scaffolds for c-MET inhibitors, such as M5, M7, and M8. Activity cliffs and structural alerts were used to reveal "dead ends" and "safe bets" for c-MET, as well as dominant structural fragments consisting of pyridazinones, triazoles, and pyrazines. Finally, the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules, including at least three aromatic heterocycles, five aromatic nitrogen atoms, and eight nitrogen-oxygen atoms. Overall, our analyses revealed potential structure-activity relationship (SAR) patterns for c-MET inhibitors, which can inform the screening of new compounds and guide future optimization efforts.

Objective:To explore the aperiodic components(1/f slopes)and their associations with cognitive impairment in patients with schizophrenia.Methods:Nineteen patients with schizophrenia according to the Interna-tional Statistical Classification of Diseases and Related Health Problem,Tenth Revision(ICD-10)and 21 normal controls were administrated the total Brief Assessment of Cognition in Schizophrenia(BACS)to measure the cogni-tive performance.The 5-minute eyes-closed and eyes-open resting EEG signals were collected and parameterized in-to aperiodic components(1/f slope).Finally,Pearson correlation was used to examine the relationships between the 1/f slope and cognition assessment scores.Results:The patients with schizophrenia had higher 1/f slope compared to HC on central location of scalp(P＜0.05).The vocal memory scores showed a significantly positive relation with 1/f slopes in patients with schizophrenia(anterior location:r=-0.68,P＜0.05;central location:r=-0.44,P＜0.05),but a significantly negative relation in normal controls(anterior location:r=0.57,P＜0.05;posterior lo-cation:r=0.54,P＜0.05).Conclusion:The 1/f slopes of EEG in schizophrenia were steeper than normal control,suggesting its strong cognitive functional significance and complex mechanisms in schizophrenia.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.

Objective:To evaluate the efficacy and safety of baricitinib combined with ruxolitinib cream in the treatment of progressive nonsegmental vitiligo.Methods:Clinical data were retrospectively collected from patients with progressive nonsegmental vitiligo in Boao Super Hospital. All the patients were treated with oral baricitinib daily (2 mg/day for patients weighing ≤ 50 kg; 4 mg/day for those > 50 kg) in combination with topical application of ruxolitinib cream twice daily for 24 consecutive weeks. Disease severity was assessed using the facial vitiligo area scoring index (F-VASI) and total body VASI (T-VASI) at baseline, week 12, and week 24. Adverse reactions were monitored throughout the treatment course.Results:Six patients with progressive nonsegmental vitiligo were collected, including 3 males and 3 females, aged 26 - 42 years, with the disease duration ranging from 0.5 to 25 years. At week 12, 3 patients achieved a 50% ~ < 75% improvement in facial vitiligo lesions (F-VASI 50), 1 patient achieved F-VASI 75 (75% ~ < 90% improvement), and 1 patient achieved T-VASI 50; at week 24, 4 patients achieved F-VASI 50, 1 patient achieved F-VASI 75, 1 patient achieved F-VASI 90 (≥ 90% improvement), and 3 patients achieved T-VASI 50. During the treatment, upper respiratory infection occurred in 1 patient, acne in 1 patient, pruritus in 2 patients, elevation of total cholesterol levels in 2 patients, and increase of high-density lipoprotein levels in 2 patients. No severe adverse events were observed during the treatment.Conclusion:The combination therapy with baricitinib and ruxolitinib cream may have potential efficacy and safety in the treatment of progressive nonsegmental vitiligo.

Objective To examine the clinical efficacy of Tongtiao Xinshen acupuncture combined with Wenyang Bushen moxibustion in the treatment of vascular dementia(VD),and its effects on event-related potential P300,neuron specific enolase(NSE),and acetylcholinesterase(AChE).Methods Totally 60 patients diagnosed with VD were divided into acupuncture and moxibustion group and the Western medicine group according to random number table method,with 30 patients in each group.Both groups received basic Western medicine treatments such as blood pressure regulation,blood glucose regulation,and blood lipid regulation;Western medicine group was given donepezil hydrochloride tablets,5 mg each time,once a day,orally;in the acupuncture and moxibustion group,on the basis of the treatment of the Western medicine group,Tongtiao Xinshen acupuncture was combined with Wenyang Bushen moxibustion,once a day,6 times a week;the treatment for both groups lasted for 4 weeks.The scores of Mini Mental State Examination(MMSE)and Activities of Daily Living(ADL)in two groups of patients were evaluated before and on the day after treatment.The event-related potential P300 was measured and the abnormal detection rate changes of MMSE and P300 were determined.Safety indicators of both groups were monitored.Results Compared with before treatment,the scores of MMSE and ADL in the two groups significantly increased(P＜0.05),the latency of P300 in the acupuncture and moxibustion group decreased and the amplitude of P300 increased(P＜0.05),and NSE and AChE levels decreased(P＜0.05).Compared with the Western medicine group,after treatment,MMSE score,ADL score and the amplitude of P300 in the acupuncture and moxibustion group increased,the latency of P300 decreased,and the levels of NSE and AChE decreased(P＜0.05).The detection rate of P300 latency abnormalities in patients was significantly higher than that of MMSE abnormalities(P＜0.05);compared with before treatment,the abnormal rate of P300 latency and MMSE score of patients in the acupuncture and moxibustion group decreased(P＜0.05).No significant adverse reactions were observed in both groups.Conclusion Tongtiao Xinshen acupuncture combined with Wenyang Bushen moxibustion can enhance cognitive function and everyday life abilities.The mechanism may be related to the reduction of NSE and AChE levels,and event-related potential P300 is more sensitive than MMSE in determining VD and cognitive ability.

Numerous c-mesenchymal-epithelial transition(c-MET)inhibitors have been reported as potential anticancer agents.However,most fail to enter clinical trials owing to poor efficacy or drug resistance.To date,the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed.In this study,we constructed the largest c-MET dataset,which included 2,278 molecules with different struc-tures,by inhibiting the half maximal inhibitory concentration(IC50)of kinase activity.No significant differences in drug-like properties were observed between active molecules(1,228)and inactive mol-ecules(1,050),including chemical space coverage,physicochemical properties,and absorption,distri-bution,metabolism,excretion,and toxicity(ADMET)profiles.The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding(t-SNE)high-dimensional data.Further clustering and chemical space networks(CSNs)analyses revealed commonly used scaffolds for c-MET inhibitors,such as M5,M7,and M8.Activity cliffs and structural alerts were used to reveal"dead ends"and"safe bets"for c-MET,as well as dominant structural fragments consisting of pyr-idazinones,triazoles,and pyrazines.Finally,the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules,including at least three aromatic het-erocycles,five aromatic nitrogen atoms,and eight nitrogen-oxygen atoms.Overall,our analyses revealed potential structure-activity relationship(SAR)patterns for c-MET inhibitors,which can inform the screening of new compounds and guide future optimization efforts.