Age-related macular degeneration (AMD) seriously endangers the visual health of the elderly, and its incidence rate is on the rise in recent years.As the aging of the population intensifies, the incidence rate of AMD will continue to rise.Therefore, it is crucial to explore its genetic pathogenic mechanism.Genome-wide association studies (GWAS) have identified a large number of single nucleotide polymorphisms associated with AMD.However, most of these polymorphisms are located in noncoding regions, and their functions are unclear.Therefore, revealing the regulatory effects of the genetic variations on gene expression, protein levels, and metabolite abundance serves as a powerful tool for deciphering the functions of noncoding variations discovered in GWAS.Furthermore, combining quantitative trait loci (QTLs) with GWAS can effectively explain GWAS data and increase the likelihood of discovering statistically significant genetic variation loci.This review summarizes research on the analysis and integration of GWAS combined with QTL data, aiming to better understand the impact of gene variations on the occurrence and development of AMD, thereby providing new ideas for searching for effective therapeutic targets for AMD.

Objective:To investigate the expression of interleukin (IL)-22 in lung adenocarcinoma and its effect and possible mechanism for lung adenocarcinoma metastasis.Methods:The cancer tissues and paired adjacent normal tissues (>2 cm from the tumor edge) surgically removed from 27 lung adenocarcinoma patients in Tianjin Medical University Cancer Institute & Hospital from January to June 2023 were retrospectively collected. Flow cytometry was used to detect the expression levels of IL-22 in T cells of all tissues, and the expression levels of IL-22 in T cells were compared between cancer and adjacent tissues, as well as between lung cancer tissues of patients with and without lymph node metastasis. The cancer tissues and paired adjacent normal tissues were retrospectively collected from 6 patients with lung adenocarcinoma during the same period, and the expression level of IL-22 receptor IL-22RA1 in the tissues was detected by Western blotting. IL-22RA1 transcriptome data from cancer tissues of lung adenocarcinoma patients in 3 datasets in The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database were collected. Using the R software survminer package to select the optimal critical value of IL-22RA1 that reflected the survival relationship, and patients were divided into high and low IL-22RA1 groups based on this. The survival package was used to draw the overall survival curve and log-rank test was performed for inter group comparison. Recombinant IL-22 was used to treat human lung adenocarcinoma A549 cells and mouse lung adenocarcinoma LLC cells, with cells not treated with IL-22 as controls; Transwell assay was used to detect the number of migrating cells in each group; Western blotting was used to detect the expression levels of ERK, AKT and STAT signaling pathways-related proteins, matrix metalloproteinase 9 (MMP-9) and epithelial cadherin (E-cad) in each group of cells. The expression levels of these proteins in A549 cells and LLC cells were also measured after the addition of STAT3 inhibitor C188-9, AKT inhibitor MK-2206 and ERK inhibitor SCH772984. A lung metastasis model of LLC cells was constructed using 10 C57BL/6 mice, the mice were randomly divided into the experimental group and the control group using simple randomization method. IL-22 neutralizing antibody (50 μg/mouse) and non-neutralizing control antibody (50 μg/mouse) were injected once every other day. On the 10th day, the mice were euthanized and dissected to count lung metastatic nodules. The metastatic lung tissue was stained with HE and the metastatic foci were counted. Flow cytometry was used to detect the proportion of CD4 + T cells and CD8 + T cells to immune cells in single cells prepared from metastatic lung tissue. Results:The flow cytometry analysis showed that the proportion of IL-22 + CD4 + T cells in T cells (labeled with CD3 and CD45) in 27 clinically collected lung adenocarcinoma tissues [ M ( Q1, Q3)] was higher than that in adjacent normal tissues [0.28% (0.04%, 1.00%) vs. 0.01% (0.00%, 0.25%)]. The proportion of IL-22 + CD4 + T cells in lung adenocarcinoma tissues of patients with metastasis (9 cases) was higher than that of patients without metastasis (18 cases) [1.06% (0.49%, 4.72%) vs. 0.15% (0.00%, 0.35%)], and the differences were statistically significant (both P < 0.01). Western blotting analysis showed that the relative expression level of IL-22RA1 protein in lung adenocarcinoma tissues was higher than that in adjacent normal tissues (1.03±0.25 vs. 0.35±0.10), and the difference was statistically significant ( P < 0.05). The overall survival of the IL-22RA1 low expression group in lung adenocarcinoma tissues was better than that of the IL-22RA1 high expression group in the TCGA database and GEO databases GSE42127, GSE29016 and GSE26939 datasets, and the differences were statistically significant (all P < 0.001). Transwell assay showed that A549 cells [(744±40) cells, (770±64) cells vs. (403±42) cells] and LLC cells [(167±39) cells, (246±80) cells vs. (31±5) cells] treated with 100 and 200 ng/ml IL-22 for 24 hours had fewer migration numbers than the control group, and the differences were statistically significant (both P < 0.01). Western blotting analysis showed that during treatment with 100 ng/ml recombinant IL-22 for 15-1 440 minutes, the levels of p-STAT3, p-ERK and p-AKT proteins in A549 and LLC cells were higher than those in the control group, while there was no difference in the levels of E-cad and MMP-9 proteins between the two groups. After the combined treatment of recombinant IL-22 and STAT3, AKT or ERK inhibitor, the corresponding levels of p-STAT3, p-AKT and p-ERK proteins in A549 and LLC cells were similar to those in cells without inhibitor and recombinant IL-22 treatment, but significantly lower than those in cells treated with recombinant IL-22 alone. In the dissected lung tissues of mice lung metastasis models, the experimental group had fewer metastatic lung nodules than the control group (2.3±0.6 vs. 7.0±2.0), and the difference was statistically significant ( t = 3.88, P = 0.018). In the morphological observation of lung metastasis tissues, the experimental group had fewer metastatic lesions than the control group (1.8±0.8 vs. 5.4±1.1), and the difference was statistically significant ( t = 5.69, P < 0.001). Flow cytometry analysis showed that the proportion of CD8 + T cells in immune cells in the lung tissues of mice in the experimental group (labeled with CD45) was higher than that in the control group [(27±5)% vs. (15±5)%], and the difference was statistically significant ( t = 3.01, P = 0.040). There was no statistically significant difference in the proportion of CD4 + T cells in immune cells between the two groups ( P > 0.05). Conclusions:The expression levels of IL-22 and its receptor IL-22RA1 in lung adenocarcinoma tissues are higher than those in adjacent normal tissues, and the high expression level of IL-22RA1 in cancer tissues may be associated with poor prognosis of patients; on the one hand, IL-22 may promote the migration of lung adenocarcinoma cells by activating the ERK, AKT and STAT3 signaling pathways, and on the other hand, it may promote lung adenocarcinoma metastasis by reducing CD8 + T cell infiltration in the immune microenvironment of lung adenocarcinoma.

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.

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.

Objective To investigate the nutritional quality characteristics of vitamin D3-fortified yogurt and explore its improving effect on vitamin D metabolism in the body under simulated weightlessness,thereby providing a theoretical basis for the development of functional foods.Methods Using reconstituted milk as the matrix and Vitamin D3(VD3)microcapsule powder as the fortifier,VD3-fortified yogurt was prepared.A systematic study was conducted to investigate the effects of different gradients(1.25 μg/100 mL,2.50 μg/100 mL,3.75 μg/100 mL,5.00 μg/100 mL,6.25 μg/100 mL)of VD3 microcapsule addition on its quality characteristics(titratable acidity,solid content,water-holding capacity,syneresis).In vivo assessments were conducted using a Sprague-Dawley(SD)rat tail-suspension model to simulate weightlessness.Levels in serum 25(OH)D3,1,25-(OH)2D3,calcium(Ca),and phosphorus(P)were detected using the enzyme-linked immunosorbent assay(ELISA)to evaluate its metabolic capacity.Results During fermentation(3 h),titratable acidity of VD?-fortified yogurt initially increased,then decreased,and eventually stabilized with rising microcapsule dosage,while total solid content remained consistent.WHC exhibited an initial increase followed by a decline,whereas syneresis showed an inverse trend.At an optimal dosage of 3.75 μg/100 mL,the yogurt displayed a dense and uniform network structure,characterized by non-Newtonian fluid behavior with shear-thinning properties.This formulation demonstrated robust structural stability under high-frequency mechanical stress,alongside desirable textural,flavor,and sensory attributes.Animal experiments revealed that the serum concentrations of 25(OH)D3,1,25-(OH)2D3,calcium,and phosphorus in the vitamin D?-fortified yogurt intervention group were significantly higher than those in the tail-suspended control group(P<0.05).Conclusion VD? microencapsulation technology effectively preserves and enhances the nutritional quality characteristics of yogurt and mitigates vitamin D metabolic dysregulation under simulated weightlessness.

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.

Protrusive facial deformities, characterized by the forward displacement of the teeth and/or jaws beyond the normal range, affect a considerable portion of the population. The manifestations and morphological mechanisms of protrusive facial deformities are complex and diverse, requiring orthodontists to possess a high level of theoretical knowledge and practical experience in the relevant orthodontic field. To further optimize the correction of protrusive facial deformities, this consensus proposes that the morphological mechanisms and diagnosis of protrusive facial deformities should be analyzed and judged from multiple dimensions and factors to accurately formulate treatment plans. It emphasizes the use of orthodontic strategies, including jaw growth modification, tooth extraction or non-extraction for anterior teeth retraction, and maxillofacial vertical control. These strategies aim to reduce anterior teeth and lip protrusion, increase chin prominence, harmonize nasolabial and chin-lip relationships, and improve the facial profile of patients with protrusive facial deformities. For severe skeletal protrusive facial deformities, orthodontic-orthognathic combined treatment may be suggested. This consensus summarizes the theoretical knowledge and clinical experience of numerous renowned oral experts nationwide, offering reference strategies for the correction of protrusive facial deformities.
Humans ; Orthodontics, Corrective/methods* ; Consensus ; Malocclusion/therapy* ; Patient Care Planning ; Cephalometry