ObjectiveThis paper aims to observe the protective effect of Huamoyan granules on knee osteoarthritis （KOA） and explore whether its protective effect is oriented toward an anti-inflammatory direction by regulation of macrophage polarization， which can effectively inhibit the progression of pathological inflammatory response， reduce the release of inflammatory pain mediators， and downregulate the protein expression level of transient receptor potential vanilloid 1 （TRPV1）， so as to provide experimental evidence for its clinical application and investigate its action mechanism. MethodsAfter adaptive feeding， Sprague-Dawley （SD） rats were randomly divided into six groups： sham group， model group， celecoxib group， and high， medium， and low-dose synovitis granule groups （9.6， 4.8， 2.4 g·kg^-1）. The administration dose of celecoxib capsules was 20 mg·kg^-1. There were 10 rats in the sham group and 12 rats in the model group and each administration group. A KOA animal model was established by means of intra-articular injection of sodium iodoacetate into the knee joint. From the 10^th day of the experiment， each administration group was given intragastric administration at a dose of 10 mL·kg^-1 for 4 weeks. General conditions of rats in each group were assessed daily. The pressure pain threshold （PPT） to mechanical stimulation and joint diameter were recorded. X-ray examination was performed on the right knee joints of rats for imaging analysis. Enzyme linked immunosorbent assay （ELISA） was performed to detect the tumor necrosis factor-α （TNF-α）， serum interleukin-1β （IL-1β）， and other pro-inflammatory cytokines in rat serum samples， as well as the expression levels of neurogenic inflammatory mediators such as nerve growth factor （NGF） and calcitonin gene-related peptide （CGRP）. Histopathological changes in the knee joint synovial tissues were examined by hematoxylineosin （HE） staining. Safranin O-fast green staining was performed to observe and evaluate the degree of knee cartilage lesions. Western blot was employed to quantitatively analyze TRPV1， p38 mitogen-activated protein kinase （p38 MAPK）， and phosphorylated （p）-p38 MAPK in rat knee synovial tissues. Immunofluorescence （IF） was used to measure and assess M1/M2 macrophage polarization. ResultsCompared with those in the sham group， the circumference and joint diameter of the right knee were markedly enlarged in the model group （P<0.01）， while PPTs of rats showed a significant reduction （P<0.01）. The contents of IL-1β， TNF-α， CGRP， and NGF in rats' serum were significantly elevated （P<0.01）， and the synovial Krenn score was increased （P<0.01）. The Mankin score of cartilage tissue was increased （P<0.01）， and the protein expressions of TRPV1 and p-p38 MAPK/p38 MAPK were significantly upregulated （P<0.01）. The experimental intervention significantly reduced the proportion of pro-inflammatory M1 macrophages in the total macrophage population （P<0.01）， and the percentage of M2 macrophages was decreased （P<0.01）. The M1/M2 macrophage ratio was significantly elevated （P<0.01）. Knee joint diameters of all dose groups of Huamoyan granules and the celecoxib group were reduced （P<0.01） compared with those of the model group， and the PPT recovery speeds in the high and medium-dose groups of Huamoyan granules were more obvious （P<0.05）. The contents of IL-1β， CGRP， and NGF in the rats' serum in all administration groups were significantly reduced （P<0.05， P<0.01）， and the content of TNF-α in rats' serum was significantly reduced （P<0.01）. All dose groups of Huamoyan granules demonstrated significant reductions in both synovial Krenn score （P<0.05， P<0.01） and protein expression of TRPV1 and p-p38 MAPK/p38 MAPK in rats' synovial tissues （P<0.01）. The percentage of M1 macrophages in the synovial tissues of the celecoxib group and all dose groups of Huamoyan granules was decreased （P<0.01）. The percentage of M2 macrophages was increased （P<0.05）， and the M1/M2 ratio was decreased （P<0.01）. ConclusionHuamoyan granules can alleviate the inflammatory response of KOA， reduce the release of inflammatory pain mediators， and downregulate TRPV1 protein expression by regulating macrophage polarization. Its mechanism may be related to the TRPV1/p38 MAPK signaling pathway， thereby achieving the effect of improving peripheral pain hypersensitivity in KOA.

ObjectiveTo explore the effect and mechanism of tumor necrosis factor alpha （TNF-α）-regulated circular RNA Williams Beuren syndrome chromosomal region 22 （circWBSCR22） on the malignant behaviors of cervical cancer cells. MethodsHuman cervical cancer HeLa cells were treated with TNF-α. Reverse transcription quantitative polymerase chain reaction （RT-qPCR） was used to detect the expression level of circWBSCR22. Nuclear-cytoplasmic RNA separation experiments were conducted to determine the localization of circWBSCR22 in cells. Cell migration， invasion， viability， and proliferation were assessed through Transwell assay， tetrazolium salt （MTT） assay， and colony formation assay， respectively. Dual-luciferase reporter gene assays were performed to verify the targeting relationship between microRNA-512-5p （miR-512-5p） and circWBSCR22 or family with sequence similarity 60A （FAM60A）. RT-qPCR was used to detect the RNA levels of miR-512-5p and FAM60A. Western blot was used to detect the protein level of FAM60A. ResultsCompared with the Control group， the expression level of circWBSCR22 in HeLa cells treated with TNF-α increased （P<0.05）. About 66% of circWBSCR22 was found in the cytoplasm. Compared with the control group， the migration （P<0.01） and invasion （P<0.01） of HeLa cells transfected with circWBSCR22 were enhanced， but the cell activity and cell proliferation were not significantly affected （P>0.05）. The double luciferase reporter gene assay showed that the relative luciferase activity of the co transfected circWBSCR22-WT and miR-512-5p groups was lower than that of the co transfected circWBSCR22-WT and miR-NC groups （P<0.01）. Compared with the control group， the expression level of miR-512-5p in HeLa cells transfected with circWBSCR22 decreased （P<0.01）. Compared with the control group， the migration （P<0.01） and invasion （P<0.05） ability of HeLa cells transfected with miR-512-5p decreased. Double luciferase reporter gene assay showed that compared with the co transfected FAM60A 3´-UTR-WT and miR-NC groups， the fluorescence activity of the co transfected FAM60A 3´-UTR-WT and miR-512-5p groups decreased （P<0.01）.Compared with the control group， the expression levels of FAM60A mRNA （P<0.05） and protein （P<0.01） in HeLa cells transfected with miR-512-5p decreased. Compared with the control group， the migration （P<0.01） and invasion （P<0.01） of cervical cancer HeLa cells transfected with FAM60A were enhanced. Compared with the control group， the expression levels of FAM60A mRNA （P<0.01） and protein （P<0.05） in the cells transfected with circWBSCR22 increased. The results of rescue experiment showed that compared with the pcDNA+miR-NC group， the expression levels of FAM60A RNA （P<0.01） and protein （P<0.001） in the pcDNA+miR-512-5p group decreased， and the ability of migration （P<0.01） and invasion （P<0.05） decreased； Compared with pcDNA+miR-512-5p group， the expression levels of FAM60A RNA （P<0.01） and protein （P<0.001） in circWBSCR22+miR-512-5p group increased， and the ability of migration （P<0.01） and invasion （P<0.05） was enhanced. ConclusionTNF-α promotes the migration and invasion of cervical cancer cells through the circWBSCR22/miR-512-5p/FAM60A regulatory axis.

ObjectiveTo explore the ethical issues and coping strategies in the diagnosis and treatment of 46, XY disorders of sex development （46, XY DSD） under a multidisciplinary team （MDT） model， and to deepen the understanding of relevant ethical issues while accumulating experience. MethodsA retrospective collection was conducted on the data of children with 46, XY disorders of sex development under a single-center MDT model from January 2017 to December 2024， and the ethical issues involved in the diagnosis and treatment process were analyzed. ResultsA total of 24 MDT discussion documents involving 20 children were collected， including 17 with female social gender and 3 with male social gender. The age ranged from 0.5 to 15.8 years， with children under 8 years accounting for 75%. The ethical issues primarily involved how to ensure adequate informed consent， whether surgery was necessary and its timing， and whether gender selection is reasonable and its timing. Among the 10 children raised as females who completed the gender role psychological scale assessment， 5 demonstrated masculine tendencies， all of whom had pathogenic genetic variants. Furthermore， only 1 patient changed the social gender to male. ConclusionThe diagnosis and treatment of 46, XY DSD is relatively complex， requiring multidisciplinary collaboration. This process involves numerous ethical issues and necessitates adhering to medical ethical principles. Ensuring adequate informed consent is crucial， especially for younger children. The surgery and its timing selection must adhere to the principles of beneficence， non-maleficence， and leaving room for the future. Gender selection constitutes a focus and challenge in diagnosis and treatment. Psychological scales and genetic etiologies are conducive to judgments regarding gender selection， yet multiple factors in the real world may interfere with the gender selection.

Objective: This study investigated the value of multiparametric MRI (mpMRI) in predicting Gleason score (GS) upgrading and downgrading in radical prostatectomy (RP) compared with presurgical biopsy. Materials and Methods: Clinical and mpMRI data were retrospectively collected from 219 patients with prostate disease between January 2015 and December 2021. All patients underwent systematic prostate biopsy followed by RP. MpMRI included conventional diffusion-weighted and dynamic contrast-enhanced imaging. Multivariable logistic regression analysis was performed to analyze the factors associated with GS upgrading and downgrading after RP. Receiver operating characteristic curve analysis was used to estimate the area under the curve (AUC) to indicate the performance of the multivariable logistic regression models in predicting GS upgrade and downgrade after RP. Results: The GS after RP was upgraded, downgraded, and unchanged in 92, 43, and 84 patients, respectively. The AUCs of the clinical (percentage of positive biopsy cores [PBCs], time from biopsy to RP) and mpMRI models (prostate cancer [PCa] location, Prostate Imaging Reporting and Data System [PI-RADS] v2.1 score) for predicting GS upgrading after RP were 0.714 and 0.749, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, tPSA, PCa location, and PIRADS v2.1 score) was 0.816, which was larger than that of the clinical factors alone (P < 0.001). The AUCs of the clinical (age, percentage of PBCs, ratio of free/total PSA [F/T]) and mpMRI models (PCa diameter, PCa location, and PI-RADS v2.1 score) for predicting GS downgrading after RP were 0.749 and 0.835, respectively. The AUC of the combined diagnostic model (age, percentage of PBCs, F/T, PCa diameter, PCa location, and PI-RADS v2.1 score) was 0.883, which was larger than that of the clinical factors alone (P < 0.001). Conclusion Combining clinical factors and mpMRI findings can predict GS upgrade and downgrade after RP more accurately than using clinical factors alone.

The platelets play the important role in tumor angiogenesis,growth,and metastasis,in addition to coagulation.The interaction between tumors and platelets can produce"tumor-induced platelets",which leads various changes of platelet characteristics.In addition,activated platelets can also inhibit the effects of both chemotherapy and immunotherapy,therefore,both inhibiting platelet activation and depleting platelets can effectively improve tumor prognosis.In this review,we intro-duced the key role of platelets in the development of tumors,summarized their application in tumor diagnosis,monitoring,and treatment,and provid-ed our view on how to develop precise delivery strategies based on platelets for achieve efficient and safe tumor treatment.

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 investigate the association between different types of lung nodules and the risk of lung cancer in a population at high risk of lung cancer and to provide an epidemiologic basis for the comprehensive management of lung nodules.Methods:Using the free lung cancer screening program of low-dose CT (LDCT) in Wenling, Zhejiang Province, we collected baseline and imaging information of high-risk groups for lung cancer who underwent LDCT screening from April 2019 to October 2021 and patients with previous history of lung cancer, tuberculosis, pneumoconiosis, and silicosis were excluded. A total of 28 539 study subjects were included in the analysis, and the follow-up ended on 31 December 2023. Based on the characteristics of the detected pulmonary nodules, the study subjects were classified with no nodules, with solid nodules, with pure ground glass nodules, and with part solid nodules groups. The association between different characteristics of lung nodules and the risk of lung cancer development was analyzed using the Cox proportional hazard regression model with a new diagnosis of lung cancer during the follow-up period as the outcome.Results:The overall detection rate of lung nodules with a mean diameter of ≥3 mm was 76.5%, of which 53.7%, 18.2%, and 4.6% were detected in the solid nodule, pure ground glass nodule, and partially solid nodule groups, respectively. There were statistically significant differences between the different nodule groups in terms of age, gender, BMI, history of toxic exposure education level, smoking status, history of lung disease, and family history of lung cancer (all P<0.05). The median follow-up time of the study population was 3.4 years, and 485 new lung cancer cases were diagnosed during the follow-up period. After adjusting for covariates, the results of multifactorial Cox proportional hazard regression model analysis showed that the risk of lung cancer was higher in pure ground glass nodules and part solid nodules compared with solid nodules, with HR values (95% CI) of 1.89 (1.52-2.35) and 6.49 (5.18-8.14), respectively. The results of subgroup analysis showed that patients in the group of part solid nodules had the highest risk of lung cancer in all strata of the population, followed by patients with pure ground glass nodules. Patients in the solid nodule group who were older or had previous lung disease had a higher risk of lung cancer, and the risk of lung cancer in the part solid nodule group differed between genders. Conclusions:The proportion of lung nodules detected is high in the high-risk group of lung cancer, and among them, patients with pure ground glass and part solid nodules have a higher risk of developing lung cancer. Attention should be paid to the annual follow-up management for patients with solid nodules who are older or who have had lung diseases, as well as for female patients with part solid nodules.

Objective To investigate the association of liver radiodensity with the degree and progression of liver fibrosis in patients with chronic hepatitis B(CHB).Methods A retrospective cohort study was conducted among 114 CHB patients who were hospitalized in The First Hospital of Lanzhou University from January to December 2019,and related clinical data were collected,including laboratory tests and abdominal CT.The metabolic characteristics of the patients were assessed,and liver radiodensity was measured.An analysis of variance was used for comparison of normally distributed continuous data between three groups,and the Kruskal-Wallis H rank sum test was used for comparison of continuous data with skewed distribution between three groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between three groups.A logistic regression analysis was used to investigate the influencing factors for the degree of liver fibrosis,and the Cox proportional-hazards regression model analysis was used to investigate the influencing factors for the progression of liver fibrosis in CHB.Results Among the 114 patients enrolled,43(37.72％)had no liver cirrhosis,30(26.32％)were suspected of liver cirrhosis,and 41(35.96％)had liver cirrhosis,with a median follow-up time of 538.5(322.75-1 031.50)days.Liver radiodensity on plain scan(odds ratio[OR]=0.81,95％confidence interval[CI]:0.68-0.97,P=0.025),liver radiodensity on contrast-enhanced scan(OR=0.95,95％CI:0.90-0.99,P=0.037),and liver volume(OR=0.99,95％CI:0.98-0.99,P<0.001)were independent influencing factors for the degree of liver fibrosis.The univariate Cox regression analysis showed that the low level of HDL(hazard ratio=2.81,95％CI:1.04-7.54,P=0.041)was associated with the progression of liver fibrosis in CHB patients,and the degree of liver fibrosis,liver volume,and liver radiodensity showed no significant association with the progression of liver fibrosis(all P>0.05).Conclusion In CHB patients,liver radiodensity is an independent influencing factor for the degree of liver fibrosis,and low HDL has a marked influence on the progression of liver fibrosis.

Cells and exosomes derived from them are extensively used as biological carrier systems. Cells demonstrate superior targeting specificity and prolonged circulation facilitated by their rich array of surface proteins, while exosomes, due to their small size, cross barriers and penetrate tumors efficiently. However, challenges remain, cells' large size restricts tissue penetration, and exosomes have limited targeting accuracy and short circulation times. To address these challenges, we developed a novel concept termed exosomal spheres. This approach involved incorporating platelet-derived exosomes shielded with phosphatidylserine (PS) and linked via pH-sensitive bonds for drug delivery applications. The study demonstrated that, compared with exosomes, the exosomal spheres improved blood circulation through the upregulation of CD47 expression and shielding of phosphatidylserine, thereby minimizing immune clearance. Moreover, the increased expression of P-selectin promoted adhesion to circulating tumor cells, thereby enhancing targeting efficiency. Upon reaching the tumor site, the hydrazone bonds of exosome spheres were protonated in the acidic tumor microenvironment, leading to disintegration into uniform-sized exosomes capable of deeper tumor penetration compared to platelets. These findings suggested that exosome spheres addressed the challenges and offered significant potential for efficient and precise drug delivery.

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