[摘 要] 甲状腺癌是内分泌系统中最为常见的恶性肿瘤，近年来其发病率呈现出显著的上升趋势。乙酰化修饰作为一种重要的蛋白质翻译后修饰，参与调控各个类型甲状腺癌相关基因的转录表达、细胞周期进程及侵袭能力。组蛋白去乙酰化酶（HDAC）抑制剂在甲状腺癌治疗中显示出潜在的应用前景。本文通过调研近年来相关文献，系统回顾了乙酰化修饰在参与甲状腺癌发生发展过程中的生物学功能及其调控机制，进一步探讨HDAC抑制剂在临床治疗中的应用前景，为甲状腺癌的靶向治疗提供坚实的理论依据和提出可行的治疗策略。

Objective To explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP＜20 ng/mL, DCP＜40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P＜0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P＜0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.

Objective To explore the correlation of MET status in patients with advanced prostatic acinar adenocarcinoma with the clinical pathological parameters and prognosis. Methods The specimen from 135 patients with advanced prostatic acinar adenocarcinoma was included. The expression of c-MET protein was detected via immunohistochemistry, and MET gene amplification was assessed by fluorescence in situ hybridization. The relationships of c-MET expression and gene amplification with clinicopathological features and prognosis were analyzed. Results The positive expression rate of c-MET was 52.60% (71/135). Compared with the c-MET expression in adjacent tissues, that in tumor tissues showed lower heterogeneous expression. Among the cases, 1.71% (2/117) exhibited MET gene polyploidy, but no gene amplification was detected. Positive c-MET expression was significantly correlated with high Gleason scores and grade groups (P=0.0073). However, no significant relationship was found between c-MET expression and progression-free survival or post-treatment t-PSA levels. Conclusion c-MET protein is expressed at a relatively low level in advanced prostatic acinar adenocarcinoma, suggesting that c-MET may not be a viable target for ADC drug development in prostatic acinar adenocarcinoma.

This study selected 6 529 plant-based Chinese materia medica(PCMM) from Chinese Materia Medica as research subjects and applied a random permutation test to explore the overall correlation characteristics between nature and flavor, as well as the correlation characteristics after distinguishing different medicinal parts and harvest seasons. The results showed that the overall correlation characteristics between nature and flavor in PCMM were significantly associated in the following pairs: cold and bitter, cool and bitter, cool and astringent, cool and light, neutral and sweet, neutral and astringent, neutral and light, neutral and sour, hot and pungent, and warm and pungent. When analyzing the data by distinguishing medicinal parts and/or harvest seasons, new correlation patterns emerged, characterized by the disappearance of some significant correlations and the emergence of new ones. When analyzing by medicinal parts alone, significant correlations were found in the following cases: cold and light in leaves, cold and salty in barks, cool and sweet in fruits and seeds, neutral and pungent in whole herbs, neutral and salty in stems, and warm and salty in flowers. However, no significant correlations were found between cool and bitter in stems and other types of herbs, cool and astringent in fruits, seeds, flowers, and other types of herbs, cool and light in leaves, fruits, seeds, barks, flowers and other types of herbs, neutral and sweet in barks, neutral and astringent in whole herbs and stems, neutral and light in leaves, fruits, seeds, and flowers, neutral and sour in whole herbs, stems, barks, flowers, and other types of herbs, and hot and pungent in whole herbs, stems, flowers, and other types of herbs. When analyzing by harvest season alone, significant correlations were found in the following cases: cold and salty, and cool and sour in herbs harvested in winter, and neutral and salty in herbs harvested year-round. However, no significant correlation was found between cool and light in herbs harvested in winter. When considering both medicinal parts and harvest seasons, compared to the independent influence of medicinal parts, 14 new significant correlations emerged(e.g., the correlation between cool and bitter in stems harvested in spring), while 53 previously significant correlations disappeared(e.g., the correlation between cool and bitter in barks harvested in summer). Compared to the independent influence of harvest seasons, 11 new significant correlations appeared(e.g., the correlation between cold and light in barks harvested in autumn), while 50 previously significant correlations disappeared(e.g., the correlation between hot and pungent in leaves harvested in winter). This study is the first to reveal the influence of medicinal parts and harvest seasons on the correlation between nature and flavor in PCMM, which highlights that these two factors can interact and jointly affect nature-flavor correlations. Further research is needed to explore the underlying mechanisms. This study provides a deeper understanding of the inherent scientific connotations of herbal properties and offers a theoretical foundation for the cultivation and harvesting of PCMM.
Seasons ; Plants, Medicinal/growth & development* ; Drugs, Chinese Herbal/chemistry* ; Taste

OBJECTIVE: To assess the mid-term clinical efficacy of the direct anterior approach for window decompression and bone grafting surgery in the treatment of early to mid-stage osteonecrosis of the femoral head (ONFH). METHODS: A retrospective analysis was performed on 40 patients (40 hips) diagnosed with osteonecrosis of the femoral head (ONFH), classified as types L1 and L2 according to the China-Japan Friendship Hospital (CJFH) classification system, and at stagesⅡ, ⅢA, and ⅢB based on the Association Research Circulation Osseous (ARCO) staging system. All patients underwent head-neck junction fenestration decompression and bone grafting via the direct anterior approach between January 2015 and May 2022, with complete follow-up data available for a minimum of three years. The ages of the patients ranged from 35 to 69 years old, with a mean of (49.13±6.14 ) years old;their body mass index (BMI) ranged from 20.02 to 27.94 kg·m^-2, with a mean of (23.65±1.69) kg·m^-1;the duration of the disease ranged from 13 to 36 months, with a mean of (24.55±4.14) months. Preoperative and 3-year postoperative X-ray parameters were collected, including the anterior preserved angle(APA), lateral preserved angle (LPA), and combined preserved angle (CPA). Additionally, hip joint disability and osteoarthritis outcome scores (HOOS) and Harris hip scores (HHS) were recorded. RESULTS: Forty patients were followed up for a period ranging from 36 to 59 months, with a mean duration of (47.18±6.18) months. At 3 years postoperative, none of the patients underwent hip replacement surgery. The APA (73.15±19.35)°, LPA (75.35 ±21.48)°, and CPA (136.25±26.78)° at the 3-year postoperative significantly improved compared to preoperative measurements (61.93±20.54)°, (59.46±22.67)°, and (116.58±32.47)°, with statistical significance (P<0.05). The HOOS (20.37±1.39) and HHS (89.74±3.28) scores at the 3-year postoperative were significantly improved from preoperative scores (12.36±1.58) and (50.27±6.15), respectively, with statistical significance (P<0.05). CONCLUSION The direct anterior approach for window decompression and bone grafting surgery can relieve joint pain, improve joint function, and enhance X-ray preserved angles, effectively preventing femoral head collapse, making it an effective surgical method for treating ONFH classified as L1, L2 according to CJFH and stagesⅡ, ⅢA, ⅢB according to ARCO.
Humans ; Middle Aged ; Male ; Female ; Adult ; Decompression, Surgical/methods* ; Bone Transplantation ; Femur Head Necrosis/surgery* ; Follow-Up Studies ; Aged ; Retrospective Studies

Complex crown-root fractures in the esthetic zone refer to a type of dental trauma occurring in the anterior region, characterized by concurrent fractures involving both the crown and the root, with associated pulp exposure and periodontal tissue injury. These injuries consistently exhibit critical anatomical features, including a fixed palatal fracture location below the alveolar crest, compromised residual tooth structure, and frequent encroachment of the biological width. To predict treatment outcomes, a risk assessment framework based on the restoration-tooth-periodontium interface was developed. Resistance risk was evaluated by assessing the type of residual dentin ferrule and the length of the root within the alveolar bone, while periodontal risk was assessed according to gingival phenotype and alveolar bone morphology. Based on these risk dimensions and the principles of aesthetics, stability, and minimally invasive treatment, a diagnostic classification system was established to categorize fractures into three types: favorable, intervention and high-risk. Type-specific management strategies were proposed: for favorable cases, crown lengthening combined with deep margin elevation to reduce periodontal risk is recommended; for intervention cases, orthodontic extrusion or surgical extrusion is applied to simultaneously address both ferrule deficiency and biological width violation; for high-risk cases, extraction followed by implant restoration is advised due to limited root preservation value. The presented classification enables clinicians to adopt a scientific and structured approach to treatment planning for these complex crown-root fractures in the aesthetic zone.
Humans ; Tooth Fractures/therapy* ; Tooth Root/injuries* ; Risk Assessment ; Tooth Crown/injuries* ; Periodontium ; Esthetics, Dental ; Dental Restoration, Permanent/methods*

OBJECTIVE: To summarize the relevant evidence of testicular cancer patients' fertility management which provides a basis for fertility guidance for young testicular cancer patients. METHODS: The evidence, guidelines, expert consensus, evidence summary, systematic review and Meta-analysis on fertility-related clinical decision-making were searched from computer decision support systems, relevant guideline websites, evidence-based databases, original research databases, and professional association websites at home and abroad. The search period was set dating from the establishment of the database to July 2024. Two researchers with evidence-based nursing research background independently completed the quality evaluation, evidence extraction and summary of the literature. RESULTS: A total of 21 articles were selected, including 4 clinical decisions, 8 guidelines, 4 expert consensuses, 3 systematic reviews and 2 Meta-analyses. Thirty-three pieces of best evidence from six aspects were summarized, including fertility assessment, fertility counseling, fertility preservation timing, fertility preservation regimen, anti-tumor therapy and fertility, and contraceptive timing. CONCLUSION The best evidence summarized in this study provides a basis for clinical medical staff to carry out fertility management in testicular cancer patients. In clinical application, medical staff need to fully consider the patient's wishes in combination with the clinical situation, and promote the maximum benefit of the patient, so as to further improve the life quality of the patients.
Humans ; Male ; Evidence-Based Medicine ; Fertility ; Fertility Preservation ; Testicular Neoplasms/therapy* ; Systematic Reviews as Topic

OBJECTIVES: To explore the role of oxidative stress and immune infiltration in rheumatoid arthritis (RA). METHODS: RA datasets GSE55235 (10 RA vs 10 normal samples) and GSE55457 (13 RA vs 10 normal samples) from the GEO database were merged as the test set to identify the differentially expressed genes (DEGs) in RA using R. The DEGs were intersected with oxidative stress-related genes to obtain oxidative stress-associated DEGs. KEGG and GO enrichment analyses of the DEGs were performed, and the RA-related pathways and biological processes were analyzed using GSEA. A protein-protein interaction (PPI) network was constructed using STRING and Cytoscape, and the top 10 key genes were obtained using the Degree algorithm. The validation dataset GSE1919 from GEO database was used for ROC analysis of the key genes to obtain the core genes, and their correlations with infiltrating immune cells were analyzed using CIBERSORT. The results were verified by RT-qPCR for detecting expression levels of the core genes in RA and normal joint samples. RESULTS: We identified 89 oxidative stress-associated DEGs. Enrichment analysis suggested that these DEGs were involved in the biological processes including oxidative stress, chemical stress response, reactive oxygen species response, and lipopolysaccharide response. ROC analysis showed that the 5 core genes (STAT1, MMP9, MYC, CCL5, and JUN) all had AUC values >0.7, indicating their high diagnostic sensitivity and specificity for RA. These genes were closely correlated with immune cells, particularly T cells. RT-qPCR confirmed significant differential expressions of the core genes between RA and normal samples. CONCLUSIONS Oxidative stress and diverse immune responses are features of RA, and the immune responses contribute to activation of oxidative stress. The identified core genes can potential serve as new diagnostic markers for RA.
Arthritis, Rheumatoid/genetics* ; Oxidative Stress/genetics* ; Humans ; Computational Biology ; Protein Interaction Maps ; Gene Expression Profiling ; Gene Regulatory Networks

The Split-Cre system consists of two inactive polypeptides: NCre and CCre, which can be recombined into an active full-length Cre under certain conditions. This system is typically used with LoxP. To develop an efficient Split-Cre system, this study used Rma intein from Rhodothermus marinus to split Cre and screened out the split site S102 which could efficiently mediate the recombination of Cre in the "Traffic Light" reporter cell line. Moreover, the S102 Split-Cre system was delivered to mice by dual-adeno-associated virus (AAV), and it was demonstrated that the efficiency of the Rma intein-mediated S102 Split-Cre system was comparable to the full-length Cre in mice. This system lays a foundation for both basic and applied research on Split-Cre.
Inteins/genetics* ; Animals ; Integrases/biosynthesis* ; Mice ; Dependovirus/metabolism* ; Bacterial Proteins/genetics* ; Recombination, Genetic ; Humans

Severe asthma stands as a formidable contributor to both mortality and morbidity of pa-tients suffering asthma,casting substantial social and economic shadows on communities.As our un-derstanding of asthma's pathophysiology deepens,a beacon of hope emerges in the form of biological targeted therapies,offering a promising avenue for the management of this challenging condition.These therapies,by precisely inhibiting or modulat-ing pivotal molecules in the inflammatory cascade,offer potential benefits in symptom alleviation,lung function enhancement,and risk reduction of acute exacerbations.They signify a paradigm shift in severe asthma treatment.Within the confines of this article,we embark on a systematic exploration of the immunological underpinnings that define se-vere asthma.By delving into the intricacies of the immune system's role in exacerbating this condi-tion,we aim to offer a comprehensive assessment of both the current landscape and the future pros-pects of biological therapies.Our objective is to provide a scientifically robust and valuable refer-ence that can guide the individualized treatment of patients grappling with severe asthma.