[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.

NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD⁺), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD⁺ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD⁺ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.
Humans ; NAD/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Nicotinamide Phosphoribosyltransferase/metabolism* ; Cytokines/metabolism* ; Quinones ; Oxidoreductases

Severe asthma stands as a formidable contributor to both mortality and morbidity of patients suffering asthma, casting substantial social and economic shadows on communities. As our understanding 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 modulating 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 severe asthma. By delving into the intricacies of the immune system's role in exacerbating this condition, we aim to offer a comprehensive assessment of both the current landscape and the future prospects of biological therapies. Our objective is to provide a scientifically robust and valuable reference that can guide the individualized treatment of patients grappling with severe asthma.

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.

Objective:To analyze the changes of diagnosis and treatment before and after renal biopsy in adult patients with acute kidney disease (AKD), and to explore the value of renal biopsy in the diagnosis and treatment of AKD.Methods:It was a single-center retrospective observational study. The adult patients with AKD who underwent renal biopsy in the Department of Nephrology of the First Affiliated Hospital of Nanjing Medical University from January 1, 2017 to December 31, 2021 were enrolled. Demographic data, general clinical data, laboratory tests, and diagnosis and treatment data before and after renal biopsy were collected to analyze the concordance rate between clinical and pathological diagnoses, changes in treatment after renal biopsy, and bleeding complication.Results:A total of 575 patients diagnosed with AKD by renal biopsy were included in this study, with age of 51 (36, 63) years old and 359 males (62.4%). Among them, there were 293 patients (51.0%) of acute kidney injury, 348 patients (60.5%) of hypertension and 124 patients (21.6%) of diabetes. The peak serum creatinine was 272 (190, 477) μmol/L. The hemoglobin was 106 (86, 126) g/L. The 24-hour urine protein was 2.15 (0.79, 4.82) g. There were 347 patients (60.3%) of acute glomerular diseases, 136 patients (23.7%) of acute interstitial nephritis, 47 patients (8.2%) of thrombotic microangiopathy, and 45 patients (7.8%) of acute tubular necrosis. The most common types of acute glomerular diseases were IgA nephropathy and anti-neutrophil cytoplasmic antibody-associated glomerulonephritis, accounting for 22.3% (128/575) and 12.2% (70/575), respectively. The clinical diagnoses before renal biopsy were consistent with the renal histopathological diagnoses in 454 patients, with an accuracy rate of 79.0%. Following the renal biopsy, the treatment plan involving glucocorticoids or immunosuppressants was adjusted in 394 patients (68.5%). Significant post-biopsy bleeding occurred in 15 patients (2.6%), with 12 patients requiring blood transfusion and 1 patient requiring surgical intervention.Conclusions:Twenty-one clinical diagnoses do not match the pathological diagnoses in adult AKD patients, 68.5% of patients have changes in their treatment plans, and 2.6% of patients have significant hemorrhagic complications after renal biopsy. Clinicians need to carefully consider the benefits and risks and make individualized decisions about renal biopsy.

italic>Lamiophlomis rotata is an important medicinal plant species endemic to the Tibetan Plateau, which is prone to strong climate change impacts on its habitable range due to the high sensitivity of the Tibetan Plateau to climate change. Accurate quantification of species vulnerability to climate change is essential for assessing species extinction risk and developing effective conservation strategies. Therefore, we carried out the α-shape analysis to determine the habitat of L. rotata. We then carried out the climate-niche factor analysis (CNFA) to assess the vulnerability of L. rotata to climate change based on five climate variables (i.e., mean diurnal range, temperature seasonality, mean temperature of warmest quarter, precipitation of driest month and precipitation of warmest quarter) in the context of two shared socioeconomic pathways (i.e., SSP126 and SSP585) and three global climate models (CMCC-ESM2: Centro Euro-Mediterraneo sui Cambiamenti Climatici-Earth System Model version 2; HadGEM3-GC31-LL: Hadley Global Environment Model version 3-Global Coupled configuration 3.1; IPSL-CM6A-LR: Institut Pierre Simon Laplace-Climate Model version 6) during two different periods (2041-2060 and 2081-2100). The vulnerability of L. rotata to climate change was calculated by integrating the sensitivity and exposure indices of L. rotata to five climate variables. The results showed that L. rotata had the highest vulnerability to the precipitation of warmest quarter. Its vulnerability within its habitat range generally showed a spatial pattern of high value in the southern region and low in the northern region, high in the western region and low in the eastern region. In general, the vulnerability of L. rotata under the SSP585 scenario was higher than that under the SSP126 scenario. The climate data of different global climate models have some influence on the results, while the resulted uncertainty can be reduced by data integration methods. As a result of climate change, the pressure on the survival of L. rotata in the future will be intensified in the low-altitude areas such as the Yarlung Zangbo River, Yigongzangbu River, Zayu River, and Jiaomuzu River, etc., while the highly weathered scree flats or stony alpine meadows in the high-altitude zones, such as the eastern Tanggula Mountain Range, the northern part of Hengduan Mountain Range, and the western part of the Qinling Mountains, may become its refuge. It is necessary to focus on and strengthen the protection and management of L. rotata resources in these vulnerble and critical areas.

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.

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.