In recent years, precision medicine has made significant progress in the early diagnosis and treatment of Alzheimer′s disease (AD), bringing revolutionary changes to traditional models. In response to these innovative developments, the Chinese Society of Dementia and Cognitive Impairment, starting from the needs of China′s healthcare system and patients, has formulated and released the "Chinese expert consensus on the diagnosis and treatment of mild cognitive impairment due to Alzheimer′s disease 2024". This consensus establishes a systematic and comprehensive diagnostic and therapeutic framework, which not only provides practical guidelines for implementation but also lays a solid foundation for the new stage of precise prevention and treatment of AD. Based on this, in-depth discussions and comments were conducted on AD′s biomarkers, clinical diagnostic criteria, disease staging, and early intervention strategies, aiming to assist clinical and research professionals in constructing a comprehensive AD precision medicine system and to emphasize the importance of early precision recognition and management of the disease, thus advancing early diagnostic and therapeutic efforts for AD into a new era of precision medicine.

OBJECTIVES: Ozone is widely applied to treat allergic skin diseases such as eczema, atopic dermatitis, and contact dermatitis. However, the specific mechanism remains unclear. This study aims to investigate the effects of ozonated oil on treating 2,4-dinitrochlorobenzene (DNCB)-induced allergic contact dermatitis (ACD) and the underling mechanisms. METHODS: Besides the blank control (Ctrl) group, all other mice were treated with DNCB to establish an ACD-like mouse model and were randomized into following groups: a model group, a basal oil group, an ozonated oil group, a FcεRI-overexpressed plasmid (FcεRI-OE) group, and a FcεRI empty plasmid (FcεRI-NC) group. The basal oil group and the ozonated oil group were treated with basal oil and ozonated oil, respectively. The FcεRI-OE group and the FcεRI-NC group were intradermally injected 25 µg FcεRI overexpression plasmid and 25 µg FcεRI empty plasmid when treating with ozonated oil, respectively. We recorded skin lesions daily and used reflectance confocal microscope (RCM) to evaluate thickness and inflammatory changes of skin lesions. Hematoxylin-eosin (HE) staining, real-time PCR, RNA-sequencing (RNA-seq), and immunohistochemistry were performed to detct and analyze the skin lesions. RESULTS: Ozonated oil significantly alleviated DNCB-induced ACD-like dermatitis and reduced the expressions of IFN-γ, IL-17A, IL-1β, TNF-α, and other related inflammatory factors (all P<0.05). RNA-seq analysis revealed that ozonated oil significantly inhibited the activation of the DNCB-induced FcεRI/Syk signaling pathway, confirmed by real-time PCR and immunohistochemistry (all P<0.05). Compared with the ozonated oil group and the FcεRI-NC group, the mRNA expression levels of IFN-γ, IL-17A, IL-1β, IL-6, TNF-α, and other inflammatory genes in the FcεRI-OE group were significantly increased (all P<0.05), and the mRNA and protein expression levels of FcεRI and Syk were significantly elevated in the FcεRI-OE group as well (all P<0.05). CONCLUSIONS Ozonated oil significantly improves ACD-like dermatitis and alleviated DNCB-induced ACD-like dermatitis via inhibiting the FcεRI/Syk signaling pathway.
Animals ; Mice ; Dinitrochlorobenzene/metabolism* ; Skin/metabolism* ; Cytokines/metabolism* ; Interleukin-17/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Dermatitis, Allergic Contact/pathology* ; Dermatitis, Atopic/chemically induced* ; Signal Transduction ; RNA, Messenger/metabolism* ; Mice, Inbred BALB C

Brain metastases are the most common intracranial malignancies, and radiotherapy is an effective treatment of controlling the localized lesions. However, conventional radiotherapy techniques have their own shortcomings that limit the effectiveness of radiotherapy. Metastatic brain tumors are highly likely to recur or progress after treatment. Clinical studies have shown that arginine can penetrate the blood-brain barrier and subsequently improve the radiosensitization of metastatic brain tumors. In this article, the mechanisms underlying the effect of arginine on the radiosensitization of metastatic brain tumors by inhibition of tumor glycolytic metabolism, reduction of DNA damage repair and alteration of tumor hemodynamic parameters were reviewed, aiming to provide new ideas for clinical research and treatment of brain metastases.

Objective:To investigate the effect of liraglutide(LRG) on high glucose-induced oxidative stress injury in(H9c2) cardiomyocytes and its underlying mechanisms.Methods:A high glucose treatment was applied to H9c2 cells for 24 hours to establish an in vitro model of myocardial cell injury. Different concentrations of liraglutide(10, 100, 1000 nmol/L) were administered for intervention. Cell viability was evaluated using the CCK-8 assay, and changes in cell morphology were observed under an inverted microscope. After 24 hours of liraglutide(100 nmol/L) intervention following high glucose treatment, the levels of lactate dehydrogenase(LDH), superoxide dismutase(SOD), and malondialdehyde(MDA) in the cell supernatant were measured. RT-PCR and Western blotting were used to detect the mRNA and protein levels of silent information regulator factor 1(SIRT1) and forkhead box protein O1(FOXO1). Western blotting was also used to assess the acetylation level of FOXO1 protein. Small interfering RNA(siRNA) technology was employed to silence SIRT1 in H9c2 cells to confirm its role in the study. Results:Compared to the control group, the high glucose group showed decreased cell viability, cell structure damage, increased levels of LDH and MDA in the cell supernatant, decreased SOD levels, aggravated oxidative stress, decreased SIRT1 expression, and increased acetylation level of FOXO1(all P<0.05). Compared to the high glucose group, liraglutide intervention resulted in increased cell viability, improved cardiac cell morphology, reduced oxidative stress levels, increased SIRT1 expression, and decreased acetylation level of FOXO1(all P<0.05). When SIRT1 was downregulated, the protective effects of liraglutide were weakened(all P<0.05). Conclusions:Liraglutide has a protective effect against high glucose-induced oxidative stress injury in H9c2 cells, which may be associated with the upregulation of SIRT1 expression.

Objective:To investigate the differences in gene expression levels in knee chondrocytes and chondrons in vitro.Methods:The chondrocytes and chondrons were isolated from full thickness of the 8-months ( n=5) rabbit knees cartilage. Chondrons from right knee were enzymatically isolated using 0.3% dispase and 0.2% collagenase-2 with shaking for 3 hours. Chondrocytes were isolated by 0.4% Pronase and 0.025% collagenase-2 from left knee. The mRNA levels in chondrocytes and chondrons were analyzed by quantitative real-time PCR, including matrix proteins [aggrecan(Agg), collagen(Col-2), Col-6A6, Col-10, Col-11], MMPs and inhibitors (MMP-1, MMP-3, MMP-9, MMP-13, TIMP-1, TIMP-2, TIMP-3), cytoskeletal proteins (Sox-9, vinculin, tubulin, actin), cytokines (IL-β, TNF-α). Analysis was performed using SPSS 16.0 statistical software, and the two-group comparisons were considered as significant by t-test at P<0.05. Results:Compared to the chondrocytes, the Agg [(5.78±0.90) vs (1.89±0.27), t=9.26, P<0.001], Col-2 [(6.29±0.76) vs (3.06±0.60), t=7.46, P<0.001], Col-6A6 [(0.89±0.18) vs (0.22±0.06), t=7.90, P<0.001], Col-10 [(3.83±0.76) vs (1.00±0.26), t=7.88, P<0.001] and TIMP-1 [(1.98±0.85) vs (1.03±0.34), t=2.32, P=0.049], TIMP-2[(3.46±1.50) vs (1.52±1.06), t=2.36, P=0.046], TIMP-3 [(3.96±0.50) vs (1.36±0.18), t=10.94, P<0.001], Sox-9 [(7.09±2.93) vs (3.24±0.77), t=2.84, P=0.022], vinculin [(3.42±1.69) vs (1.46±0.68), t=2.41, P=0.043], tubulin[(9.34±0.71) vs (2.35±0.80), t=14.61, P<0.001] showed higher expression in the chondrons. Compared to the chondrocytes, the MMP-1 [(1.02±0.30) vs (2.67±0.45), t=6.91, P<0.001], MMP-3 [(1.21±0.32) vs (2.52±0.79), t=3.44, P=0.009], MMP-13 [(1.23±0.34) vs (3.42±0.86), t=5.30, P=0.007], IL-1β [(1.02±0.14) vs (2.70±0.49), t=7.37, P<0.001], TNF-α [(0.99±0.08) vs (3.15±0.54), t=8.85, P<0.001] showed lower expression in the chondrons. There were no difference between chondrons and chondrocytes for Col-11, MMP-9, actin ( P>0.05). Conclusion:The gene expression of extracellular matrix components are higher and the gene expression levels of inflammatory factors and MMPs are decreased in chondrons compared with the chondrocytes, suggesting the chondrons have more multiplication potential as seeding cells for tissue-engineered cartilage.

Long non-coding RNA (lncRNA) contains rich information and functions. The research on Traditional Chinese Medicine (TCM) targeting lncRNA mainly involves tumors, cardiovascular diseases, endocrine and metabolic related diseases, osteoporosis and other diseases, which are used to explore the mechanism of TCM and the differetiation of TCM syndromes or constitution, etc. LncRNA has important application prospects in the field of TCM. The study of lncRNA may provide new ways and technical methods for the research of modern TCM.

OBJECTIVE: To explore mutational characteristics of acute myeloid leukemia (AML) patients with CBFβ-MYH11⁺ and analyze the correlation between the mutations and partial clinical characteristics. METHODS: A total of 62 AML patients with CBFβ-MYH11⁺ were included and 51 candidate genes were screened for their mutations using targeted next-generation sequencing (NGS). The exon 12 of NPM1 , FLT3-ITD , and TAD, bZIP domains of CEBPA were detected by genomic DNA-PCR combined with sanger sequencing. RESULTS: Compared with RUNX1-RUNX1T1 ⁺ group, the patients with CBFβ-MYH11⁺ showed higher age, peripheral WBC level, initial induced complete remission (CR) rate, more commonly carried chromosomal abnormalities such as +22, and lower deletion ratio of sex chromosome (-X or -Y) (P<0.05). In AML patients with CBFβ-MYH11⁺, the most common mutation was NRAS , followed by KIT, KRAS , and FLT3-TKD . Compared with RUNX1-RUNX1T1⁺ group, NRAS and FLT3-TKD were more frequently mutated in patients with CBFβ-MYH11⁺ (51.6% vs 18.7%, 17.7% vs 3.8%) (P<0.05). CONCLUSION The genomic landscape and clinical characteristics of AML patients with CBFβ-MYH11⁺ are different from patients with RUNX1-RUNX1T1 ⁺.
Humans ; Genomics ; Leukemia, Myeloid, Acute/genetics* ; Myosin Heavy Chains

Objective:To comprehensively evaluate the clinical application status of oral movement intervention in preterm infants, analyze the obstacles in the process of clinical application of the best evidence and formulate countermeasures, so as to provide reference for clinical evidence transformation.Methods:Based on the theoretical guidance of the "Clinical Application Model of Evidence" of the Joanna Briggs Institute (JBI) Evidence-Based Health Care Center in Australia, 12 pieces of the best evidence for oral movement intervention in premature infants were included, and 13 review indicators were formulated. From May to July 2021, a status review was conducted in Department of Neonatology in Suzhou Hospital Affiliated to Nanjing Medical University. The Ottawa Model of Research Use (OMRU) was used to analyze the barriers and facilitators in the process of evidence application and formulate effective intervention strategies and action plans.Results:Among the 13 reviewed indicators, only 2 items had a compliance rate of 100%, 2 items had a compliance rate of more than 60%, 6 items had a compliance rate of less than 60%, and 3 items had a compliance rate of 0. The main obstacle factors were lack of standardized process and assessment tools, lack of oral motor intervention related knowledge and training for preterm infants, increased clinical workload due to evidence transformation and the low level of knowledge and action among medical staff. The main promoting factors were support from managers for the development and reform of evidence-based learning, good learning atmosphere for doctors and nurses, departments with material and hardware conditions for evidence transformation, effective evidence, and parents' willingness to accept the reform. Through analysis, countermeasures were drawn up to formulate feasible and suitable standardized procedures and introduce assessment tools. Managers formulated and implemented incentive policies, adopted various training methods, strengthened quality supervision in the process of evidence transformation, timely gave feedback of progress results and improved human resource allocation.Conclusions:There is a certain gap between the best evidence of oral movement intervention in premature infants and the current clinical nursing practice. It is necessary to formulate corresponding countermeasures according to the obstacle factors and promoting factors, promote the evidence transformation and constantly promote the evidence-based practice of oral movement intervention in premature infants.

Objective: To study the adaptive response and time effect of A549 cell apoptosis induced by low-dose X-ray irradiation, and to preliminarily explore the possible mechanism of adaptive effect.  Methods: A549 cells were irradiated with X-ray of 50 mGy, 200 mGy and 500 mGy, respectively, and then irradiated with an effect dose of 20 Gy after intervals of 3 h, 6 h, 12 h, 24 h and 48 h, respectively, for cell apoptosis detection. The cell cycle distribution and DNA damage were detected after an interval of 6 h between the initial dose and the effect dose. 20 Gy and 0 Gy were set as the control. Results: After irradiation at 20 Gy at intervals of 3 h, 6 h, 12 h and 24 h from the low- dose irradiation, the apoptosis rates of the 50 mGy～20 Gy, 200 mGy～20 Gy, and 500 mGy~ 20 Gy groups were significantly lower than that of the 20 Gy group (P < 0.05); after an interval of 48 h, there was no significant difference in the apoptosis rate between the 50 mGy～20 Gy, 200 mGy～20 Gy, and 500 mGy～20 Gy groups and the 20 Gy group. After an interval of 6 h between the low-dose irradiation and the effect dose irradiation, the percentage of cells at G0/G1 phase in the 50 mGy～20 Gy and 200 mGy～20 Gy groups was significantly lower than that in the 20 Gy group (P < 0.05); the percentage of cells at G2/M phase in the 50 mGy～20 Gy and 200 mGy~20 Gy groups were significantly reduced compared with the 20 Gy group (P < 0.05). There was no significant difference in the percentage of cells at G0/G1 and G2/M phases between the 500 mGy～20 Gy and 20 Gy groups. Compared with the 20 Gy group, the cell DNA damage in the 50 mGy～20 Gy, 200 mGy～20 Gy and 500 mGy~20 Gy groups were decreased, but without significant difference.  Conclusion Low-dose X-ray irradiation can induce the adaptive response of A549 cells apoptosis, which is related to the time interval between the initial dose and the effect dose. The adaptive effect may be related to the changes in cell cycle induced by low-dose X-ray.

Tricuspid regurgitation (TR) interventions are under rapid development. The K-Clip? system is the first domestic transcatheter tricuspid annuloplasty system with unique clamping procedure to achieve annular reduction.Intraoperative echocardiographic monitoring procedures for transcatheter tricuspid annuloplasty have not been reported yet in China. Thus, this review aimed to propose the standard two-dimensional and three-dimensional transesophageal echocardiographic workplanes and procedures to guide and monitor the implantation of K-Clip system based on our experience in Zhongshan Hospital, Fudan University to provide a reference point for the intraoperative echocardiographic monitoring of future transcatheter tricuspid annuloplasty devices in China.