Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m¹A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m¹A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.

Purpose To elucidate the clinicopathological characteristics of primary malignant giant cell tumor of bone(PMGCTB)with mainly osteosarcoma-like morphology.Meth-ods Clinicopathologic features of 7 cases of PMGCTB were ret-rospectively analyzed.Results Among 7 patients with PMGCTB,there were 4 females and 3 males,aged between 9 and 66 years(mean age 39.5 years,median age 35 years).The distal femur emerged as the most frequent site to be involved(3/6).The main clinical manifestations included pain and swelling at the original site of the tumor.Radiological findings indicated osteolytic lesions,often combined with sclerotic areas;most ca-ses showed cortical bone destruction and soft tissue masses(5/7).Histologically,the majority of tumors exhibited typical mor-phological features of osteosarcoma with a few or without osteo-clast-like multinucleated giant cells.Positive immunoreaction with H3F3A G34W was confirmed in 6 cases and with H3F3A G34V in 1 case.SATB2 and p63 were positive in all cases,p53 was proved to be wild type,the Ki67 proliferation index ranged approximately from 10％to 50％.H3F3A p.G34W mutation was detected in 6 cases and only 1 case harboring H3F3A p.G34V mutation.Conclusion PMGCTB is exceedingly rare and difficult for accurate diagnosis,especially for those with atypical morphological features.A comprehensive analysis involving ra-diological,immunophenotypic,and molecular detection is neces-sary to rule out other high-grade sarcomas.

Objective:To investigate the clinicopathological characteristics of giant cell tumor of bone (GCTB) in children.Methods:A total of 35 cases of GCTB diagnosed at Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiaotong University School from 2016 to 2023 were collected, and a retrospective analysis of clinicopathological features and imaging findings was conducted.Results:Pediatric GCTB accounted for approximately 4.6% of total GCTB cases during the study period. There were 11 males and 24 females. The onset age ranged from 9 to 18 years (mean age 15 years, median age 16 years), with 8 cases (8/35, 22.9%) experiencing postoperative recurrence. Twenty-eight cases (28/35, 80%) primarily affected long bones, while 7 cases involved small or irregular bones. Imaging revealed osteolytic changes as the predominant feature, with 3 cases exhibited open physis, one of which had the tumor primarily at the diaphysis without crossing the physis. Histologically, pediatric GCTB resembled adult cases, characterized by mononuclear cells and osteoclast-like giant cells. Seven cases with denosumab treatment demonstrated degrees of giant cell disappearance, increased fibrous tissue and reactive bone proliferation in the stroma. One case was diagnosed as pediatric multicentric GCTB, and three cases as pediatric primary malignant GCTB, with malignant transformation into osteosarcoma. In all 35 cases, mutations in the H3F3A gene were identified, comprising 32 cases with H3.3 p.G34W mutations, one case with H3.3 p.G34V mutation, and 2 cases with H3.3 p.G34L mutations. Notably, the former two categories were successfully validated at the protein level through immunohistochemical staining, utilizing highly specific antibodies tailored for these mutation types: H3.3 p.G34W antibody and H3.3 p.G34V antibody. However, immunohistochemical staining was not available for the last category.Conclusions:Pediatric GCTB predominantly affects females and occurs primarily in long bones, mainly around the knee joint, the majority of tumors predominantly arise in the epiphysis and extend into the metaphysis; however, in cases where the epiphyseal plates are still unclosed, the tumors may be restricted to the metaphysis. Detection of H3F3A gene mutation is crucial for the diagnosis and differential diagnosis of pediatric GCTB.

Objective:To explore the effects of the scaffolding-based flipped classroom approach in the teaching of Infectious Disease Nursing. Methods:We assigned 152 students of nursing and midwifery majors of grade 2018 (experimental group) to be taught using the scaffolding-based flipped classroom approach and 182 students of grade 2017 (control group) to be taught using the traditional lecture method. Teaching effects were evaluated through students' exam performance and a questionnaire survey. Numerical data were analyzed using the χ2 test and t test with the use of SPSS 18.0, and text data were processed using NVivo 11 for thematic analysis. Results:The experimental group and control group showed significant differences in the interim exam score (83.19±7.96 vs. 79.62±3.14, P<0.001) and final exam score (78.47±6.92 vs. 73.16±8.24, P<0.001). The students of grade 2018 had a high level of participation in online learning. The questionnaire results showed that the scaffolding-based flipped classroom was well recognized in terms of students' overall perception, perceived course quality, perceived value of learning, and satisfaction and the open-ended question, with low scores for learner complaints and loyalty. Conclusions:The scaffolding-based flipped classroom is feasible in the teaching of Infectious Disease Nursing, which can improve students' academic performance and overall competence.

Objective To investigate the effect of Liraglutide on alleviating the liver injury inmice with DM,and to evaluate the effects of Liraglutide on liver fibrosis,liver aging and liver oxidative stress.Methods Thirty C57BL/6J mice were randomly divided into normal control group(Con),model group(Mod)and Liraglutide group(Lir),with 10 mice in each group.The expressions of p21,p16,p53,inflammatory factors TNF-α and IL-1β were detected by Western blot.The effects of Liraglutide on liver fibrosis were analyzed by Masson and Sirius scarlet staining.The oxidative stress Lndexes of reactive oxygen species(ROS),superoxide dismutase(SOD)and malondialdehyde(MDA)were compared among the groups.Results The expressions of TNF-α,IL-6,IL-1β,NLRP3,p16,p21,p53,p15,TNF-α,IL-6,IL-1β,NLRP3 and α-SMA were higher in Mod group than in Con and Lir groups(P<0.05).ROS and MDA were higher,while SOD and GSH-PX were lower in Mod group than in Con and Lir group(P<0.05).The positive areas of Sirius scarlet and Masson staining were higher in Mod group than in Con and Lir groups(P<0.05).Conclusions Liraglutide can alleviate liver aging,inflammation and fibrosis,and has protective effect on liver injury caused by DM.

Energy metabolism is fundamental for life.It encompasses the utilization of carbohydrates,lipids,and proteins for internal processes,while aberrant energy metabolism is implicated in many diseases.In the present study,using three-dimensional(3D)printing from polycarbonate via fused deposition modeling,we propose a multi-nuclear radiofrequency(RF)coil design with integrated 1H birdcage and interchangeable X-nuclei(2H,13C,23Na,and 31P)single-loop coils for magnetic resonance imaging(MRI)/magnetic resonance spectroscopy(MRS).The single-loop coil for each nucleus attaches to an arc bracket that slides unrestrictedly along the birdcage coil inner surface,enabling convenient switching among various nuclei and animal handling.Compared to a commercial 1H birdcage coil,the proposed 1H birdcage coil exhibited superior signal-excitation homogeneity and imaging signal-to-noise ratio(SNR).For X-nuclei study,prominent peaks in spectroscopy for phantom solutions showed excellent SNR,and the static and dynamic peaks of in vivo spectroscopy validated the efficacy of the coil design in structural imaging and energy metabolism detection simultaneously.

Missed diagnosis can often be noted in mild traumatic brain injury (mTBI), resulting from atypical symptoms, diverse performances and subjectively dependent report. Blood biomarkers can not only reflect the pathophysiological process of mTBI to a certain extent, but also have important clinical value in assessing brain injury severity and predicting adverse outcomes. This article systematically describes the research progress of blood biomarkers that can assist mTBI diagnosis, distinguish CT manifestations and predict prognoses in recent years, aiming to provide references for clinical application of blood biomarkers in mTBI.

With the acceleration of population aging and the continuous growth of the elderly population,frailty has become a global public health problem.At the same time,an increasing number of elderly people require surgical treatment,and people are paying more attention to the possible postoperative neurocognitive disorder.Frailty and neurocognitive disorder interact with each other,forming a vicious cycle.Improving one of them can improve the prognosis of the elderly.As one of the commonly used anesthetic drugs in clinical practice,dexmedeto-midine has neuroprotective effects.This article reviews the relationship between frailty and neurocognitive disorder,as well as the research progress of dexmedetomidine in improving perioperative neurocognitive disorder in frail elderly patients.

Organoids can well simulate the heterogeneity of tumors,including tumor microenvironment and immune response,which helps to more accurately predict patient responses to drug and treatment effects.Organoids can be used for drug screening before drugs enter body,thus reducing the time and cost of clinical trials.However,research on tissue-organoids still faces some challenges,such as technical limitation and ethical issue.This review mainly introduces the progress in the research of breast cancer organoids,including the definition of organoids,development history,advantages and application in breast cancer research.

Objective:To investigate the predictive value of a clinical imaging model based on multi-slice helical computer tomography (MSCT) examination in predicting prognosis of advanced gastric adenocarcinoma.Methods:The retrospective cohort study was conducted. The clinicopatho-logical data of 88 patients with advanced gastric adenocarcinoma who were admitted to the Ningbo Yinzhou No.2 Hospital from January 2019 to January 2021 were collected. There were 62 males and 26 females, aged (60±15)years. All patients underwent preoperative MSCT examination. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were expressed as absolute numbers. Univariate and multivariate analyses were conducted using the Logistic regression model. The receiver opera-ting characteristic curve was used to analyze the predictive efficacy of prognosis, and the area under the curve (AUC), sensitivity, and specificity were calculated. Results:(1) Surgical situations and follow-up. All 88 patients underwent radical gastrectomy for gastric cancer and were diagnosed with advanced gastric adenocarcinoma through postoperative pathological examination. All 88 patients were followed up after surgery for 41(range, 36?48)months, with a 3-year overall survival rate of 69.32%. (2) Analysis of factors affecting the prognosis of advanced gastric adenocarcinoma after radical surgery. Results of multivariate analysis showed that preoperative carcinoembryonic antigen (CEA) and extramural venous invasion (EMVI) were independent factors affecting the prognosis of advanced gastric adenocarcinoma after radical surgery ( odds ratio=1.10, 7.72, 95% confidence interval as 1.01?3.82, 1.42?15.42, P<0.05). (3) Construction and evaluation of predictive model. The AUC of predictive efficacy of prognosis for advanced gastric adenocarcinoma of preoperative CEA and EMVI were 0.90 (95% confidence interval as 0.82?0.97) and 0.80 (95% confidence intervalas 0.71?0.89), respectively, with sensitivity of 85.25% and 78.69% and specificity of 100.00% and 81.48%, respec-tively. A predictive model was constructed by combining preoperative CEA and EMVI based on the results of multivariate analysis, and the AUC of the predictive model was 0.93 (95% confidence interval as 0.87?0.98), with sensitivity and specificity of 86.89% and 96.30%. Conclusions:CEA and EMVI are independent factors affecting the prognosis of advanced gastric adenocarcinoma after radical surgery. The predictive model constructed by combining preoperative CEA and EMVI has good predictive efficacy for patient prognosis.