Triple-negative breast cancer (TNBC) represents an aggressive breast cancer subtype with poor prognosis and limited targeted treatment options. This investigation examined the anti-cancer potential of Caerulomycin A (Cae A), a natural compound derived from marine actinomycetes, against TNBC. Cae A demonstrated selective inhibition of viability and proliferation in TNBC cell lines, including 4T1, MDA-MB-231, and MDA-MB-468, through apoptosis induction. Mechanistic analyses revealed that the compound induced sustained endoplasmic reticulum (ER) stress and subsequent upregulation of C/EBP homologous protein (CHOP) expression, resulting in mitochondrial damage-mediated apoptosis. Inhibition of ER stress or CHOP expression knockdown reversed mitochondrial damage and apoptosis, highlighting the essential role of ER stress and CHOP in Cae A's anti-tumor mechanism. Both oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) decreased in TNBC cells following Cae A treatment, indicating reduced mitochondrial respiratory and glycolytic capacities. This diminished energy metabolism potentially triggers ER stress and subsequent apoptosis. Furthermore, Cae A exhibited significant anti-tumor effects in the 4T1 tumor model in vivo without apparent toxicity. The compound also effectively inhibited human TNBC organoid growth. These results indicate that Cae A may serve as a potential therapeutic agent for TNBC, with its efficacy likely mediated through the disruption of glucose metabolism and the induction of ER stress-associated apoptosis.
Humans ; Endoplasmic Reticulum Stress/drug effects* ; Triple Negative Breast Neoplasms/genetics* ; Apoptosis/drug effects* ; Cell Line, Tumor ; Female ; Animals ; Glucose/metabolism* ; Mice ; Cell Proliferation/drug effects* ; Transcription Factor CHOP/genetics* ; Antineoplastic Agents/pharmacology* ; Mitochondria/metabolism* ; Mice, Inbred BALB C

Cerebral amyloid angiopathy(CAA)is one of the cerebral small vessel diseases in which amyloid-β is deposited in the cortical,subcortical and leptomeningal arterioles.The disease is commonly encountered in the elderly,characterized by recurrent lobar hemorrhage and cognitive dysfunction.In recent years,the diversity of intestinal microbiota and its products have been reported to be involved in the pathogenic process of central nervous system diseases through various pathways such as neuroinflammation and blood brain barrier leakage.However,the underlying mechanism of intestinal microbiota in CAA is not clear.It has been reported that intestinal microbiota disorder can induce intracranial Aβ production and aggregation,blood-brain barrier leakage,and Aβ transport receptor imbalance,and then damage in blood vessels,accompanied by neuroinflammatory mechanisms.The authors reviewed the potential mechanism of intestinal microbiota involved in amyloid deposition to provide a theoretical reference for the exploration of potential clinical therapeutic targets for CAA.

In order to explore the role of pre-basic course teaching in the standardized training of residents in clinical pathology, we have independently designed and constructed a pre-basic course teaching system mainly focusing on anatomy and histoembryology, consisting of two levels of theoretical teaching (small lectures by students and systematic lectures by instructors) and two dimensions of practical training (sample collection teaching and case teaching). This teaching model centering on participatory lecturing, practice, summarization, assessment, and feedback has been demonstrated effective. The results showed that the theoretical and practical assessment scores of the experimental group [(458.80±17.60) and (415.40±19.30), respectively] were significantly higher than those of the control group [(444.50±20.90) and (398.80±23.70), respectively]. Among 28 students of grades 2019 to 2021 surveyed for teaching effectiveness, 96.43% were satisfied with the teaching model. The established teaching model provides new ideas for the reform of teaching methods in the standardized training of residents in clinical pathology.

Background and purpose:Human epidermal growth factor receptor 2(HER2)is closely associated with drug efficacy and prognosis in urothelial carcinoma(UC).HER2 is a significant biomarker and therapeutic target in various tumors.In recent years,anti-HER2 antibody-drug conjugates have shown significant clinical efficacy in UC patients with HER2 overexpression.Therefore,an in-depth understanding of HER2 expression and its characteristics in Chinese UC patients is crucial to guide treatment decision-making,optimize treatment strategies and achieve personalized therapy.This study aimed to thoroughly investigate correlation of HER2 expression and clinicopathological characteristics in Chinese patients with UC.Methods:This study was a multicenter study that retrospectively included UC patients from urology departments of 8 tertiary hospitals in 5 geographical regions of China(North China,East China,South China,Central China and Northwest)whose tissue samples were collected from January 2023 to March 2024.Inclusion criteria:① age above 18 years;② UC diagnosed by histopathological or cytological examination;③ complete results of HER2 expression detection using immunohistochemistry(IHC)in the primary tumor site were required.Exclusion criteria:① diagnosed patients with tumors in other parts of the body;② physicians evaluated other situations that were not suitable for inclusion in this study.IHC results for HER2 expression and clinicopathological data were collected.HER2 expression was determined according to the criteria outlined in"Clinical pathological expert consensus on HER2 testing in urothelial carcinoma in China",with HER2 2+and 3+defined as HER2 overexpression.The HER2 expression and clinicopathological features were analyzed.This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(ethical number:2301268-12)and was registered at China Clinical Trial Registry(registration number:ChiCTR2300069746).Results:A total of 1054 patients with UC were included.Most of the tumors were bladder UC(n=807,76.6%).The mean age of patients was(66.8±10.5)years,and the majority were male(78.5%).The HER2 overexpression rate was 58.4%(n=616),with an additional 23%of patients having HER2 1+expression(n=242),and a small proportion exhibiting negative HER2 expression(n=196,18.6%).HER2 expression was significantly associated with various clinical and pathological characteristics such as Eastern Cooperative Oncology Group(ECOG)performance status,history of cardiovascular disease,history of metabolic disorders,smoking,UC disease location,differentiation grade,pathological type,and tumor stage.Conclusion:Retrospective analysis of multi-center data shows that HER2 expression is frequently observed in Chinese UC patients,with an overexpression rate of up to 58.4%.Furthermore,HER2 expression is closely associated with various clinical and pathological features of UC patients.This study underscores the critical importance of accurately assessing HER2 expression in UC patient to guide personalized therapies.

Pulmonary hypertension has a high mortality rate,and although targeted therapy is available,it is still incurable,and the long-term prognosis for patients is poor.As a tyrosine kinase inhibitor,imatinib was approved for marketing in China in 2002 for the treatment of chronic myelogenous leukemia and other tumor diseases.In addition to the antitumor effects,imatinib was found to improve hemodynamics and exercise tolerance in patients with severe pulmonary arterial hypertension,but the safety was suboptimal.With the emergence of new formulations of imatinib targeted at the lungs,it is expected to become a new targeted drug for pulmonary arterial hypertension.

Objective To analyze and integrate the best evidence of perioperative assessment and management in patients with chronic obstructive pulmonary disease(COPD).Methods Guideline websites,Chinese and English databases,related society websites were searched systematically to search and extract for guidelines,clinical decisions,recommended practice,evidence summaries,sys-tematic reviews and expert consensus on perioperative assessment and intervention in patients with COPD.The retrieval time was from the establishment of the database to January 31,2023.Results A total of 14 literatures were included:5 guidelines,3 expert consensus,3 clinical decisions,and 3 systematic reviews.Twenty-six pieces of evidence were collected from seven aspects,including gener-al principles,risk factors,nursing assessment,pulmonary rehabilitation nursing,airway manage-ment,effectiveness evaluation and shift management.Conclusion This study summarizes the best evidence of perioperative evaluation and intervention in patients with COPD,which can provide evi-dence-based evidence for perioperative management in patients with COPD.

Objective To investigate the correlation between TCM syndrome types and solar term of onset in patients with gastric cancer.Methods A total of 359 patients with gastric cancer admitted to the Cancer Center of the First Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2020 to August 2023 were included in this study,and the frequency distribution method was used to analyze their information such as sex,age,solar term of onset,differentiation,metastasis and TCM syndrome type.The solar term of onset corresponding to the onset date was calculated,and then the association between solar term of onset and TCM syndrome type in gastric cancer was analyzed.The circular distribution method was used to explore the peak of solar term of onset and TCM syndrome type.Results Among the 359 patients with gastric cancer included in this study,male patients were more than female patients(1.69∶1).The age of onset was mainly between 60 and 70 years old(117 cases,32.6%),and male patients(85 cases,72.6%)were more than female patients(32 cases,27.3%)in this age group.The most common TCM syndromes were qi and blood deficiency syndrome(160 cases,44.6%)and phlegm damp condensation syndrome(94 cases,26.2%).The onset of the disease mainly occurred in winter(132 cases,36.8%),and the peaks were light snow(31 cases,23.5%),major cold(25 cases,18.9%),heavy snow(23 cases,17.4%)and the start of winter(22 cases,16.7%).Qi and blood deficiency syndrome and phlegm damp condensation syndrome in patients with gastric cancer were correlated with solar terms and seasons(P<0.05).The 285 patients with gastric cancer were mainly poorly differentiated gastric cancer(175 cases,61.4%),mainly concentrated in winter(66 cases,37.7%).The main route of gastric cancer metastasis is lymph node metastasis,followed by liver and abdominal cavity metastasis.Conclusion Qi and blood deficiency syndrome and phlegm dampness condensation syndrome are common in patients with gastric cancer.The onset time of gastric cancer is mostly in winter,and the syndrome type is significantly correlated with the onset solar term and differentiation degree.

ObjectiveTo investigate the willingness of middle school students to engage in medicine and its influencing factors during COVID-19 pandemic in Lanzhou， so as to provide references for the early career planning education on middle school students. MethodsConvenient sampling method was used to choose 1 795 middle school students from 5 schools in Lanzhou from July 21 to July 31， 2022 for this study where an online questionnaire survey was distributed to collect data. A self-compiled questionnaire was used to gather the general information， assess the willingness to engage in medicine and seek the underlying reasons. The psychological resilience level of students was assessed using Resilience Scale for Adolescents. Then multivariate Logistic regression analysis was conducted to screen the factors associated with the willingness of middle school students to engage in medicine. ResultsAfter the local outbreak of COVID-19 in Lanzhou， 835 （46.52%） middle school students demonstrated their willingness to engage in medicine， and the top three reasons for their willingness were being affected by medical staff during the pandemic （75.69%）， having interests in medical sciences （67.31%）， and the potential increase of attention to national medical development after the epidemic （43.23%）. Logistical regression analysis showed that female gender （OR=1.438， P<0.01）， family members engaged in the medical and health industry （OR=1.574， P<0.01） and having a high psychological resilience score （OR=1.011， P<0.01） were related to the clear willingness to engage in medicine， while studying in senior middle school （OR=0.473， P<0.01） and excessive exposure （≥50%） to negative information during the epidemic （OR=0.797， P<0.05） were related to declining willingness to engage in medicine. ConclusionAfter the COVID-19 outbreak in Lanzhou， a large proportion of local middle school students show their willingness to engage in medicine， especially among those of female gender， having family members engaged in the medical and health industry and having high level of psychological resilience. Whereas students studying in senior middle school and with excessive exposure to negative information during the outbreak indicate low willingness to engage in medicine.

Aging poses a major risk factor for cardiovascular diseases, the leading cause of death in the aged population. However, the cell type-specific changes underlying cardiac aging are far from being clear. Here, we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age. We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profiles. Via transcription regulatory network analysis, we identified FOXP1, a core transcription factor in organ development, as a key downregulated factor in aged cardiomyocytes, concomitant with the dysregulation of FOXP1 target genes associated with heart function and cardiac diseases. Consistently, the deficiency of FOXP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes. Altogether, our findings depict the cellular and molecular landscape of ventricular aging at the single-cell resolution, and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.
Aged ; Animals ; Humans ; Aging/genetics* ; Forkhead Transcription Factors/metabolism* ; Myocytes, Cardiac/metabolism* ; Primates/metabolism* ; Repressor Proteins/metabolism* ; Transcriptome ; Macaca fascicularis/metabolism*

Objective To analyze and integrate the best evidence of perioperative assessment and management in patients with chronic obstructive pulmonary disease(COPD).Methods Guideline websites,Chinese and English databases,related society websites were searched systematically to search and extract for guidelines,clinical decisions,recommended practice,evidence summaries,sys-tematic reviews and expert consensus on perioperative assessment and intervention in patients with COPD.The retrieval time was from the establishment of the database to January 31,2023.Results A total of 14 literatures were included:5 guidelines,3 expert consensus,3 clinical decisions,and 3 systematic reviews.Twenty-six pieces of evidence were collected from seven aspects,including gener-al principles,risk factors,nursing assessment,pulmonary rehabilitation nursing,airway manage-ment,effectiveness evaluation and shift management.Conclusion This study summarizes the best evidence of perioperative evaluation and intervention in patients with COPD,which can provide evi-dence-based evidence for perioperative management in patients with COPD.