[Proactively embracing the challenges of multimorbidity].

With rapid socio-economic development and the acceleration of population aging, the average life span of human beings has increased significantly. Individuals suffering from the co-existence of multiple diseases (multimorbidity) have become a new normal in public health and posed severe challenge to human health. Multimorbidity significantly reduces the quality of life, increases disability and mortality risks, complicates disease treatment and care and increases burden of the healthcare system with higher costs. This commentary discusses the definition of multimorbidity and common public misconceptions, then assesses its profound impact on overall public health, socio-economic development and healthcare system. We also proposes the potential strategies to meet the challenges posed by multimorbidity. The main aim is to raise awareness of multimorbidity, advocate proactive responses to improve public health and build a healthy society through the development of prevention and treatment systems and promote precision prevention and treatment for multimorbidity.

[Research progress on global health competency and its models].

At present, the research on Global Health Competencies is mainly conducted in the field of the establishment of competency models and application of indicators. This review summarizes the research progress of the Global Health Competency and its models, and focuses on cutting-edge research from the aspects of target audience, purpose, content, classical model, methods and future development. The competency model is suggested to be adjusted and updated according to the practices of different countries and regions. The research and funding of the competency model in the field of public health is suggested to be strengthened, and the global health and diplomacy are suggested to be combined to enrich and improve the competency model. Finally, this review aims to promote Global Health Competencies research in China, especially to improve the global health talent training system and relevant policies in further research.

[Exploring implementation strategies for healthy longevity among the elderly population in China based on the delphi method].

Objective: To explore the implementation strategies for promoting healthy longevity among the elderly population in China based on the Delphi method. Methods: Through literature review and expert discussion, a framework for implementation strategies to achieve healthy longevity among the elderly was determined, and a preliminary checklist of implementation strategies was developed. The Delphi method was employed from August to December 2022, inviting 25 experts from various disciplines such as clinical medicine, public health, basic research, and the elderly care services industry. Experts were sent consultation questionnaires via email to assess the importance, feasibility, judgment basis and familiarity of each implementation strategy. Active coefficient, authority coefficient, and harmony coefficient were analyzed to ultimately determine the important and feasible implementation strategies for healthy longevity that were suitable for the Chinese elderly population. Results: The expert active coefficients of the two rounds were 96.00% (24/25) and 79.17% (19/24). The authority coefficients were (0.76±0.19) and (0.77±0.17). The average scores of importance were (4.32±0.84) and (4.36±0.82), and the corresponding scores of feasibility were (3.72±1.04) and (3.80±0.92). The harmony coefficients for the importance score were 0.269 (χ2=594.084, P<0.001) and 0.159 (χ2=193.624, P<0.001). The harmony coefficients for feasibility scores were 0.205 (χ2=452.008, P<0.001) and 0.167 (χ2=202.878, P<0.001). The final eight implementation strategies were identified after two rounds of consultation. Conclusion: Through two rounds of Delphi consultations, eight important and feasible implementation strategies for promoting healthy longevity that are suitable for the Chinese context have been proposed.

[Exploring a definition of healthy longevity in Chinese population based on Delphi method].

Objective: To explore a definition of healthy longevity in the Chinese population based on the Delphi method. Methods: Through a comprehensive literature review and expert consultation, the dimensions in the definition of healthy longevity were identified, and a preliminary list of questions was created. Experts in clinical medicine, public health, basic research, and the elderly care service industry, who had been working in the field of geriatric health for at least 5 years, were invited to participate in the Delphi survey from August to December 2022. The survey questionnaires were administered via email in two rounds, and experts were asked to select the optimal options from the provided questions. The active coefficients were expressed by the response rate, and a consensus was reached when the largest number of experts agreed for single-choice questions and more than 70% agreed for multiple-choice questions. Results: In the two rounds, the active coefficients were 96.00% (24/25) and 79.17% (19/24), respectively, and a consensus was finally reached on nine items, including age, physical health, common metabolic indicators, mental health, cognitive function, functional ability, social activity, self-rated health, and subjective well-being. Following discussions among the research team and experts, a final definition of healthy longevity was determined. Healthy longevity could refer to a state of good physical, psychological, cognitive function and social adaptation, as well as subjective well-being, in individuals aged 90 and above. Specifically, individuals with healthy longevity should be free from diseases associated with high disability rates and mortality, such as stroke, cancer, and Parkinson's disease. They should also maintain reasonable levels of common non-communicable disease indicators, such as blood pressure and blood glucose, and exhibit favorable mental health and cognitive function using validated measurement tools. In addition, individuals with healthy longevity should engage in social interactions with friends and relatives, care for family members, and go out to do things. Meanwhile, with the ability to complete the visual and hearing functions of daily life and communication, and the ability to complete basic activities such as walking, eating, bathing, toileting, dressing, continence of urination, and bowel movement independently, they could rate themselves to be in good health and experience a relatively high level of life satisfaction. Conclusion: A definition of healthy longevity in the Chinese population is established through the two-round Delphi consultation.

[Influencing factors of hypertension and diabetes care cascade: a qualitative study].

Objective: Employing the cascade care model, this qualitative study explores determinants influencing the cascading care stages of hypertension and diabetes by interviewing various stakeholders. Methods: In July 2023, purposive sampling was employed to recruit participants from Gongyi and Wugang cities in Henan Province, and Linqu County in Weifang City, Shandong Province. Semi-structured in-depth interviews were conducted with representatives of policymakers, healthcare institution managers, providers, and patients with hypertension and diabetes.And thematic analysis was performed using both inductive and deductive approaches. Results: A total of 82 individuals were interviewed, with an age range of (53.8±12.0) years, among which 48 (58.5%) were male; including 5 policymakers, 10 institutional managers, 20 healthcare providers, and 47 patients with hypertension and diabetes. The study identified both barriers and facilitating factors at the patient, healthcare provider, and system levels across various stages: awareness, screening, diagnosis, treatment, long-term management, and control of hypertension and diabetes. Conclusion: By delineating and analyzing the barriers and facilitators at each stage of hypertension and diabetes care, this study lays the groundwork for the development of effective, feasible, and sustainable implementation pathways, with significant implications for the enhanced management of hypertension and diabetes in China.

[Exploration of the classification of public health intervention and its implication for China].

Public health interventions refer to a series of organized and specific measures implemented in specific situations to achieve goals related to improving health, preventing and controlling diseases, and more. As research on intervention measures has deepened, the classification of public health interventions has gradually developed, clarifying the nature, categories and intervention targets of these measures. This typological study can help standardize the concepts of public health interventions, develop, select, and evaluate the effectiveness of intervention measures, and improve the effectiveness of public health actions. This paper reviews the main international classification models of intervention measures, analyzes and summarizes five classification methods of public health interventions, namely, based on goals, nature, objects, hierarchies, and modes of action, and introduces relevant cases. The paper proposes that China should conduct further in-depth and systematic research on public health interventions, develop evidence-based intervention measures and practices, promote the effective transformation of intervention measures and results, and facilitate the development of public health.

[Application progress of implementation research on diabetes management].

Diabetes is one of the most important non-communicable chronic diseases. Although a large amount of clinical evidence on the effectiveness of diabetes prevention and treatment interventions has been established, the current quality of care and results are still insufficient. Implementation Research can bridge the gap between research and practice. Implementation Research on diabetes management can clarify what is effective and what is ineffective in management, and promote the transformation of complex, multi-component interventions into medical practice faster and more effectively. This paper reviews the main research contents and application of implementation research of diabetes management at home and abroad, aiming to provide reference for related research and promote the application of implementation research in diabetes management in China.

[Recognition of abnormal changes in echocardiographic videos by an artificial intelligence assisted diagnosis model based on 3D CNN].

Objective: To investigate the diagnostic efficiency and clinical application value of an artificial intelligence-assisted diagnosis model based on a three-dimensional convolutional neural network (3D CNN) on echocardiographic videos of patients with hypertensive heart disease, chronic renal failure (CRF) and hypothyroidism with cardiac involvement. Methods: This study is a retrospective study. The patients with hypertensive heart disease, CRF and hypothyroidism with cardiac involvement, who admitted in Henan Provincial People's Hospital from April 2019 to October 2021, were enrolled. Patients were divided into hypertension group, CRF group, and hypothyroidism group. Additionally, a simple random sampling method was used to select control healthy individuals, who underwent physical examination at the same period. The echocardiographic video data of enrolled participants were analyzed. The video data in each group was divided into a training set and an independent testing set in a ratio of 5 to 1. The temporal and spatial characteristics of videos were extracted using an inflated 3D convolutional network (I3D). The artificial intelligence assisted diagnosis model was trained and tested. There was no case overlapped between the training and validation sets. A model was established according to cases or videos based on video data from 3 different views (single apical four chamber (A4C) view, single parasternal left ventricular long-axis (PLAX) view and all views). The statistical analysis of diagnostic performance was completed to calculate sensitivity, specificity and area under the ROC curve (AUC). The time required for the artificial intelligence and ultrasound physicians to process cases was compared. Results: A total of 730 subjects aged (41.9±12.7) years were enrolled, including 362 males (49.6%), and 17 703 videos were collected. There were 212 cases in the hypertensive group, 210 cases in the CRF group, 105 cases in the hypothyroidism group, and 203 cases in the normal control group. The diagnostic performance of the model predicted by cases based on single PLAX view and all views data was excellent: (1) in the hypertensive group, the sensitivity, specificity and AUC of models based on all views data were 97%, 89% and 0.93, respectively, while those of models based on a single PLAX view were 94%, 95%, and 0.94, respectively; (2) in the CRF group, the sensitivity, specificity and AUC of models based on all views data were 97%, 95% and 0.96, respectively, while those of models based on a single PLAX view were 97%, 89%, and 0.93, respectively; (3) in the hypothyroidism group, the sensitivity, specificity and AUC of models based on all views data were 64%, 100% and 0.82, respectively, while those of models based on a single PLAX view were 82%, 89%, and 0.86, respectively. The time required for the 3D CNN model to measure and analyze the echocardiographic videos of each subject was significantly shorter than that for the ultrasound physicians ((23.96±6.65)s vs. (958.25±266.17)s, P<0.001). Conclusions: The artificial intelligence assisted diagnosis model based on 3D CNN can extract the dynamic temporal and spatial characteristics of echocardiographic videos jointly, and quickly and efficiently identify hypertensive heart disease and cardiac changes caused by CRF and hypothyroidism.

[The prognostic effects of two comprehensive geriatric assessment methods in elderly patients with acute myeloid leukemia].

Objective: To evaluate the prognostic effects of two comprehensive geriatric assessment (CGA) methods in elderly patients with acute myeloid leukemia (AML). Methods: Ninety-seven patients with newly diagnosed AML at Beijing Hospital from August 2008 to December 2019 were included (≥60 years old). All patients were evaluated by two methods of CGA. One was IACA index proposed by Beijing Hospital, including instrumental activities of daily living (IADL), age, Charlson comorbidity index (CCI), albumin; the other was proposed by Italian FIL study group (FIL-CGA), including activities of daily living (ADL), IADL, age, and modified cumulative illness rating score for geriatrics (MCIRS-G). Results: Among 97 patients, 54 patients received standard chemotherapy, 16 with decitabine, 2 with targeted therapy and 25 with the best supportive therapy. The overall response rate (ORR) in 72 treated patients were 67.7%, 33.3% and 0 respectively in fit, unfit and frail groups according to IACA index (P=0.001). Based on FIL-CGA, the ORRs of fit, unfit and frail groups were 52.5%, 41.7% and 35.0% respectively (P=0.418). The 1-year OS rates of fit, unfit and frail groups regarding IACA method were 78.7%, 27.7% and 0 respectively (P<0.01). The 1-year OS rates of fit, unfit and frail groups regarding FIL-CGA method were 67.8%, 28.2% and 13.9% respectively (P<0.01), while no significant difference was seen between unfit group and frail group (P=0.111). The early death rates of fit, unfit and frail groups by IACA were 0, 6.0% and 28.6% respectively (P=0.006), while those by FIL-CGA were 2.3%, 5.9%, 13.9% respectively (P=0.123). Conclusion: Compared with FIL-CGA method, IACA predicts more effectively the treatment response, survival and early mortality in elderly patients with AML.

[Stress, anxiety, depression and insomnia in adults outside Hubei province during the COVID-19 pandemic].

Objective: To investigate the severity of stress, anxiety, depression and insomnia during the novel coronavirus disease (COVID-19) pandemic in adults outside Hubei Province, China. Methods: An online survey of psychological and sleep by using Questionnaire Star program from 5th to 19th February 2020 was conducted. The Impact of Event Scale-Revised was used to assess COVID-19 outbreak-related stress symptoms. Meanwhile, Questionnaires of Generalized Anxiety Disorder-7, Patient Health Questionnaire-9 and the Insomnia Severity Index were respectively used to assess the severity of anxiety, depression and insomnia symptoms prior to and during the COVID-19 pandemic. Results: A total of 3 134 subjects were included. Among the included subjects, 15.5% (487), 24.9% (779), 28.7% (899) and 30.9% (968) of the subjects had COVID-19-related stress symptoms, anxiety, depression and insomnia after the COVID-19 outbreak, respectively. The severity levels of anxiety, depression and insomnia were significantly increased during the COVID-19 pandemic compared to prior to the outbreak (all P<0.01). Furthermore, the subjects' stress response to the COVID-19 outbreak was an independent risk factor for increased anxiety, depression and insomnia after the outbreak. Conclusion: The COVID-19 outbreak resulted in related stress response and widespread increase in anxiety, depression, and insomnia outside Hubei Province, China in the general population. The aggravation of anxiety, depression and insomnia is associated with stress levels. Our data demonstrate that the widespread psychological and insomnia problems in the general population need to be addressed at the early phase of the pandemic.

[Fractional amplitude of low-frequency fluctuations in childhood and adolescence-onset schizophrenia: a resting state fMRI study].

Objective: To explore the whole brain activity features of childhood and adolescence-onset schizophrenia using resting state fMRI. Methods: A total of 63 childhood and adolescence-onset schizophrenia patients (patients group), admitted to the second affiliated hospital of Xinxiang Medical University from October 2013 to October 2015 and fulfilled our inclusion criteria, and 39 healthy controls with age, sex and education matched (control group) were enrolled, then a resting-state fMRI scan was conducted for each participant. Fractional amplitude of low-frequency fluctuations (fALFF) approach was used to explore the differences of resting-state brain function between patients and controls. Results: Compared with the healthy control group, patients group showed significantly decreased fALFF in left superior temporal gyrus and parietal lobe (MNI coordinate: x=-42, -57; y=-3, -21; z=-12, 9; voxels: 22, 32; t=-4.792 3, -5.269 7; Alphasim corrected, corrected P<0.05); patients group showed significantly increased fALFF in left frontal lobe and medial frontal gyrus, right superior frontal gyrus, Postcentral Gyrus, caudate, (MNI coordinate: x=-42, -21, 12, 27, 15; y=54, 39, 48, -18, 15; z=0, 21, 33, 30, 9; voxels: 12, 21, 17, 28, 18; t=4.784 8, 4.90 7, 4.861 5, 5.444 1, 4.270 4; Alphasim corrected, corrected P<0.05). When included age as a covariant, the analysis found that the brain region with significant fALFF change was the left thalamus with decreased fALFF (MNI coordinate: x=-6, y=-12, z=24; voxels: 9; t=-4.268 4; Alphasim corrected, corrected P<0.05) in patients group, while for other brain regions, there was no obvious change in the fALFF, compared with healthy group. Conclusion: Compared with control group, the results indicate that there are intrinsic brain activity abnormalities of some brain regions in childhood and adolescence-onset schizophrenia.

SNPs in Entire Mitochondrial Genome Sequences (≈15.4 kb) and cox1 Sequences (≈486 bp) Resolve Body and Head Lice From Doubly Infected People From Ethiopia, China, Nepal, and Iran But Not France.

Some people host lice on the clothing as well as the head. Whether body lice and head lice are distinct species or merely variants of the same species remains contentious. We sought to ascertain the extent to which lice from these different habitats might interbreed on doubly infected people by comparing their entire mitochondrial genome sequences. Toward this end, we analyzed two sets of published genetic data from double-infections of body lice and head lice: 1) entire mitochondrial coding regions (≈15.4 kb) from body lice and head lice from seven doubly infected people from Ethiopia, China, and France; and 2) part of the cox1 gene (≈486 bp) from body lice and head lice from a further nine doubly infected people from China, Nepal, and Iran. These mitochondrial data, from 65 lice, revealed extraordinary variation in the number of single nucleotide polymorphisms between the individual body lice and individual head lice of double-infections: from 1.096 kb of 15.4 kb (7.6%) to 2 bps of 15.4 kb (0.01%). We detected coinfections of lice of Clades A and C on the scalp hair of three of the eight people from Nepal: one person of the two people from Kathmandu and two of the six people from Pokhara. Lice of Clades A and B coinfected the scalp hair of one person from Atherton, Far North Queensland, Australia. These findings argue for additional large-scale studies of the body lice and head lice of double-infected people.

Second-generation sequencing of entire mitochondrial coding-regions (∼15.4 kb) holds promise for study of the phylogeny and taxonomy of human body lice and head lice.

The Illumina Hiseq platform was used to sequence the entire mitochondrial coding-regions of 20 body lice, Pediculus humanus Linnaeus, and head lice, P. capitis De Geer (Phthiraptera: Pediculidae), from eight towns and cities in five countries: Ethiopia, France, China, Australia and the U.S.A. These data (∼310 kb) were used to see how much more informative entire mitochondrial coding-region sequences were than partial mitochondrial coding-region sequences, and thus to guide the design of future studies of the phylogeny, origin, evolution and taxonomy of body lice and head lice. Phylogenies were compared from entire coding-region sequences (∼15.4 kb), entire cox1 (∼1.5 kb), partial cox1 (∼700 bp) and partial cytb (∼600 bp) sequences. On the one hand, phylogenies from entire mitochondrial coding-region sequences (∼15.4 kb) were much more informative than phylogenies from entire cox1 sequences (∼1.5 kb) and partial gene sequences (∼600 to ∼700 bp). For example, 19 branches had > 95% bootstrap support in our maximum likelihood tree from the entire mitochondrial coding-regions (∼15.4 kb) whereas the tree from 700 bp cox1 had only two branches with bootstrap support > 95%. Yet, by contrast, partial cytb (∼600 bp) and partial cox1 (∼486 bp) sequences were sufficient to genotype lice to Clade A, B or C. The sequences of the mitochondrial genomes of the P. humanus, P. capitis and P. schaeffi Fahrenholz studied are in NCBI GenBank under the accession numbers KC660761-800, KC685631-6330, KC241882-97, EU219988-95, HM241895-8 and JX080388-407.

Evidence for Ixodes holocyclus (Acarina: Ixodidae) as a vector for human lyme Borreliosis infection in Australia.

Ixodes holocyclus (Acarina: Ixodidae) and Ixodes cornuatus (Acarina: Ixodidae) are two tick species found in the more densely populated areas of Australia and are known to be the cause of the neurotoxic disease tick paralysis in humans and mammals. Borreliosis otherwise known as Lyme disease is an emerging infectious disease in humans in Australia. Borrelia burgdorferi sensu stricto (Spirochaetales: Spirochaetaceae) and sensu lato are closely related spirochetal species that are the causative agents of Lyme disease in humans. Clinical transmission of this tick-borne disease can be identified in several but not all cases by a characteristic rash known as erythema migrans. However, there has been no study of the tick vectors of this infection in Australia. We used morphological and molecular techniques to identify unequivocally the ticks on the patients of this study to be I. holocyclus and then show the presence of B. burgdorferi sensu stricto infection in erythema migrans biopsies. I. holocyclus has not previously been associated with erythema migrans or Lyme disease. Two patients presented to the lead author's medical practice with erythema migrans in mid and late 2012. The morphology and cytochrome oxidase 1 and ITS2 genes of the two ticks were studied. The skin at the attachment site was sampled by central biopsy for both real time and endpoint Borrelia polymerase chain reaction (PCR) analysis and subsequent sequencing. Morphologically, the two ticks were either I. holocyclus or I. cornuatus. Molecular studies and nucleotide sequencing revealed that both ticks were I. holocyclus. Real time and endpoint PCR on the central tissue biopsy samples returned positive results for B. burgdorferi DNA. Our results are evidence for transmission of B. burgdorferi sensu stricto species to humans by the tick I. holocyclus in Australia. I. holocyclus is commonly associated with human tick bites on virtually the entire eastern coastline of Australia.

Inactivation of putative PKS genes can double geldanamycin yield in Streptomyces hygroscopicus 17997.

The putative polyketide biosynthesis (PKS) genes cos10 and pg10 were inactivated by insertion of a kanamycin-resistance gene into the genome of the geldanamycin-producing strain, Streptomyces hygroscopicus 17997. The resultant inactivation were confirmed by PCR analysis. The abilities of the PKS gene inactivation strains to produce geldanamycin were compared with the natural geldanamycin- producing strain, S. hygroscopicus 17997. The cos10-inactivated strain exhibited an unchanged ability to produce geldanamycin, but the pg10- inactivated strain can produce twice the yield of the natural strain when grown under the same conditions. We propose that there is a sub-PKS pathway in the geldanamycin-producing strain, S. hygroscopicus 17997.

[Pachymic acid protects against Crohn's disease-like intestinal barrier injury and colitis in miceby suppressingintestinal epithelial cell apoptosis via inhibiting PI3K/AKT signaling].

OBJECTIVE: To investigate the effect of pachymic acid (PA) against TNBS-induced Crohn's disease (CD)-like colitis in mice and explore the possible mechanism. METHODS: Twenty-four C57BL/6J mice were randomized equally into control group, TNBS-induced colitis model group and PA treatment group. PA treatment was administered via intraperitoneal injection at the daily dose of 5 mg/kg for 7 days, and the mice in the control and model groups were treated with saline. After the treatments, the mice were euthanized for examination of the disease activity index (DAI) of colitis, body weight changes, colon length, intestinal inflammation, intestinal barrier function and apoptosis of intestinal epithelial cells, and the expressions of TNF-α, IL-6 and IL-1ß in the colonic mucosa were detected using ELISA. The possible treatment targets of PA in CD were predicted by network pharmacology. String platform and Cytoscape 3.7.2 software were used to construct the protein-protein interaction (PPI) network. David database was used to analyze the GO function and KEGG pathway; The phosphorylation of PI3K/AKT in the colonic mucosal was detected with Western blotting. RESULTS: PA significantly alleviated colitis in TNBS-treated mice as shown by improvements in the DAI, body weight loss, colon length, and histological inflammation score and lowered levels of TNF-α, IL-6 and IL-1ß. PA treatment also significantly improved FITC-dextran permeability, serum I-FABP level and colonic transepithelial electrical resistance, and inhibited apoptosis of the intestinal epithelial cells in TNBS-treated mice. A total of 248 intersection targets were identified between PA and CD, and the core targets included EGFR, HRAS, SRC, MMP9, STAT3, AKT1, CASP3, ALB, HSP90AA1 and HIF1A. GO and KEGG analysis showed that PA negatively regulated apoptosis in close relation with PI3K/AKT signaling. Molecular docking showed that PA had a strong binding ability with AKT1, ALB, EGFR, HSP90AA1, SRC and STAT3. In TNBS-treated mice, PA significantly decreased p-PI3K and p-AKT expressions in the colonic mucosa. CONCLUSION: PA ameliorates TNBS-induced intestinal barrier injury in mice by antagonizing apoptosis of intestinal epithelial cells possibly by inhibiting PI3K/AKT signaling.

Use of lung ultrasound for the diagnosis and treatment of pleural effusion.

Pleural effusion affects gas exchange, hemodynamic stability, and respiratory movement, thereby increasing the failure rate of intensive care unit discharge and mortality. Therefore, it is especially important to diagnose pleural effusion quickly to make the appropriate treatment decisions. The present review discusses the role of ultrasound in the diagnosis and puncture/drainage of pleural effusions and highlights the importance of lung ultrasound techniques in this patient population. We searched on PubMed, Embase, and Cochrane Library databases for articles from establishment to October 2022 using the following keywords: "lung ultrasound", "pulmonary ultrasound", "pleural effusion", "ultrasound-guided" and "thoracentesis". Lung ultrasound not only helps clinicians visualize pleural effusion but also to identify its different types and assess pleural effusion volume. It is also very important for thoracentesis, not only to increase safety and reduce life-threatening complications, but also to monitor the amount of fluid after drainage of pleural effusion. Lung ultrasound is a simple, noninvasive bedside technique with good sensitivity and specificity for the diagnosis and treatment of pleural effusions.

Breast cancer expression of YKL-40 correlates with tumour grade, poor differentiation, and other cancer markers.

BACKGROUND: Serum levels of a secreted glycoprotein YKL-40 are elevated in patients with a wide range of cancers including breast, colorectal, and ovarian cancers. Furthermore, these increased levels correlate with poorer survival of cancer patients, suggesting that serum levels of YKL-40 might be a prognostic biomarker. However, the tissue expression of YKL-40 and its relationship with clinical outcomes and other potential markers are poorly understood. METHODS: Tissue samples from invasive breast cancers, breast ductal carcinoma in situ (DCIS), and cancer-free reduction mammoplasty were enrolled. YKL-40 expression was measured using immunohistochemistry and evaluated by a semi-quantification assay. Statistical analyses explored the relationship of YKL-40 with clinical outcome and other breast cancer biomarkers. RESULTS: Breast ductal carcinoma in situ expressed low and moderate levels of YKL-40. In the subset of 203 patients with invasive cancer, YKL-40 levels were positively correlated with tumour grade (P<0.0001) and Her2/neu (P<0.01), but negatively correlated with oestrogen (P<0.0001) and progesterone receptor (P<0.0001). YKL-40 levels were inversely correlated with expressions of GATA3 (P=0.0137) and E-cadherin (P=0.0417). CONCLUSION: These data demonstrate that expression levels of YKL-40 are associated with tumour grade, poor differentiation, and other breast cancer markers, highlighting that tissue levels of YKL-40 serve as a valuable biomarker for breast cancer diagnosis and prognosis.

The ets protein PEA3 suppresses HER-2/neu overexpression and inhibits tumorigenesis.

Because HER-2/neu overexpression is important in cancer development, we looked for a method of suppressing the cell transformation mediated by HER-2/neu overexpression. We have identified that the DNA-binding protein PEA3, which is encoded by a previously isolated gene of the ets family, specifically targeted a DNA sequence on the HER-2/neu promoter and downregulated the promoter activity. Expression of PEA3 resulted in preferential inhibition of cell growth and tumor development of HER-2/neu-overexpressing cancer cells. This is a new approach to targeting HER-2/neu overexpression and also provides a rationale to the design for repressors of diseases caused by overexpression of pathogenic genes.