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Acute myocardial infarction (AMI) has become a major cause of hospitalization and mortality in China. There has been limited data to date available to characterize AMI presentation, contemporary patterns of medical care, and outcomes in China. The CAMI Registry is a national project with the objectives to timely obtain real-world knowledge about AMI patients and to provide the platform for clinical research, guide preventive measures and care quality improvement efforts in China. The CAMI registry is a prospective, nationwide, multicenter observational study for AMI patients. The registry includes three levels of hospitals (representing typical Chinese governmental and administrative models) from all provinces and municipalities throughout Mainland China except Hong Kong and Macau. Sites were instructed to enroll consecutive patients with a primary diagnosis of AMI. Clinical data, treatments, outcomes and cost are collected by local investigators and captured electronically, with a standardized set of variables and standard definitions, and rigorous data quality control. Post-discharge patient follow-up to 2 years is planned. The CAMI Registry was launched in January 2013. A total of 108 hospitals have participated in the registry so far. As of September 2014, 26,103 patients with AMI were registered. The CAMI registry represents a well-supported and the largest national long-term registry-research-education platform for surveillance, research, prevention and care improvement for AMI in China, the world's most populous nation. The broad representation of all provinces and different-level hospitals will allow for the exploration of AMI across diverse geographic regions and economic circumstances.

Only a few randomized trials have analyzed the clinical outcomes of elderly ST-segment elevation myocardial infarction (STEMI) patients (≥ 75 years old). Therefore, the best reperfusion strategy has not been well established. An observational study focused on clinical outcomes was performed in this population. Based on the national registry on STEMI patients, the in-hospital outcomes of elderly patients with different reperfusion strategies were compared. The primary endpoint was defined as death. Secondary endpoints included recurrent myocardial infarction, ischemia driven revascularization, myocardial infarction related complications, and major bleeding. Multivariable regression analysis was performed to adjust for the baseline disparities between the groups. Patients who had primary percutaneous coronary intervention (PCI) or fibrinolysis were relatively younger. They came to hospital earlier, and had lower risk of death compared with patients who had no reperfusion. The guideline recommended medications were more frequently used in patients with primary PCI during the hospitalization and at discharge. The rates of death were 7.7%, 15.0%, and 19.9% respectively, with primary PCI, fibrinolysis, and no reperfusion (P < 0.001). Patients having primary PCI also had lower rates of heart failure, mechanical complications, and cardiac arrest compared with fibrinolysis and no reperfusion (P < 0.05). The rates of hemorrhage stroke (0.3%, 0.6%, and 0.1%) and other major bleeding (3.0%, 5.0%, and 3.1%) were similar in the primary PCI, fibrinolysis, and no reperfusion group (P > 0.05). In the multivariable regression analysis, primary PCI outweighs no reperfusion in predicting the in-hospital death in patients ≥ 75 years old. However, fibrinolysis does not. Early reperfusion, especially primary PCI was safe and effective with absolute reduction of mortality compared with no reperfusion. However, certain randomized trials were encouraged to support the conclusion.

There is a rapid growing demand for highly sensitive, easy adaptive and low-cost pressure sensing solutions in the fields of health monitoring, wearable electronics and home care. Here, we report a novel flexible inductive pressure sensor array with ultrahigh sensitivity and a simple construction, for large-area contact pressure measurements. In general, the device consists of three layers: a planar spiral inductor layer and ferrite film units attached on a polyethylene terephthalate (PET) membrane, which are separated by an array of elastic pillars. Importantly, by introducing the ferrite film with an excellent magnetic permeability, the effective permeability around the inductor is greatly influenced by the separation distance between the inductor and the ferrite film. As a result, the value of the inductance changes largely as the separation distance varies as an external load applies. Our device has achieved an ultrahigh sensitivity of 1.60 kPa−1 with a resolution of 13.61 Pa in the pressure range of 0–0.18 kPa, which is comparable to the current state-of-the-art flexible pressure sensors. More remarkably, our device shows an outstanding stability when exposed to environmental interferences, e.g., electrical noises from skin surfaces (within 0.08% variations) and a constant pressure load for more than 32 h (within 0.3% variations). In addition, the device exhibits a fast response time of 111 ms and a good repeatability under cyclic pressures varying from 38.45 to 177.82 Pa. To demonstrate its practical usage, we have successfully developed a 4 × 4 inductive pressure sensor array into a wearable keyboard for a smart electronic calendar application.

ADME genes are a set of genes which are involved in drug absorption, distribution, metabolism, and excretion (ADME). However, prognostic value and function of ADME genes in head and neck squamous cell carcinoma (HNSCC) remain largely unclear. In this study, we established an ADME-related prognostic model through the least absolute shrinkage and selection operator (LASSO) analysis in the Cancer Genome Atla (TCGA) training cohort and its robustness was validated by TCGA internal validation cohort and a Gene Expression Omnibus (GEO) external cohort. The 14-gene signature stratified patients into high- or low-risk groups. Patients with high-risk scores exhibited significantly poorer overall survival (OS) and disease-free survival (DFS) than those with low-risk scores. Receiver operating characteristic (ROC) curve analysis was used to confirm the signature’s predictive efficacy for OS and DFS. Furthermore, gene ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses showed that immune-related functions and pathways were enriched, such as lymphocyte activation, leukocyte cell-cell adhesion and T-helper cell differentiation. The Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) and other analyses revealed that immune cell (especially B cell and T cell) infiltration levels were significantly higher in the low-risk group. Moreover, patients with low-risk scores were significantly associated with immunotherapy and chemotherapy treatment benefit. In conclusion, we constructed a novel ADME-related prognostic and therapeutic biomarker associated with immune cell infiltration of HNSCC patients.

Nasopharyngeal carcinoma (NPC) is characterized by a high rate of local invasion and early distant metastasis. Increasing evidence indicates that epigenetic abnormalities play important roles in NPC development. However, the epigenetic mechanisms underlying NPC metastasis remain unclear. Here we investigate aberrantly methylated transcription factors in NPC tissues, and we identify the HOP homeobox HOPX as the most significantly hypermethylated gene. Consistently, we find that HOXP expression is downregulated in NPC tissues and NPC cell lines. Restoring HOPX expression suppresses metastasis and enhances chemosensitivity of NPC cells. These effects are mediated by HOPX-mediated epigenetic silencing of SNAIL transcription through the enhancement of histone H3K9 deacetylation in the SNAIL promoter. Moreover, we find that patients with high methylation levels of HOPX exhibit poor clinical outcomes in both the training and validation cohorts. In summary, HOPX acts as a tumour suppressor via the epigenetic regulation of SNAIL transcription, which provides a novel prognostic biomarker for NPC metastasis and therapeutic target for NPC treatment. HOPX is a transcription factor epigenetically silenced in several cancers. Here the authors, by analysing methylation profiles, identify HOPX as a suppressor of metastasis in nasopharyngeal carcinoma: mechanistically HOPX inhibits SNAIL transcription through deacetylation-mediated silencing.

The therapeutic strategy for advanced nasopharyngeal carcinoma (NPC) is still challenging. It is an urgent need to uncover novel treatment targets for NPC. Therefore, understanding the mechanisms underlying NPC tumorigenesis and progression is essential for the development of new therapeutic strategies. Here, we showed that TP53-regulated inhibitor of apoptosis (TRIAP1) was aberrantly overexpressed and associated with poor survival in NPC patients. TRIAP1 overexpression promoted NPC cell proliferation and suppressed cell death in vitro and in vivo, whereas TRIAP1 knockdown inhibited cell tumorigenesis and enhanced apoptosis through the induction of mitochondrial fragmentation, membrane potential alteration and release of cytochrome c from mitochondria into the cytosol. Intersecting with our previous miRNA data and available bioinformatic algorithms, miR-320b was identified and validated as a negative regulator of TRIAP1. Further studies showed that overexpression of miR-320b suppressed NPC cell proliferation and enhanced mitochondrial fragmentation and apoptosis both in vitro and in vivo, while silencing of miR-320b promoted tumor growth and suppressed apoptosis. Additionally, TRIAP1 restoration abrogated the proliferation inhibition and apoptosis induced by miR-320b. Moreover, the loss of miR-320b expression was inversely correlated with TRIAP1 overexpression in NPC patients. This newly identified miR-320b/TRIAP1 pathway provides insights into the mechanisms leading to NPC tumorigenesis and unfavorable clinical outcomes, which may represent prognostic markers and potential therapeutic targets for NPC treatment.

Background Although metabolic syndrome (MetS) is associated with an increased risk of various cancers, the combined impact of MetS and healthy lifestyle factors (HLF) on cancer risk is unclear. This study aimed to investigate the independent and combined effects of MetS and HLF on the risk of 16 site-specific cancers in a large community-based cohort. Methods A total of 289,557 participants in the UK Biobank were analyzed. MetS was defined using a combination of metabolic factors, while HLF scores were evaluated based on lifestyle behaviors, such as smoking, alcohol consumption, physical activity, and diet. Cox proportional hazard models were used to investigate the relationship between MetS or HLF and cancer risk, adjusting for age, sex, ethnicity, education level, family history of cancer, and the Townsend Deprivation Index (TDI). Results During a median follow-up of 11.69 years, 11,190 individuals developed cancer. MetS was associated with an increased risk of 9 cancers in men and 7 cancers in women. Compared with participants with unfavorable lifestyles, regardless of metabolic status, HLF was significantly associated with decreased risk of overall cancer (without MetS: HR: 0.812; 95% CI: 0.745–0.886 for intermediate lifestyle and HR: 0.757; 95% CI: 0.669–0.855 for favorable lifestyle; with MetS: HR: 0.702; 95% CI: 0.572–0.862 for favorable lifestyle) and oesophagus, stomach, liver, lung, bronchus, trachea cancers in men and of lung, bronchus, trachea cancers in women. Our analysis demonstrated that the protective association between HLF and reduced cancer risk was confined to subgroups without MetS. Specifically, this association was observed for cancers of the lip, oral cavity, pharynx, colon, rectum, pancreas, kidney, bladder, and lymphoid leukemia in men, and for overall cancer in women(HR: 0.917; 95% CI: 0.862–0.975 for intermediate lifestyle and HR: 0.875; 95% CI: 0.817–0.938 for favorable lifestyle). Conclusion MetS elevates risks for multiple cancers, while adopting a healthy lifestyle reduces risks of oesophagus, stomach, and lung, bronchus, trachea cancers in men and lung, bronchus, trachea cancer in women, regardless of metabolic status. However, MetS counteracts lifestyle-mediated protection against specific cancers—including lip, oral cavity, pharynx, colon, rectum, pancreas, kidney, and bladder cancers in men, as well as pancreas and breast cancers in women. These findings underscore the necessity to develop metabolic status-stratified management strategies and implement proactive prevention of MetS.

HER2, encoded by the ERBB2 gene, is a receptor tyrosine kinase frequently activated in human cancers via gene amplification, mutation, and/or protein overexpression. In an analysis of 42,415 prospectively analyzed solid tumors, we show that 14.5% of urothelial cancers (n = 295/2,035) have oncogenic or likely oncogenic ERBB2 alterations (6.7% ERBB2 mutation, 6.3% amplification of wildtype ERBB2 , and 1.5% concurrent mutation and amplification). Discordance of ERBB2 mutational status between primary and metastatic disease sites is common in patients with urothelial cancer as is discordance of ERBB2 mutational status between patient-derived organoid/xenograft models and the tumors from which they were derived. In patient-derived urothelial cancer models, the HER2-targeted antibody-drug conjugate (ADC) trastuzumab deruxtecan is significantly more effective than the HER kinase inhibitor neratinib. In a real-world cohort of patients with urothelial cancer treated with trastuzumab deruxtecan, co-mutation and amplification of ERBB2 is associated with exceptional clinical response. Our data support expanded clinical trials of HER2-targeted ADCs for urothelial cancers with low HER2 expression, the clinical testing of HER2 ADCs with alternative cytotoxic payloads, and the development of functional precision oncology platforms capable of assessing payload sensitivity pre-treatment as a guide to individualized therapy selection. Trastuzumab deruxtecan (T-DXd) is a HER2-targeted antibody drug conjugate. Through integrated laboratory and clinical studies, the authors identify significant ERBB2 (the gene that encodes the HER2 protein) mutational heterogeneity in patients with urothelial cancer and co-mutation and amplification of ERBB2 as a potential biomarker of exceptional response to T-DXd.

Metabolic heterogeneity plays a central role in sustaining uncontrolled cancer cell proliferation and shaping the tumor microenvironment (TME), which significantly compromises the clinical outcomes and responses to therapy in head and neck squamous cell carcinoma (HNSCC) patients. This highlights the urgent need to delineate the intrinsic heterogeneity and biological roles of metabolic vulnerabilities to advance precision oncology. The metabolic heterogeneity of malignant cells was identified using single-cell RNA sequencing (scRNA-seq) profiles and validated through bulk transcriptomes. Serine–glycine-one-carbon (SGOC) metabolism was screened out to be responsible for the aggressive malignant properties and poor prognosis in HNSCC patients. A 4-SGOC gene prognostic signature, constructed by LASSO-COX regression analysis, demonstrated good predictive performance for overall survival and therapeutic responses. Patients in the low-risk group exhibited greater infiltration of exhausted CD8+ T cells, and demonstrated better clinical outcomes after receiving immunotherapy and chemotherapy. Conversely, high-risk patients exhibited characteristics of cold tumors, with enhanced IMPDH1-mediated purine biosynthesis, resulting in poor responses to current therapies. IMPDH1 emerged as a potential therapeutic metabolic target. Treatment with IMPDH inhibitors effectively suppressed HNSCC cell proliferation and metastasis and induced apoptosis in vitro and in vivo by triggering GTP-exhaustion nucleolar stress. Our findings underscore the metabolic vulnerabilities of HNSCC in facilitating accurate patient stratification and individualized precise metabolic-targeted treatment.

Systematic inflammatory response syndrome (SIRS) and the accompanying sepsis pose a huge threat to human health worldwide. Heparin is a part of the standard supportive care for the disease. However, the molecular mechanism is not fully understood yet, and the potential signaling pathways that play key roles have not yet been elucidated. In this paper, the main findings regarding the molecular mechanisms associated with the beneficial effects of heparin, including inhibiting HMGB-1-driven inflammation reactions, histone-induced toxicity, thrombo-inflammatory response control and the new emerging mechanisms are concluded. To set up the link between the preclinical research and the clinical effects, the outcomes of the clinical trials are summarized. Then, the structure and function relationship of heparin is discussed. By providing an updated analysis of the above results, the paper highlights the feasibility of heparin as a possible alternative for sepsis prophylaxis and therapy.