Triple-negative breast cancer (TNBC) represents a distinctive subtype, characterized by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). Due to its high inter-tumor and intra-tumor heterogeneity, TNBC poses significant chanllenges for personalized diagnosis and treatment. The advant of clustered regular interspaced short palindromic repeats (CRISPR) technology has profoundly enhanced our understanding of the structure and function of the TNBC genome, providing a powerful tool for investigating the occurrence and development of diseases. This review focuses on the application of CRISPR/Cas technology in the personalized diagnosis and treatment of TNBC. We begin by discussing the unique attributes of TNBC and the limitations of current diagnostic and treatment approaches: conventional diagnostic methods provide limited insights into TNBC, while traditional chemotherapy drugs are often associated with low efficacy and severe side effects. The CRISPR/Cas system, which activates Cas enzymes through complementary guide RNAs (gRNAs) to selectively degrade specific nucleic acids, has emerged as a robust tool for TNBC research. This technology enables precise gene editing, allowing for a deeper understanding of TNBC heterogeneity by marking and tracking diverse cell clones. Additionally, CRISPR facilitates high-throughput screening to promptly identify genes involved in TNBC growth, metastasis, and drug resistance, thus revealing new therapeutic targets and strategies. In TNBC diagnostics, CRISPR/Cas was applied to develop molecular diagnostic systems based on Cas9, Cas12, and Cas13, each employing distinct detection principles. These systems can sensitively and specifically detect a variety of TNBC biomarkers, including cell-specific DNA/RNA and circulating tumor DNA (ctDNA). In the realm of precision therapy, CRISPR/Cas has been utilized to identify key genes implicated in TNBC progression and treatment resistance. CRISPR-based screening has uncovered potential therapeutic targets, while its gene-editing capabilities have facilitated the development of combination therapies with traditional chemotherapy drugs, enhancing their efficacy. Despite its promise, the clinical translation of CRISPR/Cas technology remains in its early stages. Several clinical trials are underway to assess its safety and efficacy in the treatment of various genetic diseases and cancers. Challenges such as off-target effects, editing efficiency, and delivery methods remain to be addressed. The integration of CRISPR/Cas with other technologies, such as 3D cell culture systems, human induced pluripotent stem cells (hiPSCs), and artificial intelligence (AI), is expected to further advance precision medicine for TNBC. These technological convergences can offer deeper insights into disease mechanisms and facilitate the development of personalized treatment strategies. In conclusion, the CRISPR/Cas system holds immense potential in the precise diagnosis and treatment of TNBC. As the technology progresses and becomes more costs-effective, its clinical relevance will grow, and the translation of CRISPR/Cas system data into clinical applications will pave the way for optimal diagnosis and treatment strategies for TNBC patients. However, technical hurdles and ethical considerations require ongoing research and regulation to ensure safety and efficacy.

The European Society of Cardiology (ESC) released the "2024 ESC guidelines for the management of elevated blood pressure and hypertension" on August 30, 2024. This guideline updates the 2018 "Guidelines for the management of arterial hypertension." One notable update is the introduction of the concept of "elevated blood pressure" (120-139/70-89 mm Hg). Additionally, a new systolic blood pressure target range of 120-129 mm Hg has been proposed for most patients receiving antihypertensive treatment. The guideline also includes numerous additions or revisions in areas such as non-pharmacological interventions and device-based treatments for hypertension. This article interprets the guideline's recommendations on definition and classification of elevated blood pressure and hypertension, and cardiovascular disease risk assessment, diagnosing hypertension and investigating underlying causes, preventing and treating elevated blood pressure and hypertension. We provide a comparison interpretation with the 2018 "Guidelines for the management of arterial hypertension" and the "2017 ACC/AHA guideline on the prevention, detection, evaluation, and management of high blood pressure in adults."

An electrochemical chemical oxygen demand(COD)sensor was proposed based on a FTO/TiO2/PbO2 electrode and a thin-layer electrochemical cell.The FTO/TiO2/PbO2 electrode was characterized by X-ray photoelectronic spectroscopy(XPS),X-ray diffraction(XRD)spectroscopy and electrochemical technique,and the results indicated that the rapid decrease in the output signals of the electrochemical COD sensor could be attributed to oxidation of PbSO4 occurring on the surface of FTO/TiO2/PbO2 electrode.The PbO2 deposition time and concentration of Na2SO4 were further optimized and then the electrochemical COD sensor was challenged by real samples including laker water sample,river water sample and wastewater sample.The evolution trend of signals of the electrochemical COD sensor in response to lake and river water samples was identical with that obtained with the standard method(HJ/T399-2007,Water quality-determination of the chemical oxygen demand-fast digestion-spectrophotometric method).The electrochemical COD sensor exhibited significant increase in the signal intensity after the samples were switched from lake water to wastewater sample,and a mean value of 32.5 mg/L with relative standard deviation(RSD)of 6.8%were obtained after measuring 45 times the wastewater with COD value of 30 mg/L under a sampling interval of 400 s.The as-prepared electrochemical COD sensor possessed good promise in regular monitoring of COD,discharge of wastewater and industrial process control,with advantages such as a small sampling interval,mild reaction conditions and no requirement of toxic and harmful chemical reagents.

Objective:To evaluate inflammation early in the infarct zone and its dynamic changes after acute myocardial infarction (AMI) using 18F-FDG PET imaging, and analyze its relationship with left ventricular remodeling progression (LVRP). Methods:Sixteen Bama miniature pigs (4-6 months old, 8 females) were selected. AMI models were established by balloon occlusion of the left anterior descending artery. 18F-FDG PET imaging was performed before AMI and at days 1, 5, 8, and 14 post-AMI to evaluate the regional inflammation response. 18F-FDG SUV ratio (SUVR) and the percentage of uptake area of left ventricle (F-extent) in the infarct zone, and the SUVRs of the spleen and bone marrow, were measured. Echocardiography and 99Tc m-methoxyisobutylisonitrile(MIBI) SPECT myocardial perfusion imaging (MPI) were performed at the above time points and on day 28 post-AMI to assess left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and myocardial perfusion defect extent. The degree of LVRP at day 28 post-AMI was defined as ΔLVESV(%)=(LVESV AMI 28 d-LVESV AMI 1 d)/LVESV AMI 1 d×100%. Data were analyzed using repeated measures analysis of variance, Kruskal-Wallis rank sum test and Pearson correlation analysis. Results:Twelve pigs were successfully modeled and completed the study. Inflammation in the infarct zone persisted until day 14 post-AMI. The SUVR of the infarct zone pre-AMI and at days 1, 5, 8, and 14 post-AMI were 1.03±0.08, 3.49±1.06, 2.93±0.90, 2.38±0.76, and 1.63±0.62, respectively ( F=49.31, P<0.001). The F-extent values in the infarct zone pre-AMI and at days 1, 5, 8, and 14 post-AMI were 0, (40.08±12.46)%, (40.00±12.76)%, (31.08±12.82)%, and 16.50%(7.25%, 22.00%), respectively ( H=37.61, P=0.001). There were no significant differences in the SUVRs of bone marrow and spleen before and after AMI ( F values: 0.69 and 0.77, both P>0.05). At day 1 post-AMI, both SUVR and F-extent in the infarct zone were significantly correlated with LVRP ( r values: 0.82 and 0.70, P values: 0.001 and 0.035). Conclusions:18F-FDG PET imaging can be used to evaluate inflammation in the infarct area and its dynamic changes after AMI. Inflammation in the infarct area is severe at day 1, and then gradually decreases. The extent and severity of inflammation visible on 18F-FDG PET imaging 1 d after AMI are closely related to LVRP.

Artificial vascular graft(AVG)fistula is widely used for hemodialysis treatment in patients with renal failure.However,it has poor elasticity and compliance,leading to stenosis and thrombosis.The ideal artificial blood vessel for dialysis should replicate the structure and components of a real artery,which is primarily maintained by collagen in the extracellular matrix(ECM)of arterial cells.Studies have revealed that in hepatitis B virus(HBV)-induced liver fibrosis,hepatic stellate cells(HSCs)become hyperactive and produce excessive ECM fibers.Furthermore,mechanical stimulation can encourage ECM secretion and remodeling of a fiber structure.Based on the above factors,we transfected HSCs with the hepatitis B viral X(HBX)gene for simulating the process of HBV infection.Subsequently,these HBX-HSCs were implanted into a polycaprolactone-polyurethane(PCL-PU)bilayer scaffold in which the inner layer is dense and the outer layer consists of pores,which was mechanically stimulated to promote the secretion of collagen nanofiber from the HBX-HSCs and to facilitate crosslinking with the scaffold.We obtained an ECM-PCL-PU composite bionic blood vessel that could act as access for dialysis after decellularization.Then,the vessel scaffold was implanted into a rabbit's neck arteriovenous fistula model.It exhibited strong tensile strength and smooth blood flow and formed autologous blood vessels in the rabbit's body.Our study demonstrates the use of human cells to create biomimetic dialysis blood vessels,providing a novel approach for creating clinical vascular access for dialysis.

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.

HDAC(histone deacetylase)is a class of epigenetic modifying enzymes that can deacetylate proteins by altering the acetylation status of histones in the nucleus,regulating promoter activation levels,and thereby affecting downstream gene expression.However,expression changes of HDACs during endo-thelial differentiation are still unclear.This study used a three-stage method to induce human induced pluripotent stem cells(hiPSCs)to differentiate into endothelial cells,and qRT-PCR was used to detect the expression changes of class I HDAC(HDAC1,2)and class Ⅱ HDAC(HDAC4,5)genes.It was found that HDAC5 exhibits significant expression changes during endothelial differentiation.It is downreg-ulated by 90％during the mesodermal differentiation stage(P＜0.01),upregulated by 3.7-fold during the vascular precursor stage(P＜0.01),and subsequently downregulated by 70％during the late stage of endothelial differentiation(P＜0.01).Immunoblotting experiments further confirmed that HDAC5 under-goes periodic expression changes during endothelial differentiation.Mechanistic studies have shown that HDAC5 downregulation during the differentiation stage of the mesoderm is mediated by Wnt signaling.CHIR99021 treatment and overexpression of Wnt3a can activate the Wnt signaling pathway,leading to HDAC5 downregulation.Inhibiting the Wnt signaling pathway through IWP-2 promotes the recovery of HDAC5 expression.In addition,it was found that HDAC5 is mainly localized in the nucleus,and IWP-2 restores HDAC5 expression,but it remains in the cytoplasm.Further research suggests that downregu-lation of HDAC5 during mesodermal differentiation may contribute to the expression of the mesodermal marker BraT.Treatment with the HDAC inhibitor BML210 can promote early mesodermal differentiation,interfere with endothelial differentiation of vascular precursor cells,and enhance late-stage endothelial differentiation.In conclusion,HDAC5 displays a stage-specific expression during endothelial differentia-tion,and Wnt signaling activation is the main mechanism regulating the downregulation of HDAC5 during the mesoderm stage.

Aim To observe the effect of Astragalus membranaceus and Angelica sinensis on the apoptosis of chondrocytes,and to investigate the effect of Astrag-alus membranaceus and Angelica sinensis on the sur-vival of fresh ostecartilage allograft.Methods Forty-eight 4-month-old New Zealand white rabbits,half male and half female,were randomly divided into sham operation group,model group,positive group and As-tragalus and Angelica 5∶1 group.In addition to the sham operation group,the other groups were both male and female donors and recipients for knee joint osteo-cartilage cross transplantation modeling.After 8 weeks of drug intervention,samples were taken for general observation,HE staining,saffrane-O staining,immu-nohistochemical staining,qPCR and Western blot de-tection.Results Compared with model group,As-tragalus and Angelica 5∶1 group and positive group,the repair site healed better,the morphology of osteo-chondrocytes tended to be normal,and the division and proliferation were obvious.Proteoglycan deposition in-creased and type Ⅱ collagen content was higher,the differences were statistically significant(P＜0.05).qPCR and Western blot results showed that compared with model group,the mRNA and protein expressions of Bax,caspase-3 and caspase-9 in other groups were significantly decreased(P＜0.05).Conclusion As-tragalus and Angelica can promote the survival of fresh osteochondral allograft,and its mechanism may be re-lated to promoting collagen production,promoting chondrocyte proliferation and inhibiting chondrocyte apoptosis.

Objective To construct a risk prediction model by integrating the molecular subtypes of pan-creatic ductal adenocarcinoma(PDAC)and immune-related genes.Methods With GSE71729 data set(n=145)as the training set,the differentially expressed genes and differential immune-related genes between the squamous and non-squamous subtypes of PDAC were integrated to construct a regulatory network,on the basis of which five immune marker genes regulating the squamous subtype were screened out.An integrated immune score(IIS)model was constructed based on patient survival information and immune marker genes to predict the clinical prog-nosis of PDAC patients,and its predictive performance was tested with 5 validation sets(n=758).Results PDAC patients were assigned into high risk and low risk groups according to the IIS.In both training and validation sets,the overall survival of patients in the high risk group was shorter than that in the low risk group(both P＜0.001).The multivariable Cox regression showed that IIS was an independent prognostic factor for PDAC(HR=2.16,95％CI=1.50-3.10,P＜0.001).Conclusion IIS can be used for risk stratification of PDAC patients and may become a potential prognostic marker for PDAC.

Objective: To construct a prognostic model for unsuccessful removal of nasogastric tube (NGT) was the aim of our study. Methods: This study examined patients with swallowing disorders receiving NGT feeding due to stroke or traumatic brain injury in a regional hospital. Clinical data was collected, such as age, sex, body mass index (BMI), level of activities of daily living (ADLs) dependence. Additionally, gather information regarding the enhancement in Functional Oral Intake Scale (FOIS) levels and the increase in food types according to the International Dysphagia Diet Standardization Initiative (IDDSI) after one month of swallowing training. A stepwise logistic regression analysis model was employed to predict NGT removal failure using these parameters. Results: Out of 203 patients, 53 patients (26.1%) had experienced a failed removal of NGT after six months of follow-up. The strongest predictors for failed removal were age over 60 years, underweight BMI, total dependence in ADLs, and ischemic stroke. The admission prediction model categorized patients into high, moderate, and low-risk groups for removal failure. The failure rate of NGT removal was high not only in the high-risk group but also in the moderate-risk groups when there was no improvement in FOIS levels and IDDSI food types. Conclusion Our predictive model categorizes patients with brain insults into risk groups for swallowing disorders, enabling advanced interventions such as percutaneous endoscopic gastrostomy for high-risk patients struggling with NGT removal, while follow-up assessments using FOIS and IDDSI aid in guiding rehabilitation decisions for those at moderate risk.