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Objective To explore the effectiveness of Failure Modes and Effects Analysis(FMEA)in emergency man-agement of sudden incidents involving outpatient and emergency patients in general hospitals,to provide references for the optimi-zation of emergency response process for such incidents.Methods Based on FMEA,we identified and evaluated risks in the e-mergency response procedures for sudden incidents involving outpatient and emergency patients in general hospitals.Potential fail-ure modes were analyzed to identify key risks with a Risk Priority Number(RPN)greater than 125.Continuous quality improve-ment measures were implemented to control these risks,and the effectiveness of these controls was evaluated using chi-square tests for statistical analysis.Results A total of 16 risk points in 4 major areas were identified.After implementing continuous quality improvement measures,the RPNs of these high-risk points decreased to below 125,effectively controlling the potential risks.This intervention significantly improved the utilization rate of emergency equipment,the timely reporting rate of sudden in-cidents,the timely feedback rate of emergency response,with statistically significant differences(P＜0.01).Conclusion The application of FMEA to outpatient and emergency management of sudden incidents helps optimize the emergency response process,thus enhancing the emergency response capability of general hospitals and ensuring effective handling of such incidents.

Lung cancer is a major cause of cancer-related mortality worldwide. Among patients with non-small cell lung cancer (NSCLC), approximately 3%-7% harbor anaplastic lymphoma kinase (ALK) gene fusions. In recent years, multiple tyrosine kinase inhibitors (TKIs) have significantly improved the survival of patients with metastatic ALK-positive NSCLC. However, disease progression due to resistance remains a challenge. This article retrospectively analyzes a case of advanced lung adenocarcinoma with the echinoderm microtubule associated protein like 4 (EML4)-ALK fusion variant 3 (V3). The patient developed resistance to Lorlatinib treatment accompanied by mesenchymal-epithelial transition factor (MET) amplification. Effective tumor control was achieved with the combined use of Crizotinib and Lorlatinib, providing a valuable reference for further exploration of treatment strategies following resistance to ALK-TKIs in clinical practice.
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Humans ; Adenocarcinoma/genetics* ; Adenocarcinoma of Lung/genetics* ; Aminopyridines/therapeutic use* ; Crizotinib/therapeutic use* ; Drug Resistance, Neoplasm/drug effects* ; Lactams/therapeutic use* ; Lung Neoplasms/genetics* ; Oncogene Proteins, Fusion/metabolism* ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins c-met/metabolism* ; Pyrazoles/therapeutic use*

Breast cancer, the most common malignancy in the world, also causes the most death cases of women among malignancies. Breast cancer risk reduction guidelines (version 2023) was updated by National Comprehensive Cancer Network (NCCN). Based on high-level evidences from evidence-based medicine and the latest research progress, the guidelines provided standardized guidance for breast cancer risk assessment and risk reduction strategies for individuals without a history of invasive breast cancer or ductal carcinoma in situ, which has attracted widespread attention from clinicians worldwide. Breast cancer is also the most common malignancy in Chinese women, and the number of newly diagnosed breast cancer cases each year in China ranks first in the world due to the large population, so the breast cancer prevention has become a major public health challenge in China. Aimed to provide reference for breast cancer prevention in China, this article interpreted the guidelines (the new version) based on the characteristics of breast structure in Asian women and the epidemiological characteristics of breast cancer in China.

Cell membrane affinity chromatography has been widely applied in membrane protein (MP)-targeted drug screening and interaction analysis. However, in current methods, the MP sources are derived from cell lines or recombinant protein expression, which are time-consuming for cell culture or purification, and also difficult to ensure the purity and consistent orientation of MPs in the chromatographic stationary phase. In this study, a novel in situ synthesis membrane protein affinity chromatography (iSMAC) method was developed utilizing cell-free protein expression (CFE) and covalent immobilized affinity chromatography, which achieved efficient in situ synthesis and unidirectional insertion of MPs into liposomes in the stationary phase. The advantages of iSMAC are: 1) There is no need to culture cells or prepare recombinant proteins; 2) Specific and purified MPs with stable and controllable content can be obtained within 2 h; 3) MPs maintain the transmembrane structure and a consistent orientation in the chromatographic stationary phase; 4) The flexible and personalized construction of cDNAs makes it possible to analyze drug binding sites. iSMAC was successfully applied to screen PDGFRβ inhibitors from Salvia miltiorrhiza and Schisandra chinensis. Micro columns prepared by in-situ synthesis maintain satisfactory analysis activity within 72 h. Two new PDGFRβ inhibitors, salvianolic acid B and gomisin D, were screened out with K _D values of 13.44 and 7.39 μmol/L, respectively. In vitro experiments confirmed that the two compounds decreased α-SMA and collagen Ӏ mRNA levels raised by TGF-β in HSC-T6 cells through regulating the phosphorylation of p38, AKT and ERK. In vivo, Sal B could also attenuate CCl₄-induced liver fibrosis by downregulating PDGFRβ downstream related protein levels. The iSMAC method can be applied to other general MPs, and provides a practical approach for the rapid preparation of MP-immobilized or other biological solid-phase materials.

Astragali Radix(AR)is a clinically used herbal medicine with multiple immunomodulatory activities that can strengthen the activity and cytotoxicity of natural killer(NK)cells.However,owing to the complexity of its composition,the specific active ingredients in AR that act on NK cells are not clear yet.Cell membrane chromatography(CMC)is mainly used to screen the active ingredients in a complex system of herbal medicines.In this study,a new comprehensive two-dimensional(2D)NK-92MI CMC/C18 column/time-of-flight mass spectrometry(TOFMS)system was established to screen for potential NK cell acti-vators.To obtain a higher column efficiency,3-mercaptopropyltrimethoxysilane-modified silica was synthesized to prepare the NK-92MI CMC column.In total,nine components in AR were screened from this system,which could be washed out from the NK-92MI/CMC column after 10 min,and they showed good affinity for NK-92MI/CMC column.Two representative active compounds of AR,isoastragaloside Ⅰ and astragaloside Ⅳ,promoted the killing effect of NK cells on K562 cells in a dose-dependent manner.It can thus suggest that isoastragaloside Ⅰ and astragaloside Ⅳ are the main immunomodulatory compo-nents of AR.This comprehensive 2D NK-92MI CMC analytical system is a practical method for screening immune cell activators from other herbal medicines with immunomodulatory effects.

COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.

RAS, a member of the small GTPase family, functions as a binary switch by shifting between inactive GDP-loaded and active GTP-loaded state. RAS gain-of-function mutations are one of the leading causes in human oncogenesis, accounting for ∼19% of the global cancer burden. As a well-recognized target in malignancy, RAS has been intensively studied in the past decades. Despite the sustained efforts, many failures occurred in the earlier exploration and resulted in an 'undruggable' feature of RAS proteins. Phosphorylation at several residues has been recently determined as regulators for wild-type and mutated RAS proteins. Therefore, the development of RAS inhibitors directly targeting the RAS mutants or towards upstream regulatory kinases supplies a novel direction for tackling the anti-RAS difficulties. A better understanding of RAS phosphorylation can contribute to future therapeutic strategies. In this review, we comprehensively summarized the current advances in RAS phosphorylation and provided mechanistic insights into the signaling transduction of associated pathways. Importantly, the preclinical and clinical success in developing anti-RAS drugs targeting the upstream kinases and potential directions of harnessing allostery to target RAS phosphorylation sites were also discussed.

Objective　To investigate the relationship between the overall burden of cerebral small vessel disease (CSVD) and cognitive impairment in patients with atrial fibrillation (AF) associated stroke.Methods　Patients with acute cerebral infarction related to the cause of atrial fibrillation who were hospitalized in the Department of Neurology,Qingdao University Affiliated Hospital were collected from September 2018 to May 2020.According to the imaging findings of magnetic resonance imaging,the patients were divided into four groups:0,1,2,3~4.Seven days after the onset of stroke,the patients were assessed with the Montreal Cognitive Assessment Scale (MoCA).The patients were divided into cognitive impairment group and non-cognitive impairment group.A total of 168 patients completed the assessment.Results　Age,hypertension,smoking history,MOCA score,CHA2DS2-VASC score are related to total CSVD score.Cognitive impairment after atrial fibrillation-related stroke is related to total CSVD score,age,smoking history,drinking history,CHA2DS2-VASc score,frontal lobe and thalamic infarction.Cognitive domain impairment is mainly visual space,executive ability,linguistic ability and delayed recall ability.Conclusion　The severity of the overall burden of CSVD is related to cognitive impairment in patients with atrial fibrillation-related stroke.

Objective　To explore the relationship between the blood metabolic indexes and the occurrence and development of Alzheimer’s disease (AD) and to find the correlation with cerebrospinal fluid biomarkers.Methods　A total of 66 patients diagnosed with AD from September 2018 to July 2020 and 36 normal controls with no difference in age and gender were enrolled in this study.The levels of serum metabolic indexes were detected in all subjects.The levels of tau protein and amyloid protein (Aβ) in cerebrospinal fluid were measured and compared.and the correlation between tau protein and metabolic indexes was analyzed.Results　The levels of homocysteine (Hcy)，high density lipoprotein cholesterol (HDL-C)，folic acid and Vitamin B12 (VitB12) in AD group were significantly different from those in control group (P<0.05);after adjustment of multivariate regression analysis.HDL-C and VitB12 were significantly correlated with the occurrence of AD;the levels of HCY,HDL-C.folic acid and VitB12 were significantly correlated with cognitive score in Pearson correlation analysis (P<0.05).The level of tau protein in cerebrospinal fluid was significantly higher than that in the control group.and the concentration of Aβ42 was significantly lower than that in the control group.Pearson correlation analysis showed that HDL-C was positively correlated with tau protein level.and VitB12 was positively correlated with Aβ42 (P<0.05).Conclusion　This study shows that the degree of cognitive impairment in AD patients is positively correlated with HCY and HDL-C levels.and the levels of folic acid and VitB12 are negatively correlated with the severity of cognitive impairment in AD patients.Which may be protective factors of AD.