Most patients with hepatocellular carcinoma(HCC)are diagnosed at an intermediate or advanced stage,losing the opportunity for surgical resection.Conversion therapy,which uses non-surgical approaches to render initially unresectable tumors resectable,has gradually become part of routine clinical practice and a research focus.However,multiple challenges remain,including the lack of clear criteria for identifying"potentially resectable"cases,difficulty in selecting individualized systemic regimens from multiple approved options and determining whether to combine them with locoregional therapy,controversy over the necessity of surgery in patients achieving radiological complete response,the need for optimization of perioperative assessment and management,uncertainty in determining the optimal timing of surgery,and the absence of consensus on postoperative sequential systemic therapy regimens and duration.Addressing these issues requires multidisciplinary collaboration and high-quality evidence from multicenter randomized controlled trials.With the accumulation of clinical experience,growing evidence,and advances in treatment,more patients with initially unresectable HCC are expected to gain surgical opportunities and achieve long-term disease-free survival.

Sepsis is a life-threatening organ dysfunction syndrome caused by a dysregulated host response to infection. Septic acute kidney injury (SAKI) is one of the most common complications of sepsis, and the occurrence of acute kidney injury (AKI) indicates that the patient's condition is critical with a poor prognosis. The traditional view holds that the main mechanism of SAKI is the reduction of renal blood flow, inadequate renal perfusion, inflammatory response, and microcirculatory dysfunction caused by sepsis, which subsequently leads to ischemia and necrosis of renal tubular cells. Recent research findings indicate that processes such as autophagy and other forms of programmed cell death play an increasingly important role. Autophagy is a programmed intracellular degradation process and is a form of programmed cell death. Cells degrade their cytoplasmic components via lysosomes, breaking down and recycling intracellular constituents to meet their metabolic needs, maintain intracellular homeostasis, and renew organelles. During SAKI, autophagy plays a crucial protective role through various mechanisms, including regulating inflammation and immune responses, clearing damaged organelles, and maintaining stability in the intracellular environment. In recent years, the role of autophagy in the pathogenesis and treatment of SAKI has received widespread attention. Research has confirmed that various intracellular signaling pathways and signaling molecules targeting autophagy [such as mammalian target of rapamycin (mTOR) signaling pathway, AMP-activated protein kinase (AMPK) signaling pathway, nuclear factor-κB (NF-κB) signaling pathway, and Sirtuins (SIRT), autophagy associated factor Beclin-1, and Toll-like receptor (TLR)] are involved in the development of SAKI. Due to the complex pathogenesis of SAKI, current treatment strategies include fluid management, infection control, maintenance of internal environment balance, and renal replacement therapy; however, the mortality remains high. In recent years, it has been found that autophagy plays a critical protective role in sepsis-mediated AKI. As a result, an increasing number of drugs are being developed to alleviate SAKI by regulating autophagy. This article reviews the latest advances in the role of autophagy in the pathogenesis and treatment of SAKI, with the aim of providing insights for the development of new drugs for SAKI patients.
Humans ; Acute Kidney Injury/etiology* ; Autophagy ; Sepsis/complications* ; Signal Transduction

BACKGROUND:Primary osteoporosis has a high incidence,but the pathogenesis is not fully understood.Currently,there is a lack of effective early screening indicators and treatment programs. OBJECTIVE:To further explore the mechanism of primary osteoporosis through comprehensive bioinformatics analysis. METHODS:The primary osteoporosis data were obtained from the gene expression omnibus(GEO)database,and the differentially expressed genes were screened for Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.In addition,the differentially expressed genes were subjected to protein-protein interaction network to determine the core genes related to primary osteoporosis,and the least absolute shrinkage and selection operator algorithm was used to identify and verify the primary osteoporosis-related biomarkers.Immune cell correlation analysis,gene enrichment analysis and drug target network analysis were performed.Finally,the biomarkers were validated using qPCR assay. RESULTS AND CONCLUSION:A total of 126 differentially expressed genes and 5 biomarkers including prostaglandins,epidermal growth factor receptor,mitogen-activated protein kinase 3,transforming growth factor B1,and retinoblastoma gene 1 were obtained in this study.GO analysis showed that differentially expressed genes were mainly concentrated in the cellular response to oxidative stress and the regulation of autophagy.KEGG analysis showed that autophagy and senescence pathways were mainly involved.Immunoassay of biomarkers showed that prostaglandins,retinoblastoma gene 1,and mitogen-activated protein kinase 3 were closely related to immune cells.Gene enrichment analysis showed that biomarkers were associated with immune-related pathways.Drug target network analysis showed that the five biomarkers were associated with primary osteoporosis drugs.The results of qPCR showed that the expression of prostaglandins,epidermal growth factor receptor,mitogen-activated protein kinase 3,and transforming growth factor B1 in the primary osteoporosis sample was significantly increased compared with the control sample(P<0.001),while the expression of retinoblastoma gene 1 in the primary osteoporosis sample was significantly decreased compared with the control sample(P<0.001).Overall,the study screened and validated five potential biomarkers of primary osteoporosis,providing a reference basis for further in-depth investigation of the pathogenesis,early screening and diagnosis,and targeted treatment of primary osteoporosis.

Objective:To explore the medication adherence of elderly patients with chronic diseases and polypharmacy in rural areas of Hangzhou City and analyze its influencing factors.Methods:From April to July 2023, convenience sampling was used to select rural 240 elderly patients with chronic diseases and polypharmacy in five administrative districts (counties) of Hangzhou as participants. The survey was conducted using the General Information Questionnaire, Social Support Rating Scale, Medication Knowledge and Beliefs Questionnaire, and the Chinese version of the 8-item Morisky Medication Adherence Scale. Multiple linear regression was used to analyze the factors influencing medication adherence in elderly patients with chronic diseases and polypharmacy in rural areas of Hangzhou City.Results:A total of 240 questionnaires were distributed and 220 valid questionnaires were collected, with an effective response rate of 91.67%. Among 220 elderly patients with chronic diseases and polypharmacy in rural areas of Hangzhou City, 135 had poor medication adherence. Multiple linear regression analysis showed that age, educational level, family doctor contract, medication knowledge, and beliefs were the influencing factors of medication adherence in elderly patients with chronic diseases and polypharmacy in rural areas of Hangzhou City ( P<0.05) . Conclusions:The medication adherence of elderly patients with chronic diseases and polypharmacy in rural areas of Hangzhou urgently needs to be improved. Medical and nursing staff should pay special attention to patients who are old, have a low level of education, have not signed a family doctor, and have poor knowledge and beliefs about medication. It is suggested that the contract system for family doctors be further promoted, focusing on health education on medication knowledge and beliefs, to improve medication adherence among elderly chronic disease patients in rural areas.

Objective:To explore the medication adherence of elderly patients with chronic diseases and polypharmacy in rural areas of Hangzhou City and analyze its influencing factors.Methods:From April to July 2023, convenience sampling was used to select rural 240 elderly patients with chronic diseases and polypharmacy in five administrative districts (counties) of Hangzhou as participants. The survey was conducted using the General Information Questionnaire, Social Support Rating Scale, Medication Knowledge and Beliefs Questionnaire, and the Chinese version of the 8-item Morisky Medication Adherence Scale. Multiple linear regression was used to analyze the factors influencing medication adherence in elderly patients with chronic diseases and polypharmacy in rural areas of Hangzhou City.Results:A total of 240 questionnaires were distributed and 220 valid questionnaires were collected, with an effective response rate of 91.67%. Among 220 elderly patients with chronic diseases and polypharmacy in rural areas of Hangzhou City, 135 had poor medication adherence. Multiple linear regression analysis showed that age, educational level, family doctor contract, medication knowledge, and beliefs were the influencing factors of medication adherence in elderly patients with chronic diseases and polypharmacy in rural areas of Hangzhou City ( P<0.05) . Conclusions:The medication adherence of elderly patients with chronic diseases and polypharmacy in rural areas of Hangzhou urgently needs to be improved. Medical and nursing staff should pay special attention to patients who are old, have a low level of education, have not signed a family doctor, and have poor knowledge and beliefs about medication. It is suggested that the contract system for family doctors be further promoted, focusing on health education on medication knowledge and beliefs, to improve medication adherence among elderly chronic disease patients in rural areas.

Most patients with hepatocellular carcinoma(HCC)are diagnosed at an intermediate or advanced stage,losing the opportunity for surgical resection.Conversion therapy,which uses non-surgical approaches to render initially unresectable tumors resectable,has gradually become part of routine clinical practice and a research focus.However,multiple challenges remain,including the lack of clear criteria for identifying"potentially resectable"cases,difficulty in selecting individualized systemic regimens from multiple approved options and determining whether to combine them with locoregional therapy,controversy over the necessity of surgery in patients achieving radiological complete response,the need for optimization of perioperative assessment and management,uncertainty in determining the optimal timing of surgery,and the absence of consensus on postoperative sequential systemic therapy regimens and duration.Addressing these issues requires multidisciplinary collaboration and high-quality evidence from multicenter randomized controlled trials.With the accumulation of clinical experience,growing evidence,and advances in treatment,more patients with initially unresectable HCC are expected to gain surgical opportunities and achieve long-term disease-free survival.

Objective To construct type Ⅰ collagen gels with different stiffness and to investigate the effects of three-dimensional(3D)culture environments of the gels on the morphology,free migration ability,and cell killing function of natural killer(NK)cells.Methods Type Ⅰ collagen was isolated from the tails of Sprague Dawley(SD)rats and collagen gels with different levels of stiffnesses were prepared accordingly.The microstructure of the collagen gels was observed by laser confocal microscopy.The stiffness of the collagen gels was assessed by measuring the plateau modulus with a rheometer.NK-92MI cells were cultured in collagen gels with different levels of stiffness.The morphology of NK-92MI cells was observed by inverted microscope.High content imaging system was used to record the free migration process of NK-92MI cells and analyze the migration speed and distance.NK-92MI cells were cultured with type Ⅰcollagen gels with different levels of stiffness for 24 h and 48 h and,then,co-cultured with human colorectal DLD-1,a human adenocarcinoma epithelial cell line.CCK8 assay was performed to determine the proliferation rate of DLD-1 cells and analyze the cell killing ability of NK-92MI cells.Results Low-stiffness type Ⅰ collagen gel and high-stiffness type Ⅰcollagen gel with the respective stiffness of(10.970±2.10)Pa and(114.50±3.40)Pa were successfully prepared.Compared with those cultured with the low-stiffness type Ⅰ collagen gel,the NK-92MI cells in the high-stiffness type Ⅰ collagen gel showed a more elongated shape(P<0.05),the mean area of the cells was reduced([69.88±26.97]μm2 vs.[46.59±21.62]μm2,P<0.05),the roundness of the cells decreased(0.82±0.12 vs.0.78±0.18,P<0.05),cell migration speed decreased([2.50±0.91]μm/min vs.[1.70±0.72]μm/min,P<0.001)and the migration distance was shortened([147.10±53.74]μm vs.[98.03±40.95]μm,P<0.0001),with all the differences being statistically significant.Compared with those cultured with the low-stiffness type Ⅰ collagen gel,NK-92MI cells cultured with high-stiffness type Ⅰ collagen gel for 24 h could promote DLD-1 cell proliferation,with the proliferation rate being(46.39±12.79)%vs.(65.87±4.45)%(P<0.05)and reduce the cell killing ability.Comparison of the cells cultured for 48 h led to similar results,with the proliferation rates being(31.36±2.88)%vs.(74.57±2.16)%(P<0.05),and the differences were all statistically significant.Conclusion The 3D culture environment of type Ⅰ collagen gels with different levels of stiffness alters the morphology,migration ability,and killing function of NK-92MI cells.This study provides the research basis for exploring and understanding the mechanisms by which the biomechanical microenvironment affects the immune response of NK cells,as well as laying the theoretical foundation for optimizing immunotherapy protocols.

Objective To evaluate the perioperative application of enhanced recovery after surgery(ERAS)in patients with valvular heart disease systematically through Meta-analysis.Methods Randomized controlled trials investigating the use of ERAS protocols during the perioperative period in patients with valvular heart disease were searched,including China Knowledge Network,WanFang Database,and China Biomedical Literature Databas,eight databases spanning literature from January 2015 to June 2024.Two researchers conducted an independent review of the literature and extracted pertinent data.A Meta-analysis was conducted by using RevMan 5.4 software on the selected studies.Results A total of 26 studies,involving 2664 participants analyzed.The Meta-analysis revealed that patients in ERAS group experienced a significant reduction in postoperative time to first defecation and bowel movement,as well as a quicker time to first ambulation,reduced hospital stay duration,and fewer postoperative complications.Additionally,there was a notable improvement in patients'quality of life.Conclusion The application of ERAS protocols in patients undergoing heart valve surgery markedly promote recovery,reduce the frequency of complications,and improve overall standard of living.

Antimicrobial peptides (AMPs) are small molecular peptides widely existing in the innate immunity of organisms, serving as the first line of defense. Natural AMPs possess various biological activities and are difficult to develop drug resistance. However, they are easily broken down by digestive enzymes in the body. In recent years, increasing methods have been reported to enhance the stability of AMPs, including incorporation of unnatural amino acids, chemical modifications, strategic avoidance of enzyme cleavage sites, cyclization, and nano peptide design. This review summarizes the methods for improving the stability of AMPs against protease degradation, aiming to provide references for further research in this field.
Antimicrobial Peptides/pharmacology* ; Humans ; Peptide Hydrolases/metabolism* ; Protein Stability ; Antimicrobial Cationic Peptides/chemistry* ; Anti-Infective Agents/chemistry*

Objective To establish a personalized Stanford type B aortic dissection numerical simulation model, and using computational fluid dynamics (CFD) numerical simulation to obtain the hemodynamic behavior and law of the type B aortic dissection at different stages of development. Methods Based on the theory of three-dimensional model reconstruction, we used CT images of a patient with type B aortic dissection in the Xiamen Cardiovascular Hospital of Xiamen University, relevant medical image processing software to reconstruct a personalized aortic three-dimensional model, and CFD to reconstruct the model which was simulated in fluid mechanics. Results The three-dimensional reconstruction model could intuitively observe the changing trend of the false cavity at different stages of the dissection development. Through fluid mechanics simulation, the blood flow rate, pressure, wall shear stress, vascular wall Von Mises stress and other parameters at different stages of the dissection development were obtained. Conclusion The hemodynamic behavior and law of relevant parameters in the development stage of aortic dissection are analyzed. The combination of the values of relevant parameters and clinical medical detection and diagnosis can well predict the development of the disease, and finally provide more theories and methods for the scientific diagnosis of aortic dissection.