Hepatocellular carcinoma (HCC) is a lethal cancer with high morbidity rates worldwide. It is a major threat to public health in China, due to the combination of known and new risk factors, such as endemic hepatitis B virus (HBV), dietary aflatoxin exposure, and the occurrence of metabolic dysfunction-associated steatotic liver disease (MASLD). Although many methods for surveillance and multimodal therapies, such as surgery, local ablation, transarterial therapy, and new systemic agents, have been available, the survival rates of HCC remains poor. They have very limited durable responses, long post-treatment recurrence rates, and high resistance to treatment. This reflects an imperfect picture of the biological cause of the disease and a need for new mechanistic or targeted techniques. A significant characteristic of HCC, in common with other aggressive cancers, is the presence of reprogrammed, hyperactive cell metabolism. Tumor cells hijack metabolic pathways to promote their uncontrolled growth, stress survival, invasion and metastasis. While classical mechanisms such as the Warburg effect, lipid metabolism and glutamine utilization have been understood, the lysosome, which was once viewed as a static “waste disposal unit” to remove old organelles and proteins, is instead a dynamic signaling and metabolic core. The lysosomes incorporate nutrients, energy and stress signals by master regulators such as mTORC1 (activated on its surface) that balance anabolic growth and catabolic recycling to the cellular demands. In HCC, lysosomes are not passive, but are highly active and dysregulated. HCC cells upregulate lysosomes, which scavenge intracellular components via enhanced autophagy and engulf extracellular proteins via macropinocytosis, crucial for survival in the nutrient-poor, hypoxic tumor microenvironment. In addition to metabolism, lysosomes exhibit pro-invasive functions by secreting hydrolases to remodel the extracellular matrix, promote angiogenesis, and suppress stromal immune cells to foster a pro-tumor microenvironment. In a clinical context, lysosomes play an important role in therapeutic resistance: they sequester and inactivate chemotherapeutics via lysosomal sequestration, and enhanced autophagic flux protects the cell from therapy-induced damage, contributing to relapse, as lysosomal dysfunction is a key cause of treatment failure. This makes lysosomes promising yet challenging therapeutic targets in HCC. Recent preclinical and early clinical studies investigate multiple strategies to exploit the susceptibility of lysosomes: lysosome-specific agents, alkalinizing the lysosome lumen or inducing membrane permeabilization and lysosome-dependent cell death; pharmacological inhibition of key lysosomal enzymes or autophagy to impair nutrient recycling and stress adaptation; smart nanotherapeutic agents or antibody-drug conjugates, specifically activated in the acidic lysosomal environment or utilizing lysosomal pathways for efficient intracellular drug release; and combination strategies of lysosome-targeting agents with tyrosine kinase inhibitors or immunotherapy to overcome resistance and achieve synergistic antitumor effects. In summary, our review systematically presents the role of lysosomes in HCC, from metabolic reprogramming and microenvironmental adaptation to therapeutic resistance. By synthesizing the latest mechanistic insights and preclinical advances, this review highlights the indispensable role of lysosomes in the complex HCC biological network, emphasizing that an in-depth understanding of this dynamic organelle holds great promise for developing innovative, targeted therapies, offering new hope for improving the poor prognosis of global HCC patients.

Clinical death refers to the permanent cessation of life functions. This article reviews the definition of clinical death and the various scenarios in which it occurs, classifies the process of clinical death, and discusses the criteria for determining uncontrollable cardiac death, controllable cardiac death and the criteria and workflow for determining brain death. It elaborates on the relationship between brain death and death, and proposes the areas to note when standardizing the medical documentation of death cases. Based on this, it introduces the content of the management system and workflow construction for death determination in medical institutions, including management structure, personnel qualifications, document norms, quality control system and training mechanism. Paying attention to the construction of the management system and workflow for death determination in medical institutions is of great significance for ensuring medical quality and safety, promoting the healthy development of organ donation, and maintaining the seriousness of legal and ethical practices.

ObjectiveHistorically documented Zhejiang Atractylodis Macrocephalae Rhizoma（Baizhu） possesses premium characteristics such as phoenix-like head and crane-like neck， pronounced sweetness， and fragrant aroma. However， its current market circulation is low， and the processed products with Zhejiang-style characteristics are at the risk of being lost. This study aims to preserve the ancient Zhejiang-style processing techniques and evaluate them using modern scientific methods. MethodsMultidimensional intelligent sensory evaluation was used to digitally characterize the "quality-structure" of the external appearance of nine-steamed and nine-processed Baizhu medicinal materials（intermediate processed products） and the "odor-taste" of the internal quality of its decoction pieces（slices）， and the appearance parameters were digitally characterized by colorimeter， texture analyzer， electronic nose and electronic tongue， the chemical composition was analyzed via ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）. Then， cluster analysis on the differences in odor between the medicinal materials（intermediate processed products） and decoction pieces（slices） of nine-steamed and nine-processed Baizhu was conducted， as well as the differences in taste between water-soluble and alcohol-soluble extracts of the decoction pieces（slices）， and the correlation analysis of chroma value-alcohol-soluble extract content-component response value. ResultsThe nine-steamed and nine-processed Baizhu had a dark brown to black epidermis， a brownish-yellow to brownish-gray cross-section， a slightly tough texture， a faint odor， and a slightly sweet， bitter and pungent taste. Texture analyzer measurements revealed minimal adhesion and maximum recovery in the middle section of the characteristic processed Baizhu， consistent with the processing endpoint of thorough steaming and cooking. The head section showed the highest internal hardness， elasticity and chewiness， indicating a denser texture in this area. The electronic nose sensor could clearly distinguish the difference between the medicinal materials and its decoction pieces， with a more significant clustering effect at 60 ℃ for 30 minutes compared to ambient temperature headspace for 2 hours， highlighting the significant impact of the baking degree before slicing on the quality. The electronic tongue taste signal map clearly distinguished the differences between water-soluble and alcohol-soluble extracts of nine-steamed and nine-processed Baizhu decoction pieces， and the addition of auxiliary materials during processing could enhance its alcohol-soluble extract content. A total of 82 chemical components were identified in the characteristic processed Baizhu. After processing， the contents of 58 components increased， while 24 components decreased. Correlation analysis revealed significant negative correlations（P<0.01） between ethanol-soluble extract content and colorimetric values of brightness（L^*）， yellow-bule value（b^*）， and total color difference（E^*_ab）. E^*_ab showed marked negative correlations（P<0.05） with the response values of isochlorogenic acid A and C. ConclusionThis study establishes a modern intelligent sensory evaluation model for multidimensional holographic characterization of nine-steamed and nine-processed Baizhu， clarifying the correlation between increased isochlorogenic acid content and the visual color appearance after different steaming cycles， as well as its intrinsic alcohol-soluble extracts. This provides a reference for quality evaluation and processing standards of the Zhejiang-style characteristic processed products.

Objective: Huntington’s disease (HD) is characterized by motor, cognitive, and neuropsychiatric symptoms. Oculomotor impairments and gait variability have been independently considered as potential markers in HD. However, an integrated analysis of eye movement and gait is lacking. We performed multiple examinations of eye movement and gait variability in HTT mutation carriers, analyzed the consistency between these parameters and clinical severity, and then examined the associations between oculomotor impairments and gait deficits. Methods: We included 7 patients with pre-HD, 30 patients with HD and 30 age-matched controls. We collected demographic data and assessed the Unified Huntington’s Disease Rating Scale (UHDRS) score. Examinations, including saccades, smooth pursuit tests, and optokinetic (OPK) tests, were performed to evaluate eye movement function. The parameters of gait include stride length, walking velocity, step deviation, step length, and gait phase. Results: HD patients have significant impairments in the latency and velocity of saccades, the gain of smooth pursuit, and the gain and slow phase velocities of OPK tests. Only the speed of saccades significantly differed between pre-HD patients and controls. There are significant impairments in stride length, walking velocity, step length, and gait phase in HD patients. The parameters of eye movement and gait variability in HD patients were consistent with the UHDRS scores. There were significant correlations between eye movement and gait parameters. Conclusion Our results show that eye movement and gait are impaired in HD patients and that the speed of saccades is impaired early in pre-HD. Eye movement and gait abnormalities in HD patients are significantly correlated with clinical disease severity.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective To analyze the current status and emerging technology trends in domestic medical drainage tube patents,so as to explore possible factors for low patent conversion rates.Methods Patents associated with"drainage tube","medical drainage tube","surgical drainage tube"and related terms were retrieved from the National Intellectual Property Administration Database and the Innojoy Patent Search Engine,covering the period from 2010 to 2020.Screening and visual analysis were conducted using Excel and SPSS 27.0.Results A total of 2 895 relevant patents were identified,comprising 2 489 utility model patents,367 invention patents and 39 design patents.The number of patent applications demonstrated a year-on-year growth trend,with a higher concentration in eastern coastal regions and provinces housing numerous top-tier hospitals and medical institutions.Approximately 49.26％of the patents filed by individuals were affiliated with hospitals,universities,or enterprises.Innovation hotspots included the design,functionality,performance,and safety aspects of drainage tubes and probes.Of the patents,72.61％were invalid,and 61.73％had a survival period of three years or less.Only 5.15％were commercially utilized through transfers,pledges,or licensing.Conclusion Domestic patent applications for medical drainage tubes have seen rapid growth,with a focus on enhancing tube structures such as sleeves,balloons,drainage holes,and threaded designs.However,the unsatisfactory situation of patent conversion and operation have been mainly limited by factors such as weak core technology of patents,insufficient awareness of achievements conversion,poor operation of patent conversion mechanism,insufficient market promotion,and insufficient integration of industry,academia,and research.To address this issue,enhancing intellectual property protection,revitalizing valid patents,and expanding transformation channels would benefit patients and facilitate hospitals'high-quality development,injecting new vitality into the health industry.

OBJECTIVE To analyze the differences in chemical composition of mussels from Shengsi,Zhoushan in different har-vest months,and to compare the differences in the composition of mussels from different origins,so as to provide ideas for the compre-hensive utilization of its resources.METHODS Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry(UHPLC-QqQ-MS)and spectrophotometry were used to analyze and evaluate the contents of nucleosides,amino acids,water-soluble proteins,total sugars and polysaccharides in mussels from Shengsi,Zhoushan in 12 months of the year and from 5 different origins;principal component analysis(PCA),partial least squares discriminant method(PLS-DA)and TOPSIS method were used to compre-hensively evaluate mussels.RESULTS A total of 16 amino acids and 11 nucleosides were detected in mussels.The average content of total amino acids in Shengsi mussels throughout the year was 4 851.74 μg·g-1,the average content of total nucleosides was 921.40 μg·g-1,and the average contents of water-soluble protein,polysaccharides,and total sugars were 51.32 mg·g-1,74.39 μg·g-1,and 417.22 mg·g-1,respectively.The nucleosides of Shengsi mussels were the highest in March and April,the ami-no acids and water-soluble proteins were the highest in April and May,and the polysaccharides and total sugars were the highest in Oc-tober and November.The PCA and PLS-DA results of the chemical components of different resources showed that there were great differences in Shengsi mussel samples harvested in different seasons.The entropy weight TOPSIS analysis showed that the comprehen-sive scores of Shengsi mussels in March and April(S7 and S8)were better than those in other areas,and the comprehensive score of Shengsi mussels in April(S8)was the highest,which was determined to be the best harvesting month.CONCLUSION The comparison results of multi-type resource chemistry show that there are great differences in the chemical compo-sition of Shengsi mussels in different harvesting seasons;the quality of Shengsi mussels is better than that of other areas;April is the best harvesting season,providing a reference for the quality evaluation and comprehensive development and utilization of mussels.

Objective To define the operation scale of the biochemical test project based on the risk model,and design the statistical quality control(SQC)strategy by rationally adjusting the risk factors.Methods The σ(σ)values for the biochemistry test items were calculated based on the imprecision(CV)of internal quality control(IQC),external quality assessment(EQA)offset bias(Bias)and allowable total error(TEa)of CLIA 2019.By evaluating and adjusting the patient risk factors,designed the SQC for multiple test biochemical items representing high σ,medium σ and low σ categories.Results Clinical biochemistry testing items with different QC levels showed different σ performance,with values for P and K quality control levels 2 higher than level 1 and the remaining items all had very similar.18 projects for risk σ≥4.96:CK,LDH,GGT,AMY,AST,MG,TG,TBIL,FE,NA,UA,CREA,P,ALP,K,ALT and CA,respectively.Controlled with a QC program 13s N=2,run size was 179～1 000 samples.ALB,GLU,CL,TP and UREA need to achieve the expected operational scale by adjusting for risk factors.Conclusion The laboratory can combine program testing performance and patient safety goals,design SQC strategies for clinical biochemistry testing programs by rationally adjusting risk factors,apply as few SQC procedures for as much testing as possible,and align the laboratory workload and reporting interval with the number of patient samples.

It has been not been updated for nearly 5 years since the Pharmacoepidemiology Professional Committee of the Chinese Pharmaceutical Association released the Guide on Methodological Standards in Pharmacoepidemiology in China(1st edition)in 2019,and an update is urgently needed.This study adopts a systematic review approach to comprehensively search for global pharmacoepidemiology methodological guidelines and analyze their development status.By extracting the frameworks and key elements of the guidelines,the China's guide was compared with other included guidelines,its shortcomings were analysed,and pragmatic and feasible suggestions for improvement in line with China's national conditions,were proposed in order to provide references for updating China's guide.A systematic search was conducted by searching PubMed,Embase,CNKI,WanFang Data and 17 official websites of international academic organizations for pharmacoepidemiology and regulatory agencies from countries or regions including Europe,the United States,Japan,and China,etc.,and relevant guidelines or standards were screened based on predefined inclusion and exclusion criteria,resulting in the inclusion of 33 methodological guidelines or standards for pharmacoepidemiological studies.A qualitative synthesis approach was then employed to extract core elements from the guidelines through thematic categorization and content summarization,followed by a descriptive comparative analysis.The results indicate that the 1st edition of the China's guide provides relatively comprehensive guidance on adverse drug reaction reporting and publication of research findings.However,there are gaps in study protocol development,data analysis during study implementation,study reporting,and specific study scenarios.By integrating and drawing upon the latest international pharmacoepidemiology methodology guidelines while balancing comprehensiveness,practicality,and user-friendliness,this study provides recommendations for updating the China's guide.