ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

OBJECTIVE To standardize the strategies for prevention and control of Chikungunya(CHIK)in healthcare in-stitutions so as to reduce the risk of transmission in the institutions.METHODS A working group comprising the ex-perts in hospital infection control,infectious diseases,and microbiology systematically reviewed domestic and international evidence and current guidelines,integrated China's vector ecology and healthcare realities,conducted two rounds of Delphi to achieve expert consensus,and graded the evidence and recommendation strength using the Oxford Centre for Evidence Based Medicine system.RESULTS The consensus issues 18 actionable recommendations on triage,patient mosquito-proof isolation,integrated vector control,protection of susceptible populations,environmental cleaning and disinfection,specimen management,medical textile handling,and outbreak emergency response,with each statement assigned an evi-dence level and recommendation strength.CONCLUSION This consensus is for the first time in China to provide evidence-graded strategies for control of CHIK in healthcare institutions,offering work flow-oriented,implementable guidance for clinicians,laboratorians,and infection-control personnel under different risk scenarios and enhancing the comprehensive coping capacity of the healthcare institutions.

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

This article elucidates therapeutic approaches for KRAS G12C-mutant advanced non-small cell lung cancer, with focus on global advancements in inhibitor research. It also summarizes clinical evidence on the efficacy of targeted agents in monotherapy and combination therapies, analyzes their clinical advantages and challenges, and explores future directions for novel treatment modalities.

As a new generation of time-of-flight mass spectrometry,multiple-reflection time-of-flight mass spectrometry(MR-TOF-MS)has been increasingly applied in the fields such as nuclear physics,chemistry,and biology due to its ultra-high resolution and rapid analysis capabilities.However,the analytical performance of MR-TOF-MS largely depends on the ion bunch state entering the mass analyzer.In this study,a rectangular ion trap(RIT)was developed,designed and processed using printed circuit board technology,as an ion accumulating and focusing device for MR-TOF mass analyzer.Compared to traditional ion traps composed of two sets of planar electrodes,this RIT had higher voltage utilization efficiency,resulting in more efficient ion collection and focusing.The ions were cooled to a sufficiently small bunch for precise mass measurement with MR-TOF-MS mass spectrometry in only 1 ms of cooling time in the RIT,then orthogonally ejected to the MR-TOF mass spectrometer for mass analysis.Experimental results indicated that the working cycle,ion flux,and ion focusing state of the RIT fully met the requirements of the MR-TOF mass analyzer.When coupled with the MR-TOF mass analyzer,the RIT enabled MR-TOF-MS to achieve a mass resolution of 1.5×105.

Managing look-alike/sound-alike medications is important to medical institutions'pharmaceutical manage-ment and pharmacy services.Based on national policies and regulations,this standard focuses on the whole life cycle of look-alike/sound-alike medications in medical institutions.It is developed based on the principles of scientific validity,universality,guidance,and applicability,formed by sorting out problems,soliciting opinions,expert argumentation,and deliberation.It is the first group standard to standardize the management of look-alike/sound-alike medications.This paper introduced and analyzed the team com-position,problem sorting and compilation process,and various elements of the standard in the process of formulating the standard,to provide a reference for medical institutions to use this standard.

Objective:To investigate the factors influencing left atrial fibrosis in patients with atrial fibrillation(AF)and the association of Periostin protein,serum transforming growth factor-β2(TGF-β2)with left atrial fibrosis.Methods:We enrolled 100 AF patients admitted to Gansu Provincial People's Hospital between March 2021 and March 2023.They were divided into control group(＜10％,n=53)and fibrosis group(≥10％,n=47)according to their left atrial low voltage region.Univariate and multivariate Logistic regression were used to analyze the influ-encing factors of left atrial fibrosis in AF patients and construct a nomogram model.The diagnostic value of related factors and their combined detection for left atrial fibrosis in AF patients were analyzed by receiver operating char-acteristic curve(ROC).Spearman correlation analysis was used to analyze the association of Periostin protein,TGF-β2 with left atrial fibrosis in AF patients.Results:Compared to patients in the control group,those in the fibrosis group had significant higher left atrial diameter(LAD)[(37.08±3.19)mm vs.(33.45±2.45)mm],levels of ser-um uric acid(SUA)[(313.75±49.06)μmol/L vs.(279.88±38.15)μmol/L],Periostin protein[(83.27±3.98)ng/L vs.(75.21±3.04)ng/L],TGF-β2[(4346.84±321.34)ng/L vs.(4186.02±306.91)ng/L],and signifi-cant lower left atrial ejection fraction(LVEF)[(62.28±5.00)％vs.(67.24±3.07)％](P＜0.05 or＜0.01).Multivariate Logistic regression analysis showed that LAD(OR=1.663,95％CI 1.238～3.887,P=0.001),SUA(OR=1.586,95％CI 1.164～2.892,P＜0.001),Periostin protein(OR=1.997,95％CI 1.513～4.585,P=0.001),TGF-β2(OR=2.013,95％CI 1.543～5.864,P＜0.001)were independent risk factors for left atrial fi-brosis in AF patients,while LVEF was an independent protective factor(OR=0.524,95％CI 0.141～0.920,P=0.002).The nomogram model for left atrial fibrosis in AF patients:logit(P)=4.631+0.445 × LVEF+0.546 × LAD+0.575 × SUA+0.530 × Periostin protein+0.347 × TGF-β2.ROC curve showed that the area under the curve(AUC)of combined detection(0.893,95％CI 0.842～0.932)was significantly higher than SUA(AUC=0.637,95％CI 0.566～0.704),LVEF(AUC=0.701,95％CI 0.632～0.763),LAD(AUC=0.649,95％CI 0.579～0.715),Periostin protein(AUC=0.676,95％CI 0.606～0.740),TGF-β2(AUC=0.641,95％CI 0.570～0.707)alone(Z=5.265,6.399,6.379,6.040,6.483,P＜0.001 all).Spearman correlation analysis showed that Perios-tin protein and TGF-β2 were significantly positive correlated with left atrial fibrosis in AF patients(r=0.536,0.578,P＜0.001 all).Conclusion:Periostin protein and TGF-β2 were independent risk factors for left atrial fi-brosis in AF patients and were significantly positive correlated with it,a combination of above-mentioned indexes,cardiac function indexes and uric acid had good diagnostic value for left atrial fibrosis.

Objective To investigate the mechanism of electroacupuncture-mediated PTEN-induced kinase 1(PINK 1)/Parkin signal pathway activation in treating functional dyspepsia model rats.Methods Thirty-six SD rats were randomly divided into the blank control(n=8)and the modeling groups(n=28)using the random number table method.The functional dyspepsia model was established using the compound etiology modeling method.After successful modeling,24 rats were divided into the model,electroacupuncture,and mosapride groups using the random number table method,with eight rats per group.The blank group was not intervened.The electroacupuncture,mosapride,and model groups were bound for 30 min,and only the electroacupuncture group was administered"Neiguan"(PC 6)and"Gongsun"(SP 4)while bound.The electroacupuncture and model groups were administered the same amount of normal saline,and the mosapride group was given mosapride citrate solution(1.35 mg/kg).The above intervention method were performed once a day for 7 consecutive days to observe the general condition of rats.Gastric emptying and small intestinal propulsion experiments were used to observe gastric emptying rate and small intestine propulsion rate in each group of rats.The interstitial cells of the Cajal(ICC)ultrastructure of gastric antrum were observed under a transmission electron microscope.The protein and mRNA expressions of C-kit proto-oncogene protein(C-kit),microtubule-associated protein 1 light chain 3(LC3)Ⅱ/Ⅰ,ubiquitin-binding protein p62(p62),Bcl-2 interacting protein 1(Beclin1),PINK1,and Parkin were detected using Western blotting and real-time fluorescence PCR.Results Compared with the blank group,the rats in the model group exhibited lethargy,dull and dry fur,sluggish responses,and substantial decreases in food intake and body weight.Their feces alternated between dry and loose consistency.Furthermore,the gastric emptying and small intestinal propulsion rates were reduced(P<0.01).The ultrastructural morphology of ICC and their mitochondria in the gastric antrum tissue showed apparent damage.The protein and mRNA expressions of C-kit and p62 were decreased(P<0.01),whereas those of PINK1,Parkin,Beclin1,and LC3Ⅱ/Ⅰ were increased(P<0.01).Compared with the model group,the rats in the electroacupuncture and mosapride groups showed notable improvements in their mental state,with neat fur,enhanced activity and responsiveness,gradual increases in food intake and body weight,and well-formed feces.Additionally,the gastric emptying and intestinal propulsion rates increased(P<0.01).The ultrastructural morphology of ICC and their mitochondria in the gastric antrum tissue were notably improved.The protein and mRNA expressions of C-kit and p62 were increased(P<0.01),whereas those of PINK1,Parkin,Beclin1,and LC3Ⅱ/Ⅰwere decreased(P<0.01).Conclusion Electroacupuncture improves the gastrointestinal motility of functional dyspepsia rats,and its mechanism may be related to upregulating C-kit and p62 expression,downregulating PINK1,Parkin,Beclin1,and LC3Ⅱ/Ⅰ expression,inhibiting abnormal PINK1/Parkin signal pathway activation,and blocking the excessive mitophagy of ICC.