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.

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.

A highly efficient oxidase-mimetic silver phosphate/nickel hydroxystannate(Ag3PO4/NiSn(OH)6)composite was synthesized via a precipitation method using nickel hydroxystannate(NiSn(OH)6)as the support.The abundant hydroxyl groups(—OH)on NiSn(OH)6 not only provided nucleation sites for Ag3PO4 nanoparticles but also improved their dispersion and overall material stability.Based on oxidase-like activity of Ag3PO4/NiSn(OH)6 and inhibitory effect of sodium dodecylbenzenesulfonate(SDBS)on this catalytic activity,a novel colorimetric sensing method for SDBS detection was developed.Under optimized experimental conditions,the method exhibited a linear range of 3.69-42.7 μmol/L,with a detection limit of 0.135 μmol/L(S/N=3).The regression equation was ΔA652=0.01125C(μmol/L)+0.1498,with a correlation coefficient(R2)of 0.992.Practical application in dishwashing liquid analysis achieved satisfactory recoveries of 96.9%-106.4%,demonstrating the method's reliability for real sample detection.

OBJECTIVE: This study aimed to evaluate the relationships of white blood cell (WBC) count, platelet (PLT) count, and PLT-to-WBC ratio (PWR) with muscle mass in Chinese older adults. METHODS: This cross-sectional analysis involved 4,033 Chinese older adults aged ≥ 65 years from the Healthy Ageing and Biomarkers Cohort Study. Muscle mass and total skeletal muscle mass index (TSMI) were measured by bioelectric impedance analysis. WBC, PLT, and PWR were measured using standard methods. Multivariate linear regression was used to examine the associations of WBC count, PLT count, and PWR with TSMI. RESULTS: High WBC count, PLT count, and PWR were associated with low TSMI, with coefficients of -0.0091 (95% confidence interval [ CI]: -0.0142 to -0.0041), -0.0119 (95% CI: -0.0170 to -0.0068), and -0.0051 (95% CI: -0.0102 to -0.0001). The associations between the three inflammatory indices and TSMI were linear. Stratified analyses indicated that the relationship between inflammatory markers and TSMI was more evident in male participants and in individuals aged < 80 years than in their counterparts. CONCLUSION Elevated WBC count, PLT count, and PWR correlated with muscle mass loss. This study highlights the importance of regular monitoring of inflammatory markers as a potential strategy for the screening and management of sarcopenia in older adults.
Humans ; Aged ; Male ; Female ; China ; Leukocyte Count ; Cross-Sectional Studies ; Platelet Count ; Aged, 80 and over ; Muscle, Skeletal/anatomy & histology* ; Independent Living ; Blood Platelets ; Leukocytes ; Sarcopenia

Objective:To investigate genetic findings and pregnancy outcomes in fetuses with omphalocele.Methods:This retrospective study analyzed data from 502 fetuses with prenatally diagnosed omphalocele who underwent genetic testing at Guangzhou Women and Children's Medical Center and Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region between January 2014 and March 2024. Testing methods included karyotyping, chromosomal microarray analysis (CMA), methylation-specific multiplex ligation-dependent probe amplification, and whole-exome sequencing (WES). Cases were categorized as non-isolated ( n=340) or isolated ( n=162) based on ultrasound findings. Differences in genetic abnormality detection rates and pregnancy outcomes were analyzed using Mann-Whitney U test, independent samples t-test, and Chi-square test (or Fisher's exact test). Results:Among 502 fetuses, karyotyping plus CMA detected chromosomal abnormalities in 223 cases (44.4%, 223/502), including trisomy 18 (57.0%, 127/223) and trisomy 13 (23.3%, 52/223). CMA additionally identified nine pathogenic copy number variations (1.8%, 9/502) and five uniparental disomies (1.0%, 5/502), increasing the total diagnostic yield from 44.4% to 47.2%. The genetic abnormality rate was significantly lower in isolated (14.8%, 24/162) versus non-isolated omphalocele (64.7%, 220/340) ( χ2=109.34, P<0.001). WES detected variants in nine of 16 karyotype/CMA-negative cases, including five pathogenic variants involving PIK3CA and CDKN1C. Eight imprinting disorders (1.6%, 8/502) were identified, including five Beckwith-Wiedemann syndrome cases. Among 499 cases with follow-up, 401 (80.4%, 401/499) underwent pregnancy termination. Live birth rate was higher in isolated versus non-isolated groups [42.5% (69/162) vs. 8.5% (29/340), χ2=77.67, P<0.001]. Three cases were lost to follow-up. The one-year survival rate was 93.9% (92/98) in live-born infants. Conclusion:Aneuploidy (particularly trisomy 18) is the primary genetic etiology of omphalocele. CMA and WES significantly improve diagnostic yield. Isolated omphalocele has a more favorable prognosis, while non-isolated cases show significantly higher genetic abnormality rates. A stratified testing strategy is recommended: karyotyping plus CMA for isolated cases and prioritization of WES for multiple anomalies.

Objective:To explore any effect of excitatory and inhibitory multi-focal transcranial direct current stimulation (m-tDCS) on cortical functioning in healthy adults.Methods:Fifteen healthy participants received 20-minute excitatory and inhibitory episodes of m-tDCS targeting C1-C2-FC1-FC2. Finite element analysis and functional near-infrared spectroscopy were then used to model the normal component of the electric field (En) applied and to monitor the oxygenated hemoglobin (HbO), deoxygenated hemoglobin (HbR), and total hemoglobin (THb) concentrations in the targeted regions during the stimulation.Results:The excitatory protocol induced En values of 0.057V/m and 0.058V/m in the left and right hemispheres, respectively, with an average of 0.058V/m, while the inhibitory one evoked corresponding En values of -0.057V/m and -0.058V/m with an average of -0.058V/m. During excitatory m-tDCS, HbO and THb concentrations in the target cortices were higher than in the inhibitory protocol, with significant differences at FC1, FC2, and C2 for HbO, and at FC2 and C2 for THb. However, no significant inter-group differences in HbR concentrations were observed. Moreover, either protocol induced severe adverse reactions including pain, though the pain decreased with prolonged stimulation.Conclusions:Both excitatory and inhibitory m-tDCS modulate cortical function among healthy individuals. Excitatory m-tDCS is the more effective in enhancing cortical excitability.

Objective:This study aimed to evaluate to evaluate the performance of equilibrium dialysis combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the accurate measurement of free testosterone in clinical samples. Mthods We conducted a prospective observational study using 161 serum samples from healthy women of reproductive 26(24, 32)years at the Gynecology Outpatient department of Peking Union Medical College Hospital from June to September 2024, and their concentrations were determined. In this study, after equilibrium dialysis of serum samples, free testosterone was extracted from the dialysate using a magnetic bead-based method. It was then directly derivatized using hydroxylamine hydrochloride in situ after elution from the magnetic bead and further quantified by LC-MS/MS.Method:validation assessed linearity, limit of quantification (LOQ), precision, accuracy, matrix effects, and carryover according to established guidelines. Data were analyzed using Origin 2019 and WPS Office 2019.Results:The method demonstrated excellent linearity ( R2>0.99) across 1-250 pg/ml with an LOQ of 1 pg/ml. The coefficients of variation for both intra-day and inter-day imprecision were less than 10% while recovery rates ranged from 92.60% to 99.10%. Matrix effect deviations were all within the range of 6% and carryover was negligible. Conclusions:In this study, the established method of magnetic bead-based extraction followed by in situ derivatization combined with liquid chromatography-tandem mass spectrometry performed well, and could be further applied to the detection of free testosterone concentration in childbearing age women.

Objective:To investigate and summarize the imaging and pathological features of non-acute occlusion following flow diverter (FD) implantation in animal models.Methods:Four experimental pigs (experimental group) that experienced non-acute occlusion (occlusion time exceeding 24 hours) within the FD stent implanted in the common carotid artery, and 19 pigs (control group) that did not experience stent occlusion during the same period were involved. Using an interventional approach under digital subtraction angiography (DSA), the 4 occluded FD lumens were mechanically opened. Optical coherence tomography (OCT), intravascular ultrasound (IVUS) and histopathological examinations were performed to evaluate the intraluminal composition and characteristics of the occlusive tissues. These findings were compared with non-occluded FD stents to summarize the imaging and pathological changes within the occluded FD lumen.Results:The occlusion times of the FD stents in the 4 experimental pigs were 16 weeks, 20 weeks, 20 weeks, and 24 weeks postoperatively. All occluded stents were successfully recanalized under DSA, with a technical success rate of 4/4. Among the 19 non-occluded FD stents, OCT and IVUS revealed uniform (16 stents) or non-uniform (3 stents) neointimal coverage of the stent struts, presenting as homogeneous high/slightly high signal intensity or medium echogenicity. Histopathological examination indicated that the neointima was primarily composed of smooth muscle cells and a small amount of fibrous connective tissues. In contrast, the 4 occluded FD stents demonstrated excessive neointimal proliferation and plaque formation, leading to luminal loss, as shown by OCT and IVUS. The occlusion tissues predominantly presented as homogeneous high signal intensity with weak attenuation (fibrous plaques) on OCT, with some regions showing blurred low signal intensity and strong attenuation (lipid plaques). IVUS presented homogeneous echogenicity (fibrous plaques) and hypoechogenic zones (lipid plaques). Histopathological examination showed that the occlusion tissues mainly consisted of smooth muscle cells, fibrous connective tissues, and lipids, accompanied by numerous foam cells and a minor presence of inflammatory cells.Conclusions:Histopathological examinations confirm that non-acute occlusion of FD is mainly caused by excessive hyperplasia of intima along with the formation of fibrous plaques and lipid plaques. OCT and IVUS have typical finding in imaging that can assist in determining the cause of stent occlusion as well as the lesion's nature, thereby providing crucial guidance for subsequent clinical treatment and drug selection.

Objective:To explore any effect of excitatory and inhibitory multi-focal transcranial direct current stimulation (m-tDCS) on cortical functioning in healthy adults.Methods:Fifteen healthy participants received 20-minute excitatory and inhibitory episodes of m-tDCS targeting C1-C2-FC1-FC2. Finite element analysis and functional near-infrared spectroscopy were then used to model the normal component of the electric field (En) applied and to monitor the oxygenated hemoglobin (HbO), deoxygenated hemoglobin (HbR), and total hemoglobin (THb) concentrations in the targeted regions during the stimulation.Results:The excitatory protocol induced En values of 0.057V/m and 0.058V/m in the left and right hemispheres, respectively, with an average of 0.058V/m, while the inhibitory one evoked corresponding En values of -0.057V/m and -0.058V/m with an average of -0.058V/m. During excitatory m-tDCS, HbO and THb concentrations in the target cortices were higher than in the inhibitory protocol, with significant differences at FC1, FC2, and C2 for HbO, and at FC2 and C2 for THb. However, no significant inter-group differences in HbR concentrations were observed. Moreover, either protocol induced severe adverse reactions including pain, though the pain decreased with prolonged stimulation.Conclusions:Both excitatory and inhibitory m-tDCS modulate cortical function among healthy individuals. Excitatory m-tDCS is the more effective in enhancing cortical excitability.

The rapid development of artificial intelligence (AI), especially generative AI (GenAI), has already brought, and will continue to bring, revolutionary changes to our daily production and life, as well as create new opportunities and challenges for diagnostic and therapeutic practices in the medical field. Haihe Hospital of Tianjin University collaborates with the National Supercomputer Center in Tianjin, Tianjin University, and other institutions to carry out research in areas such as smart healthcare, smart services, and smart management. We have conducted research and development of a full-process disease diagnosis and treatment assistance system based on GenAI in the field of smart healthcare. The development of this project is of great significance. The first goal is to upgrade and transform the hospital's information center, organically integrate it with existing information systems, and provide the necessary computing power storage support for intelligent services within the hospital. We have implemented the localized deployment of three models: Tianhe "Tianyuan", WiNGPT, and DeepSeek. The second is to create a digital avatar of the chief physician/chief physician's voice and image by integrating multimodal intelligent interaction technology. With generative intelligence as the core, this solution provides patients with a visual medical interaction solution. The third is to achieve deep adaptation between generative intelligence and the entire process of patient medical treatment. In this project, we have developed assistant tools such as intelligent inquiry, intelligent diagnosis and recognition, intelligent treatment plan generation, and intelligent assisted medical record generation to improve the safety, quality, and efficiency of the diagnosis and treatment process. This study introduces the content of a full-process disease diagnosis and treatment assistance system, aiming to provide references and insights for the digital transformation of the healthcare industry.
Artificial Intelligence ; Humans ; Delivery of Health Care ; Generative Artificial Intelligence