Objective To evaluate the efficacy and safety of CT-guided percutaneous radiofrequency ablation (RFA) as an alternative for video-assisted thoracoscopic surgery (VATS) in treating multiple pulmonary nodules. Methods A retrospective analysis was conducted on the clinical data of 113 patients with multiple pulmonary nodules admitted to Jiangsu Provincial Hospital of Traditional Chinese Medicine from October 2020 to October 2022. The patients were divided into the RFA group (n＝50) and the VATS group (n＝63) based on the treatment method. Perioperative indicators (operation time, intraoperative blood loss, postoperative length of hospital stay), oncological outcomes (recurrence-free survival [RFS], overall survival [OS]), and postoperative complication rates were compared between the two groups. Univariate and multivariate Cox regression analysis was performed to identify independent prognostic factors. Results The operation time in the RFA group was significantly shorter than that in the VATS group ([75.2±20.1] min vs [102.3±28.7]) min, P＜0.001). No statistically significant differences were observed in intraoperative blood loss and postoperative length of hospital stay. After follow-up of 24 (12, 30) months, no statistically significant differences were found in RFS (HR＝1.25, P＝0.445) or OS (HR＝1.42, P＝0.402) between the two groups. Mixed ground-glass nodules with high solid component and solid nodule were identified as independent risk factors for RFS (HR＝2.44, P＝0.023; HR＝2.97, P＝0.007) and OS (HR＝2.87, P＝0.022; HR＝3.43, P＝0.005) in patients with multiple pulmonary nodules. The total complication rate in the RFA group was lower than that in the VATS group (12.0% vs 34.9%, P＝0.009). Conclusions The efficacy of CT-guided RFA in treating multiple pulmonary nodules is comparable to that of VATS, with good safety, and it shows promise as an alternative to surgical treatment for multiple pulmonary nodules.

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.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

Brain’s neural activities encompass both periodic rhythmic oscillations and aperiodic neural fluctuations. Rhythmic oscillations manifest as spectral peaks of neural signals, directly reflecting the synchronized activities of neural populations and closely tied to cognitive and behavioral states. In contrast, aperiodic fluctuations exhibit a power-law decaying spectral trend, revealing the multiscale dynamics of brain neural activity. In recent years, researchers have made notable progress in studying brain aperiodic dynamics. These studies demonstrate that aperiodic activity holds significant physiological relevance, correlating with various physiological states such as external stimuli, drug induction, sleep states, and aging. Aperiodic activity serves as a reflection of the brain’s sensory capacity, consciousness level, and cognitive ability. In clinical research, the aperiodic exponent has emerged as a significant potential biomarker, capable of reflecting the progression and trends of brain diseases while being intricately intertwined with the excitation-inhibition balance of neural system. The physiological mechanisms underlying aperiodic dynamics span multiple neural scales, with activities at the levels of individual neurons, neuronal ensembles, and neural networks collectively influencing the frequency, oscillatory patterns, and spatiotemporal characteristics of aperiodic signals. Aperiodic dynamics currently boasts broad application prospects. It not only provides a novel perspective for investigating brain neural dynamics but also holds immense potential as a neural marker in neuromodulation or brain-computer interface technologies. This paper summarizes methods for extracting characteristic parameters of aperiodic activity, analyzes its physiological relevance and potential as a biomarker in brain diseases, summarizes its physiological mechanisms, and based on these findings, elaborates on the research prospects of aperiodic dynamics.

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 investigate the effects of hypoxia on the transcriptional phenotype and ultrastructure of tumor-associated macrophages(TAMs)in glioma.Methods CD14+monocytes were isolated from healthy human peripheral blood samples collected from the Blood Bank of the First Affiliated Hospital of Army Medical University,and the cells were induced to differentiate into TAMs through co-culture with glioma cell-conditioned medium.Hypoxic TAM models were established using varying concentrations of cobalt chloride hexahydrate(CoCl2,50～400 μmol/L)or hypoxic conditions(1%,5%,10%O2)for 48 h,while normoxic TAM models(21%O2)served as controls.RT-qPCR and transcriptome sequencing were employed to analyze transcriptional changes in TAMs under normoxic and hypoxic conditions.Gene set enrichment analysis(GSEA)was applied to compare the differences in angiogenesis,glycolysis and other hypoxia-responsive pathways between the 2 conditions.Transmission electron microscopy(TEM)or immunofluorescence staining was conducted to assess the ultrastructural alterations in cytoskeleton,endoplasmic reticulum(ER),and mitochondria in normoxic and hypoxic TAMs(1%O2).Results Hypoxic TAMs exhibited up-regulated transcription of hypoxia-responsive markers(oxygen transport,glycolysis,pro-angiogenesis),with the effects correlating with hypoxia severity(P<0.05).GSEA revealed significant up-regulation of hypoxia,angiogenesis regulation,glycolysis and gluconeogenesis,and starvation stress pathways,alongside down-regulation of innate immunity,macrophage activation,cytoskeleton,and protein maturation pathways in hypoxic TAMs(P<0.05).TEM and immunofluorescence staining demonstrated obvious ultrastructure changes,including disrupted cytoskeletal organization,shortened rough ER with reduced ribosomes,mitochondrial swelling with cristae damage,and diminished ER-mitochondria contacts in hypoxic TAMs.Conclusion CoCl2 and hypoxia induce a hypoxic transcriptional phenotype in TAMs,which may potentially associated with ultrastructural remodeling of the cytoskeleton,ER,and mitochondria.

Drug-induced liver injury(DILI)is a common adverse drug reaction in clinical practice,which can lead to acute liver failure and even death in severe cases.In recent years,with the continuous introduction of new drugs and the expansion of their usage,the incidence and mortality rates of DILI have shown an upward trend,posing significant challenges to public health and clinical treatment.Macrophages,as a crucial component of the innate immune system,exhibit high plasticity and heterogeneity.They can polarize into pro-inflammatory M1 type or anti-inflammatory M2 type in response to microenvironmental signals.Research has demonstrated that macrophage polarization plays a central regulatory role in the occurrence and progression of DILI by influencing various processes such as inflammatory responses,cell apoptosis,and tissue repair.This review focuses on elucidating the regulatory mechanisms and roles of macrophage polarization in DILI,providing a theoretical framework for developing precise immunotherapeutic strategies.

Objective To discuss the effect of different particle activities and tumor shrinkage speed on the dosimetric parameters of the target area at the same prescription dose after 125I particle implantation.Methods A 6cm-sized cube tumor model was outlined by using a computerized three-dimensional treatment planning system(3D-TPS)with a prescription dose(PD)of 100 Gy,and 125I particle activities of 0.4 mCi and 0.8 mCi were selected.Assuming that the tumor shrinks centripetally after seed implantation and that the 125I particles were uniformly and centripetally concentrated without shedding or wandering,the tumor volume shrank at different rates every month after implantation(0,5％,10％,15％,20％,25％,30％,35％,40％,45％and 50％),according to the different activities of 125I particles,the experiments were divided into A1-K1 group(0.4 mCi)and A2-K2 group(0.8 mCi).Based on the 125I particle decay law,the validation program(using TPS simulation of the A1-K1 group and A2-K2 group at postoperative 1,2,3,4,5 and 6 months)obtained the dose received by 90％of the target volume(D90)in the two groups with different 125I particle activities at different postoperative time points,the percentages of the target volume covered by the 100％,150％and 90％prescription dose(V100,V150,V90),and the mean dose(Dmean).By comparing the differences in D90,V100,V150,V90 and Dmean after tumor implantation of 125I particles with different activities,the dosimetric impact of the tumor target area shrinking at a rate of 0～50％after implantation of 125I particles with different activities into tumor tissues was analyzed.Results When the monthly shrinkage rate of the tumor target area was≤30％,there was no obvious difference in D90 between the 0.4 mCi group and 0.8 mCi group in 1～6 months after surgery.When the monthly shrinkage rate of the tumor target area was＞30％,the D90 of 0.8 mCi group was higher than that of 0.4 mCi group;when the monthly shrinkage rate of the tumor target area was＜25％,the V90 of 0.4 mCi group was higher than that of 0.8 mCi group,and the changes of V90 of the two groups tended to be the same in the 5th～6th month after surgery.When the monthly shrinkage rate of the tumor target area was ≥30％,the V90 of 0.8 mCi group was higher than that of 0.4 mCi group,and with the increasing of shrinkage rate,the difference between the two groups become more and more significant,the results of V100 were consistent with those of V90.When the monthly shrinkage rate of tumor target area＜35％,V150 of 0.4 mCi group was higher than that of 0.8 mCi group,when the monthly shrinkage rate of tumor target area ≥35％,V150 of 0.8 mCi group was higher than that of 0.4 mCi group,and with the increasing of shrinkage rate,the difference between the two groups become more and more prominent.When the monthly shrinkage rate of tumor target area＜25％,Dmean of 0.4 mCi group was higher than that of 0.8 mCi group,when the monthly shrinkage rate of tumor target area ≥25％,Dmean of 0.8 mCi group was higher than that of 0.4 mCi group,and with the increasing of shrinkage rate,the difference between the two groups become more and more obvious.Conclusion With the same prescription dose,when the tumor target area shrinks at a rate of＜30％per month,the activity of 125I particles has little effect on D90,and all V90,V100,V150 and Dmean in the low activity group are higher than those in the high activity group,meanwhile the homogeneity of the target area is relatively good;when the monthly shrinkage rate of tumor target area ≥35％,all D90,V90,V100,V150 and Dmean in the high activity group are higher than those in the low activity group,and the duration of the presence of high-dose area is long.This difference becomes more obvious with the increasing of the monthly shrinkage rate of the target area.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective:To investigate the changes in brain functional network and structural-functional network coupling in children with drug-resistant epilepsy (DRE), and to analyze their correlation with cognitive function, disease duration, and age of onset.Methods:This study was a cross-sectional study. Clinical and imaging data of 19 children with DRE who received consultation and treatment at the Affiliated Hospital of Zunyi Medical University from August 2021 to August 2023 (DRE group) were prospectively included. Another 27 age-and sex-matched healthy children were collected as the healthy control group. All subjects had 3D-T 1WI, T 2 fluid-attenuated inversion recovery, diffusion tensor imaging (DTI), resting-state functional magnetic resonance imaging (rs-fMRI) scans and Wechsler Intelligence Scale assessments. Independent sample t-test and Mann-Whitney U test were used to analyze the global and local topological attributes, as well as the structural-functional coupling (SFC) values at the whole brain and modular levels in two groups. Correlations between abnormal resting state brain functional network indicators and the Wechsler Intelligence Scale score [verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), processing speed index (PSI), full scale intelligence quotient (FSIQ)], disease duration and age of onset was evaluated using a Spearman or Pearson correlation analysis. Results:Compared to the healthy control group, DRE group exhibited decreased VCI, PRI, WMI, PSI, FSIQ and the differences were all statistically significant (all P<0.05). Both brain functional networks had small world attributes. There was a statistically significant difference in the area under the curve of sparsity of degree centrality (DC) in the left pallidum between the DRE group and healthy control group (2.998±0.942, 4.992±1.945, t=-4.07, FDR corrected P<0.05). Compared with the control group, the DRE group had decreased SFC within the limbic network (LN) ( P<0.05), increased SFC within the sensorimotor (SMN) ( P<0.05), decreased SFC between the default mode network-LN ( P<0.05), and increased SFC between the SMN-attentional network (AN) ( P<0.05). There was no statistically significant difference in SFC at the whole brain level between the two groups. Correlation analysis indicated that DC in left pallidum in DRE group negatively correlated with the PSI ( r=-0.537, P=0.018), and SFC between the SMN and AN demonstrated a negative correlation with age of onset ( r=-0.537, P=0.018). Conclusion:The altered DC in left pallidum may be related to cognitive impairment in children with DRE, providing biomarker information for the study of neural mechanisms in children with DRE.