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.

ObjectiveStroke poses a heavy burden due to its high mortality and morbidity rates. Accurate and real-time detection of lesions is pivotal for prompt clinical intervention and favorable prognosis. Electrical impedance tomography (EIT) and microwave tomography (MWT) have emerged as compelling alternatives for stroke screening, owing to their non-ionizing, non-invasive and portable nature. EIT provides information on tissue conductivity, and MWT offers high sensitivity to changes in dielectric properties. However, single-modality imaging is inherently limited, EIT suffers from low sensitivity to deep-seated tissues and severe ill-posedness of inverse problems, whereas MWT is challenged by strong nonlinearity in inverse scattering and susceptibility to modeling errors. Consequently, the clinical utility of standalone EIT or MWT for stroke diagnosis remains constrained by poor spatial resolution and imaging artifacts. To improve the accuracy and robustness of stroke imaging, a dual-modality fusion conditional denoising diffusion probabilistic model (DM-DDPM) was proposed for high-precision dual-modality image reconstruction. MethodsA dual-encoder network with a symmetric architecture and independently trained parameters was constructed to extract heterogeneous features separately from EIT boundary voltage measurements and MWT scattered field signals. Attentional feature fusion (AFF) is employed to integrate complementary information from the two modalities adaptively, generating robust fused priors that suppress redundant noise while preserving key physical characteristics. Subsequently, the fused priors are embedded into a Transformer-based diffusion model via a cross attention mechanism to guide the reverse denoising process. This approach effectively reduces artifacts and enhances the stability of conductivity distribution reconstruction. Time step embedding is introduced to enable the network to perceive the diffusion stage and further improve the accuracy of noise prediction. ResultsSimulated experiments demonstrated that DM-DDPM significantly outperforms single-modality and multi-modality networks under various noise levels. A head model simulation dataset was constructed based on COMSOL Multiphysics, and tests were carried out under 50 dB, 40 dB and 30 dB signal-to-noise ratio levels. At 30 dB, the average relative error (RE) was below 0.20, while the structural similarity index measure (SSIM) and correlation coefficient (CC) remained above 0.90 and 0.89, respectively. Compared with single-modality and multi-modality networks, artifacts were significantly reduced, lesion edges were clearer, and localization was more accurate. The model maintains high reconstruction quality and strong robustness for single, double, and triple lesions simultaneously. Furthermore, physical experiments were conducted using a 16-electrode EIT system and a 16-antenna MWT system with asynchronous data acquisition. These experiments confirmed the feasibility of the method in real-world scenarios and demonstrated that it can robustly reconstruct simulated lesions despite environmental interference and measurement noise, validating its reliability for practical clinical applications. ConclusionThe proposed method effectively combines complementary dual-modality information with a conditional diffusion model. Low accuracy and poor noise resistance in single-modality imaging were effectively addressed, while the noise amplification issue caused by direct multimodal data fusion was avoided. The proposed algorithm exhibits strong anti-noise interference ability and high imaging stability in both simulation and physical experiments. Precise localization of stroke lesions with different quantities was achieved, providing a high-precision, and practical technical support for clinical stroke detection.

Objective In order to understand the current resistance status of Aedes albopictus(Ae. albopictus) adult population to commonly used insecticides and the resistance dynamics development in Zhejiang Province and provide a theoretical basis for the scientific and rational use of hygienic insecticides. Methods Resistance determination was carried out using the diagnostic dose method(GB/T 26347-2010)recommended by WHO in the adult mosquito contact cylinder method to monitor the resistance of Ae. albopictus field populations in 11 cities and districts in Zhejiang Province in 2024. Results The monitoring result showed that adult Ae. albopictus in 11 areas were resistant or suspected resistant populations to both cis-cypermethrin and permethrin; suspected and resistant populations to the organophosphate insecticide malathion were as high as 81.82%; while suspected resistance to the carbamate insecticide residual carbofuran accounted for 45.45%, and the rest of the monitoring sites were sensitive to it. Conclusions The result suggest that the generalized resistance of Ae. albopictus populations to pyrethroids and organophosphorus insecticides in the field in Zhejiang Province needs to be highly emphasized. In future mosquito vector and mosquito-borne disease control, insecticides should be selected based on the resistance monitoring information, while following scientific guidelines for insecticide use.

Circadian rhythm is an endogenous biological clock mechanism that enables organisms to adapt to the earth’s alternation of day and night. It plays a fundamental role in regulating physiological functions and behavioral patterns, such as sleep, feeding, hormone levels and body temperature. By aligning these processes with environmental changes, circadian rhythm plays a pivotal role in maintaining homeostasis and promoting optimal health. However, modern lifestyles, characterized by irregular work schedules and pervasive exposure to artificial light, have disrupted these rhythms for many individuals. Such disruptions have been linked to a variety of health problems, including sleep disorders, metabolic syndromes, cardiovascular diseases, and immune dysfunction, underscoring the critical role of circadian rhythm in human health. Among the numerous systems influenced by circadian rhythm, the skin—a multifunctional organ and the largest by surface area—is particularly noteworthy. As the body’s first line of defense against environmental insults such as UV radiation, pollutants, and pathogens, the skin is highly affected by changes in circadian rhythm. Circadian rhythm regulates multiple skin-related processes, including cyclic changes in cell proliferation, differentiation, and apoptosis, as well as DNA repair mechanisms and antioxidant defenses. For instance, studies have shown that keratinocyte proliferation peaks during the night, coinciding with reduced environmental stress, while DNA repair mechanisms are most active during the day to counteract UV-induced damage. This temporal coordination highlights the critical role of circadian rhythms in preserving skin integrity and function. Beyond maintaining homeostasis, circadian rhythm is also pivotal in the skin’s repair and regeneration processes following injury. Skin regeneration is a complex, multi-stage process involving hemostasis, inflammation, proliferation, and remodeling, all of which are influenced by circadian regulation. Key cellular activities, such as fibroblast migration, keratinocyte activation, and extracellular matrix remodeling, are modulated by the circadian clock, ensuring that repair processes occur with optimal efficiency. Additionally, circadian rhythm regulates the secretion of cytokines and growth factors, which are critical for coordinating cellular communication and orchestrating tissue regeneration. Disruptions to these rhythms can impair the repair process, leading to delayed wound healing, increased scarring, or chronic inflammatory conditions. The aim of this review is to synthesize recent information on the interactions between circadian rhythms and skin physiology, with a particular focus on skin tissue repair and regeneration. Molecular mechanisms of circadian regulation in skin cells, including the role of core clock genes such as Clock, Bmal1, Per and Cry. These genes control the expression of downstream effectors involved in cell cycle regulation, DNA repair, oxidative stress response and inflammatory pathways. By understanding how these mechanisms operate in healthy and diseased states, we can discover new insights into the temporal dynamics of skin regeneration. In addition, by exploring the therapeutic potential of circadian biology in enhancing skin repair and regeneration, strategies such as topical medications that can be applied in a time-limited manner, phototherapy that is synchronized with circadian rhythms, and pharmacological modulation of clock genes are expected to optimize clinical outcomes. Interventions based on the skin’s natural rhythms can provide a personalized and efficient approach to promote skin regeneration and recovery. This review not only introduces the important role of circadian rhythms in skin biology, but also provides a new idea for future innovative therapies and regenerative medicine based on circadian rhythms.

The lesion of the left main coronary artery(LM)itself is one of the challenges of interventional therapy.If the lesion is combined with calcification,the interventional therapy is difficult to operate and extremely risky.This case report presents a 77-year-old elderly male patient.Coronary angiography(CAG)indicated severe stenosis of the LM-left anterior descending(LAD)accompanied by severe calcified bifurcation lesions.After pre-dilation,percutaneous coronary intraluminal shock wave balloon catheter angioplasty(IVL)was applied for treatment.Before IVL treatment,the LM-LAD lesion was subjected to ischemic preconditioning by using an appropriate balloon to fix the pressure and gradually upgrading the balloon dilation time.Later,a Cross-over procedure was performed to implant a single stent,achieving satisfactory results.Among them,the ischemic preconditioning methods for LM lesions can provide reference significance for clinicians.

Gingivectomy and periodontal flap surgery are fundamental periodontal surgeries. Undergraduate students majoring in stomatology must master the basic principles of these two surgical procedures and be familiar with their key operational essentials. This article elaborates on how to conduct standardized fundamental periodontal surgery training step by step, including the significance of the two surgical methods in periodontal therapy, the scheduling and implementation strategies of surgical training, the training essentials, as well as common errors and countermeasures during the training process, providing guidance to improve the standardization of periodontal surgery in China.

Decreased exercise tolerance is a common clinical issue in children with congenital heart disease (CHD), significantly impacting their long-term quality of life and increasing the risk of adverse cardiovascular events.However, due to the complexity of CHD, the diversity of assessment methods, and the limitations in equipment accessibility, standardized protocols for evaluating and intervening in exercise tolerance are still lacking.In order to provide a basis for improving exercise tolerance in children with CHD, the latest domestic and international research on the assessment and intervention of exercise tolerance in children with CHD was systematically summarized.The applicability, advantages, and limitations of existing methods, including cardiopulmonary exercise testing, the 6-minute walk test, and smart wearable devices in clinical practice were discussed.Furthermore, the effectiveness of various intervention strategies (such as exercise training, nutritional management, surgical correction, and pharmacological treatment) in improving exercise tolerance was analyzed.

T cell exhaustion plays an immunosuppressive role in malignant tumors. Continuous tumor antigen stimulation, the presence of suppressive immune cells and cytokines in the tumor microenvironment, the up regulation of inhibitory receptor expression on the surface of T cells, changes in T cell related transcription factors, and metabolites in the tumor microenvironment may lead to T cell exhaustion. Reversing the exhaustion of T cells in tumor patients is a promising strategy for tumor immunotherapy. This article will review the latest research progress on T cell exhaustion status, pathogenesis, reversal methods, and clinical applications in hematological tumors.
Humans ; Hematologic Neoplasms/immunology* ; T-Lymphocytes/immunology* ; Tumor Microenvironment ; Immunotherapy ; T-Cell Exhaustion

OBJECTIVE: To evaluate the efficacy and safety of a hospital-made resuscitation pack, a Chinese medicinal herbal compound formula designed to enhance recovery in post-bronchoscopy patients. METHODS: In this randomized, single-blind, placebo-controlled clinical trial, eligible patients were randomly assigned 1:1 to either the treatment or control groups. The patients in the treatment group applied the resuscitation pack, which contained aromatic compounded Chinese herbs. The patients in the control group applied a hospital-made, single herb placebo pack. Packs were placed on the Tiantu (CV 22) acupuncture point for 4 h as soon as the bronchoscopy finished. Efficacy indicators, such as recovery time, patients' symptoms including nausea and dizziness, and adverse events (AEs) were observed and compared. The outcome indices were evaluated at baseline, 1 and 24 h after the bronchoscopy. Subgroup analysis was further performed by patients' age and depth of sedation. RESULTS: When applying generalized estimating equations (GEE) to evaluate the intensity of post-bronchoscopy nausea and vomiting, the intensity was lower in the treatment group (163 cases) compared with the control group (162 cases; 95% CI: 0.004, 0.099, P=0.03]. Also, significantly lower intensity of nausea was observed in the 60-70 years of age subgroup (95% CI: 0.029, 0.169, P=0.006) and deep sedation subgroup (95% CI: 0.002, 0.124; P=0.04). There was no significant difference in dizziness between two groups by GEE (95% CI: -0.134, 0.297; P=0.459). In addition, no serious AEs were observed in either group. CONCLUSIONS Our study found that the resuscitation pack markedly improved patients' symptoms by reducing nausea and vomiting after bronchoscopy without AEs, compared with placebo in the perioperative period. (Trial registration No. ChiCTR2000038299).
Humans ; Male ; Middle Aged ; Female ; Bronchoscopy/adverse effects* ; Single-Blind Method ; Aged ; Drugs, Chinese Herbal/adverse effects* ; Treatment Outcome ; Resuscitation ; Adult ; Medicine, Chinese Traditional

Neuroinflammatory responses play an important role in the pathogenesis of various diseases, particularly those affecting the central nervous system. Inhibition of neuroinflammation is a crucial therapeutic strategy for the management of central nervous system disorders. The intestinal microbial-gut-brain axis serves as a key regulatory pathway that modulates neuroinflammatory processes. Intestinal flora metabolites such as short-chain fatty acids, indoles and their derivatives, lipopolysaccharides, trimethylamine oxide, and secondary bile acids exert direct or indirect effects on neuroinflammation. Studies have shown that electroacupuncture (EA) modulates the composition of the intestinal microbiota and its metabolites, while also suppressing neuroinflammation by targeting the TLR4/NF- κ B, NLRP3/caspase-1, and microglial cell M2-type transformation pathways. This review discusses the mechanisms by which EA regulates neuroinflammation via intestinal microbiota and its metabolites, providing information and a foundation for further investigation of the precise therapeutic mechanisms of EA in neurological disorders.
Humans ; Gastrointestinal Microbiome ; Electroacupuncture ; Neuroinflammatory Diseases/metabolism* ; Animals