1.The Role of FASN in Tumors and Its Targeted Therapy
Wen-Jing JIANG ; Ruo-Xi ZHANG ; Yu-Qing TAI ; Ya-Wen SUN ; Xi-Yu ZHANG ; Xiao LI
Progress in Biochemistry and Biophysics 2026;53(4):920-935
Malignant tumors represent a major threat to global health. Conventional anti-tumor pharmacotherapy often encounters challenges such as drug resistance, highlighting an urgent need for the development of novel therapeutic strategies. Fatty acid synthase (FASN), the key enzyme catalyzing de novo fatty acid synthesis, is subject to precise regulation at multiple levels, including transcriptional control, various post-translational modifications such as ubiquitination and phosphorylation, as well as modulation by diverse signaling pathways. Recent studies have revealed that FASN is aberrantly overexpressed in various malignant tumors and is closely associated with tumor progression and poor patient prognosis. FASN is a homodimer composed of seven functional domains that catalyzes the NADPH-dependent condensation of acetyl-CoA and malonyl-CoA to generate saturated fatty acids, primarily palmitic acid. Its stability is regulated by multiple ubiquitin ligases and deubiquitinating enzymes. Additionally, FASN is subject to upstream regulation via neural precursor cell-expressed developmentally downregulated 8 (Nedd8) modification and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway, thereby establishing a metabolic-signaling positive feedback loop. As a core executor of metabolic reprogramming, FASN promotes tumorigenesis through dual mechanisms. First, its fatty acid synthesis product, palmitate, participates in membrane phospholipid synthesis, lipid raft formation, and protein palmitoylation, thereby activating several key oncogenic signaling pathways, including PI3K/AKT/mTOR, wingless-type MMTV integration site family member (Wnt)/β‑catenin, and signal transducer and activator of transcription 3 (STAT3)/matrix metalloproteinase (MMP), leading to tumor development and progression. Second, FASN plays a pivotal role in modulating the anti-tumor functions of immune cells and remodeling the tumor immune microenvironment. Specifically, FASN enhances immune checkpoint inhibition by inducing programmed death-ligand 1 (PD-L1) palmitoylation, suppresses the activation of cytotoxic T lymphocytes and natural killer cells, and promotes the polarization of M2-type macrophages, consequently facilitating tumor immune evasion and malignant progression. Precisely due to its significant overexpression in tumor cells, its critical functional role, and its differential expression compared to normal cells, FASN has emerged as a highly promising target for anti-tumor drug development. Highly selective small-molecule inhibitors, notably represented by TVB-2640, have advanced to clinical trial stages and demonstrated favorable anti-tumor activity. Furthermore, the combination of FASN inhibitors with other chemotherapeutic agents or targeted drugs can overcome the limitations of monotherapy through synergistic effects or by resensitizing tumor cells to conventional drugs, achieving a “1+1>2” therapeutic outcome. With the advancement of modern traditional Chinese medicine (TCM), numerous active ingredients derived from TCM have been confirmed to exert anti-tumor effects by modulating FASN-related pathways. This integrated approach leverages the precision of Western medicine while simultaneously harnessing the holistic regulatory benefits of TCM to alleviate the side effects of radiotherapy and chemotherapy. Despite the promising prospects of FASN-targeted therapies, challenges remain, including tumor cell metabolic plasticity, tumor context-dependent responses, and heterogeneity. This review systematically summarizes the molecular structure, physiological functions, and mechanisms of FASN in tumorigenesis, as well as recent advances in targeted therapies. Future directions—including the precise identification of responsive patient populations using spatial transcriptomics, the development of novel combination regimens, and the active exploration of integrative strategies combining traditional Chinese and Western medicine—will facilitate the clinical translation of FASN-targeted therapies and open new avenues for improving the quality of life and prognosis of cancer patients.
2.An Attention-weighted Tri-modal Ultrasound Network (TUS-Net) for Screening of Atypical Hepatocellular Carcinoma From LR-M Liver Nodules
He-Chong ZHANG ; Liang-Hui HUANG ; Xue-Hua WANG ; Shang-Lin JIANG ; Ying-Ying CHEN ; Ya-Guang ZENG ; Wei ZHENG
Progress in Biochemistry and Biophysics 2026;53(5):1485-1498
ObjectiveDiscriminating atypical hepatocellular carcinoma (HCC) from other malignancies in liver nodules classified as Liver Imaging Reporting and Data System category M (LR-M) remains a significant diagnostic challenge on conventional ultrasound examination. The LR-M category, originally intended to capture non-HCC malignancies, paradoxically contains up to 63% of atypical HCCs that deviate from classic enhancement patterns, leading to potential misdiagnosis and suboptimal treatment planning. While deep learning has shown promise in HCC diagnosis, most existing models rely exclusively on single-modality ultrasound, overlooking the diagnostic benefits of integrating complementary information from multiple imaging sources. To address this gap, we propose a novel attention-weighted tri-modal ultrasound network (TUS-Net) that integrates contrast-enhanced ultrasound (CEUS), B-mode ultrasound (BUS), and time-intensity curves (TICs) to improve diagnostic accuracy for these clinically challenging lesions. MethodsOur framework incorporates a three-dimensional convolutional neural network (C3D) backbone to extract spatiotemporal features from CEUS videos, capturing dynamic vascular patterns critical for lesion characterization. To effectively fuse complementary modalities, we introduce a dual-channel feature fusion module (DCFFM) that adaptively combines features from CEUS and BUS through channel-wise attention mechanisms, allowing the model to dynamically weigh the contribution of each modality based on diagnostic relevance. Additionally, we propose a temporal intensity feature fusion module (TIFFM) that leverages quantitative hemodynamic information from TICs to guide the model’s attention toward diagnostically critical temporal phases, such as arterial wash-in and portal venous washout. The model is further enhanced by automated lesion localization using YOLOX and class activation mapping for interpretability, ensuring that predictions align with clinically meaningful imaging features. ResultsEvaluated on a tri-modal ultrasound dataset comprising 161 patients with pathologically confirmed LR-M nodules (131 atypical HCC and 30 non-HCC malignancies), our model achieved an accuracy of 86.83%, a sensitivity of 92.50%, a specificity of 75.50%, and an AUC of 89.32% in screening atypical HCC. Compared to single-modality baselines, TUS-Net demonstrated superior specificity, a clinically critical metric given the higher risk associated with misclassifying non-HCC malignancies. Ablation studies confirmed the contribution of each module, with the full model outperforming both standard C3D and 3D ResNet backbones integrated with attention mechanisms. A reader study involving junior and senior radiologists further validated the clinical utility of AI assistance, showing consistent improvements in specificity and inter-reader consistency, particularly for less experienced clinicians. ConclusionThese results surpass existing benchmark models and demonstrate the potential of our approach to enhance diagnostic precision in clinically specific cases. By intelligently fusing multi-modal ultrasound data with attention-guided mechanisms, TUS-Net offers a reliable and interpretable tool that holds promise for improving the non-invasive diagnosis of atypical HCC in challenging LR-M liver nodules.
3.An Attention-weighted Tri-modal Ultrasound Network (TUS-Net) for Screening of Atypical Hepatocellular Carcinoma From LR-M Liver Nodules
He-Chong ZHANG ; Liang-Hui HUANG ; Xue-Hua WANG ; Shang-Lin JIANG ; Ying-Ying CHEN ; Ya-Guang ZENG ; Wei ZHENG
Progress in Biochemistry and Biophysics 2026;53(5):1485-1498
ObjectiveDiscriminating atypical hepatocellular carcinoma (HCC) from other malignancies in liver nodules classified as Liver Imaging Reporting and Data System category M (LR-M) remains a significant diagnostic challenge on conventional ultrasound examination. The LR-M category, originally intended to capture non-HCC malignancies, paradoxically contains up to 63% of atypical HCCs that deviate from classic enhancement patterns, leading to potential misdiagnosis and suboptimal treatment planning. While deep learning has shown promise in HCC diagnosis, most existing models rely exclusively on single-modality ultrasound, overlooking the diagnostic benefits of integrating complementary information from multiple imaging sources. To address this gap, we propose a novel attention-weighted tri-modal ultrasound network (TUS-Net) that integrates contrast-enhanced ultrasound (CEUS), B-mode ultrasound (BUS), and time-intensity curves (TICs) to improve diagnostic accuracy for these clinically challenging lesions. MethodsOur framework incorporates a three-dimensional convolutional neural network (C3D) backbone to extract spatiotemporal features from CEUS videos, capturing dynamic vascular patterns critical for lesion characterization. To effectively fuse complementary modalities, we introduce a dual-channel feature fusion module (DCFFM) that adaptively combines features from CEUS and BUS through channel-wise attention mechanisms, allowing the model to dynamically weigh the contribution of each modality based on diagnostic relevance. Additionally, we propose a temporal intensity feature fusion module (TIFFM) that leverages quantitative hemodynamic information from TICs to guide the model’s attention toward diagnostically critical temporal phases, such as arterial wash-in and portal venous washout. The model is further enhanced by automated lesion localization using YOLOX and class activation mapping for interpretability, ensuring that predictions align with clinically meaningful imaging features. ResultsEvaluated on a tri-modal ultrasound dataset comprising 161 patients with pathologically confirmed LR-M nodules (131 atypical HCC and 30 non-HCC malignancies), our model achieved an accuracy of 86.83%, a sensitivity of 92.50%, a specificity of 75.50%, and an AUC of 89.32% in screening atypical HCC. Compared to single-modality baselines, TUS-Net demonstrated superior specificity, a clinically critical metric given the higher risk associated with misclassifying non-HCC malignancies. Ablation studies confirmed the contribution of each module, with the full model outperforming both standard C3D and 3D ResNet backbones integrated with attention mechanisms. A reader study involving junior and senior radiologists further validated the clinical utility of AI assistance, showing consistent improvements in specificity and inter-reader consistency, particularly for less experienced clinicians. ConclusionThese results surpass existing benchmark models and demonstrate the potential of our approach to enhance diagnostic precision in clinically specific cases. By intelligently fusing multi-modal ultrasound data with attention-guided mechanisms, TUS-Net offers a reliable and interpretable tool that holds promise for improving the non-invasive diagnosis of atypical HCC in challenging LR-M liver nodules.
4.Serpina3c Mitigates Adipose Tissue Inflammation by Inhibiting the HIF1α-Mediated Endoplasmic Reticulum Overoxidation in Adipocytes
Yu JIANG ; Jia-Qi GUO ; Ya WU ; Peng ZHENG ; Shao-Fan WANG ; Meng-Chen YANG ; Gen-Shan MA ; Yu-Yu YAO
Diabetes & Metabolism Journal 2026;50(1):62-76
Background:
Visceral white adipose tissue (vWAT) inflammation is a critical pathology of obesity-caused heart damage and is closely associated with adipocyte endoplasmic reticulum (ER) dysfunction. Serine (or cysteine) peptidase inhibitor, clade A, member 3C (Serpina3c) has been identified as an adipokine with anti-vWAT inflammatory effects. However, it remains unclear whether Serpina3c deficiency promotion of vWAT inflammation involves adipocyte ER dysfunction and whether it further contributes to heart damage in obesity.
Methods:
Wild type and Serpina3c knockout (Serpina3c–/–) mice were fed a high-fat diet (HFD) for 12 weeks. An adeno-associated virus (AAV) was injected locally into epididymal white adipose tissue (eWAT) of Serpina3c–/– mice to induce eWAT-adipocyte- specific overexpression of Serpina3c (AAV-Serpina3c) or knockdown of hypoxia-inducible factor 1α (AAV-shHIF1α). In vitro experiments were performed in 3T3-L1 adipocytes.
Results:
Serpina3c–/– mice exhibited more severe eWAT, serum and heart inflammation after HFD feeding. Consistently, these adverse phenotypes were mitigated in AAV-Serpina3c and AAV-shHIF1α mice. Mechanistically, ER oxidoreductase 1α (Ero1α) and protein disulfide isomerase (PDI) family members PDIA3 and PDIA4 were found to be target genes of HIF1α. In the obese mice, Serpina3c deficiency caused adipocyte more hypertrophy, and activated HIF1α-Ero1α/PDI mediated ER overoxidation and ER stress in eWAT. Subsequently, this led to increased adipocyte apoptosis and chemokine production and decreased adiponectin expression, which promoted macrophage infiltration and M1 polarization in eWAT, thus exacerbating eWAT inflammation and ultimately facilitating serum and distal heart inflammation.
Conclusion
These findings indicate that Serpina3c is a significant regulator of adipocyte ER redox homeostasis, thus highlighting Serpina3c as a potential therapeutic target for obesity-related eWAT inflammation and heart damage.
5.Analysis of soil-borne nematode infection status among rural communities in Yubei, Chongqing
Dan JIANG ; Yong-dong HAO ; Sen-ping YANG ; Xiao-yuan SU ; Hua-jun BAI ; Bo LYU ; Ya-ling RAN ; He-yi GUAN ; Ling HU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):85-89
Objective To analyze the infection status and epidemic trends of soil-borne nematode infections in Yubei, Chongqing City, in 2010,2021, and 2022. Methods The local populations from four survey sites of four towns in 2010 and five sites of five towns in 2021 and 2022 were surveyed regarding their basic information using a unified form. Fecal samples of the participants were collected and tested for soil-borne nematode infections using the modified Kato-Katz thick smear method. Results In 2010, 2 049 participants were surveyed, followed by 1 000 participants in 2021 and 2022. The overall prevalence of parasitic infections declined significantly from 3.86% to 0.20%. In 2010, soil-transmitted nematode included hookworms(3.81%) and roundworms(0.29%). In 2021, the infection rates of roundworms and hookworms were 1.70% and 0.10% respectively. Notably, only Ascaris was identified in 2022(0.20%). The≥60 age group consistently exhibited the highest infection rates across all surveys, followed by the 40-59 age group. The infection rates of males in the three surveys were 3.31%,1.92%, and 0.20% respectively, and those of females were 4.37%, 1.46%, and 0.20% respectively. There was no statistically significant difference in the infection rates between males and females. Educational attainment was inversely associated with infection; in 2010, the highest prevalence was observed among those with primary education or below, whereas in 2021, illiterate or semi-literate individuals showed the highest susceptibility. The occupational distribution of infections in 2010 indicated that retirees (8.33%), farmers(4.86%), and homemakers or unemployed individuals(3.45%)were the most affected. However, in 2021 and 2022, farmers emerged as the predominant occupational group with soil-transmitted nematode infections. Conclusions The infection rate of soil-borne nematodes showed a decreasing trend in Yubei, and the infection species changed from hookworms in 2010 to Ascaris in 2022. Farmers, the elderly, and people with low education levels should continue to be the focus of preventive and control efforts.
6.A new species of Culicoides (Avaritia) (Diptera: Ceratopogonidae) in Heilongjiang Province, China
Ya-yu WANG ; Jiang-fan LI ; Bo-qiao CAI ; Guo-ping LIU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(1):62-65
This study reports a new species of Culicoides(Avaritia)isolated from Xunke County, Heilongjiang Province, China. The new species, Culicoides(Avaritia)dongshanensis Liu et Wang, sp. nov., was identified and illustrated based on female adults. Its diagnostic characteristics are as follows: eyes contiguous over a short distance, with short interfacetal hair, antennal ratio(AR)of 1.20, palpal ratio(PR)of 2.16, wing length of 0.83 mm, mandible with 15 teeth, one pale spot in base cell M1, one pale spot in cell M4, two pale spots in cell A, and two unequal spermathecae. Type specimens were deposited at the Center for Disease Control and Prevention of the Northern Theater Command.
7.Expert consensus on electronic patient-reported outcome-based symptom management for perioperative lung cancer patients (version 2026)
Wei DAI ; Cheng LEI ; Yuanqiang ZHANG ; Rong ZHANG ; Pengyu Jinming ; Jinming XU ; Yuzhen ZHENG ; Liang ZHAO ; Guibin QIAO ; Guowei CHE ; Jian HU ; Lei JIANG ; Jie LI ; Qiang LI ; Qiuling SHI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(08):1166-1178
Patients with lung cancer experience a heavy symptom burden during the perioperative period, which seriously affects their recovery and quality of life. Traditional symptom management models rely mainly on scheduled ward rounds during hospitalization and outpatient follow-up after discharge. However, they have limitations such as delayed symptom recognition, lack of post-discharge monitoring, and non-quantitative symptom assessment, which often lead to delayed interventions and low patient satisfaction. In recent years, the symptom management model based on electronic patient-reported outcomes (ePRO) has been increasingly valued in clinical practice. Existing high-level evidence from both domestic and international studies indicates that, through proactive monitoring, real-time alerts, and remote interventions, this model enables dynamic and continuous symptom management and helps improve patient recovery and healthcare experience. As a supplement to routine medical care, the ePRO-based symptom management model aims to enhance the quality of care rather than replace existing medical processes. To promote the standardized application of this model in perioperative lung cancer care, this consensus integrates domestic and international evidence. After multiple rounds of voting by more than 50 experts, it formulates 12 consensus statements covering the three core components, symptom monitoring, alerting, and intervention, to provide scientific and practical recommendations for clinical practice.
8.Effect of salidroside combined with rosavin on ischemic brain injury in rats
Wen-fang LAI ; Yu-ting JIANG ; Jing-quan CHEN ; Xue-rui ZHENG ; Hui-ling WU ; Qing-qing WU ; Yan CHEN ; Ya LIN
Chinese Pharmacological Bulletin 2025;41(11):2058-2065
Aim To study the mechanism of salidro-side combined with rosavin in rats with ischemic stroke.Methods The MCAO rats was established by using thread-embolic method.The rats were divided into the sham group,MCAO group,salidroside com-bined with rosavin group,and positive control group;the drug was given continuously for seven days.Western blot was used to detect apoptosis indicators.Proteomics was used to analyse differential proteins(DEPs).STEP receptor inhibitor was injected into the lateral ventricles,the rats were administered for seven days,then the apoptosis indicators were detected.Re-sults Salidroside combined with rosavin could reduce neurological function scores in MCAO rats and inhibit cell apoptosis.Quantitative proteomics identified 496 DEPs in brain tissue and discovered core proteins STEP,p38,and CRTC1.Salidroside combined with rosavin could promote the STEP and CRTC1 while in-hibiting p38 protein.After treatment with STEP inhibi-tor,those effects were reversed.Conclusion Salidro-side combined with rosavin can inhibit cell apoptosis in MCAO rats,which is closely related to the regulation of the STEP/p38/CRTC1 signaling pathway.
9.The effects of fluoride and aluminum exposure alone and in combination on pyroptosis and NLRP3/Caspase-1/ GSDMD signaling pathway in NG108-15 cells
Ya XIA ; Hongshuang JIANG ; Xiaoling QIAN ; Chun XIE
Chinese Journal of Endemiology 2025;44(4):272-278
Objective:To study the effects of fluoride and aluminum exposure alone and in combination on pyroptosis and the NOD-like receptor protein 3 (NLRP3)/cysteinyl aspartate specific proteinase-1 (Caspase-1)/gasdermin D (GSDMD) signaling pathway in NG108-15 cells.Methods:Using a factorial design method, NG108-15 cells cultured in vitro were divided into control group [0 mg/L sodium fluoride (NaF) + 0 mg/L aluminium trichloride (AlCl 3)], fluoride group (40 mg/L NaF + 0 mg/L AlCl 3), aluminum group (0 mg/L NaF + 160 mg/L AlCl 3), and fluoride + aluminum group (40 mg/L NaF + 160 mg/L AlCl 3) according to the concentrations of NaF and AlCl 3. After 24 hours of cultivation, the cells were collected for subsequent experiments. The fluorescence intensity of pyroptosis index GSDMD in each group was detected by immunofluorescence method. The mRNA expression levels of NLRP3, apoptosis associated speck-like protein (ASC), Caspase-1, and GSDMD in each group were detected by real-time fluorescence quantitative PCR (qRT-PCR). The protein expression levels of NLRP3, ASC, Caspase-1, GSDMD, gasdermin D N-terminus (GSDMD-N) and interleukin-1β (IL-1β) in each group were detected by Western blotting. Results:The immunofluorescence results showed that compared with the control group (1.00 ± 0.02), the fluorescence intensity of GSDMD in the fluoride, aluminum, and fluoride + aluminum groups (1.49 ± 0.02, 1.22 ± 0.04, 1.25 ± 0.03) were higher ( P < 0.05). The results of qRT-PCR showed that compared with the control group (1.00 ± 0.02, 1.00 ± 0.01, 1.00 ± 0.08, 1.00 ± 0.06), the mRNA expression levels of NLRP3 (1.21 ± 0.06, 1.60 ± 0.07, 1.42 ± 0.02), ASC (2.61 ± 0.07, 1.53 ± 0.01, 2.12 ± 0.03), Caspase-1 (1.32 ± 0.05, 1.53 ± 0.04, 2.07 ± 0.05), and GSDMD (1.60 ± 0.03, 1.65 ± 0.04, 2.23 ± 0.05) were higher in the fluoride, aluminum, and fluoride + aluminum groups ( P < 0.05). Western blotting results showed that compared with the control group (1.00 ± 0.04, 1.00 ± 0.08, 1.00 ± 0.05, 1.00 ± 0.02, 1.00 ± 0.03, 1.00 ± 0.06), the protein expression levels of NLRP3 (1.55 ± 0.06, 1.40 ± 0.07, 1.24 ± 0.05), ASC (1.66 ± 0.05, 1.48 ± 0.06, 1.32 ± 0.06), Caspase-1 (1.51 ± 0.02, 1.40 ± 0.01, 1.28 ± 0.03), GSDMD (1.24 ± 0.03, 1.31 ± 0.06, 1.18 ± 0.03), GSDMD-N (1.18 ± 0.04, 1.27 ± 0.03, 1.27 ± 0.03), and IL-1β (1.81 ± 0.03, 1.70 ± 0.08, 1.52 ± 0.05) were higher in the fluoride, aluminum, and fluoride + aluminum groups ( P < 0.05). Conclusion:Exposure to fluoride and aluminum alone and in combination can induce pyroptosis in NG108-15 cells, and the mechanism may be related to up-regulation of molecules related to the NLRP3/Caspase-1/GSDMD signaling pathway.
10.Event-related potential study on cognitive function in children with obstructive sleep apnea
Ya ZHANG ; Yunxiao WU ; Yingchao JIANG ; Li ZHENG ; Zhifei XU
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(4):334-339
Objective:To investigate the changes in N100, P300, and N400 of event-related potential(ERP) in children with obstructive sleep apnea (OSA), and provide the basis for evaluating cognitive and neurological impairment in pediatric OSA.Methods:Totally 108 children aged 5-10 years who visited the Sleep Center of Beijing Children's Hospital due to snoring or mouth breathing were recruited from June to September, 2023, and ultimately 90 children were included in the study.According to the obstructive sleep apnea hypopnea index (OAHI) in their polysomnography (PSG) results, children with OAHI>1 time/h were classified as OSA group ( n=74), and children with OAHI ≤ 1 time/h were classified as non-OSA group ( n=16).All participants completed the auditory oddball and Peabody image vocabulary test tasks, and the EEG data collected through ERP technology were compared between the two groups.SPSS 26.0 software was used for statistical analysis, and independent samples t-test or non parametric test was used for comparison between the two groups. Results:The P300 latency of OSA children in lead Fz was significantly longer than that of non OSA children (330.00(308.00, 396.00) ms, 309.00(294.50, 337.50)ms), and the difference was statistically significant ( Z=-2.143, P=0.032). The latency of P300 was positively correlated with apnea hypopnea index(AHI)(Fz lead: r=0.332, Cz lead: r=0.239, Pz lead: r=0.213, all P<0.05). There was no statistically significant difference in P300 latency between Cz and Pz leads ( Z=-1.615, P=0.106; Z=-1.055, P=0.291). There was no statistically significant difference in the amplitude of P300 among the leads (all P>0.05). There was no statistically significant difference in the amplitude and latency of N100 and N400 (both P>0.05). Conclusion:The latency of P300 in OSA children is significantly longer than that in non-OSA children, indicating impaired cognitive function. The latency of auditory P300 might serve as an early neuroelectrophysiological biomarker for identifying cognitive impairment in OSA children.


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