1.α-ketoglutarate ameliorated arsenic-induced hepatic lipid deposition in offspring via PI3K/AKT signaling pathway
Shuangrui BAO ; Hongyan WU ; Ying SUN ; Tong ZHAN ; Qian YANG ; Xinru LIANG ; Zhiyan WAN ; Wenyi CHEN ; Cheng ZHANG
Acta Universitatis Medicinalis Anhui 2026;61(2):225-231
ObjectiveTo investigate the protective effect of α-ketoglutarate (α-KG) on hepatic lipid deposition in offspring caused by arsenic exposure during pregnancy. Methods8-week-old institute of cancer research (ICR) mice were mated in a ratio of 2∶1 between females and males, and the detection of vaginal plugs confirmed pregnant. A total of 32 pregnant mice were randomly divided into four groups: control group, arsenic group, α-KG group, arsenic+α-KG group. On gestational day 0-16 (GD0-GD16), the arsenic and arsenic+α-KG groups were exposed to sodium arsenite (NaAsO2 ,15 mg/L) in drinking water everyday, and the α-KG and arsenic+α-KG groups were gavaged with α-KG (2 g/kg) everyday. On GD16, pregnant mice were euthanized to collect fetal liver, and fetal body weight and crown-rump length were measured. Gene expression differences between the control group and the arsenic group were analyzed by transcriptome. The total triglycerides (TGs) and subtypes in fetal liver were detected by liquid chromatography tandem mass spectrometry (LC-MS/MS). Oil red O staining was used to observe the histopathological changes in the liver. Quantitative polymerase chain reaction (qPCR) was used to detect the expression level of genes related to lipid synthesis, transport, and degradation, and phosphatidylinositol 3' -kinase/ protein kinase B (PI3K/AKT) in the liver of fetus. ResultsTranscriptomics analysis showed that 2 144 genes were downregulated and 1 675 genes were upregulated in the arsenic exposed fetal liver; body weight and crown-rump length were reduced (PTuKey<0.05); the level of hepatic TGs was elevated in arsenic group (PTuKey<0.05); oil-red O staining showed a significant increase in lipid droplets in arsenic group (PTuKey<0.01); the expression of lipid synthesis-related genes were significantly upregulated (PTuKey<0.05); the expression of β-oxidation-related genes and lipid degradation-related genes were downregulated (PTuKey<0.05); the expression of PI3K, AKT decreased(PTuKey<0.05). Compared with the arsenic group, the body weight and crown-rump length of fetus increased in the arsenic+α-KG group (PTuKey<0.05); the level of hepatic TGs decreased in the arsenic+α-KG group (PTuKey<0.05); oil red O staining showed lipid droplets significantly decreased (PTuKey<0.01); the expression of lipid synthesis-related genes were downregulated (PTuKey<0.05), the expression of β-oxidation-related genes and lipid degradation-related genes were upregulated (PTuKey<0.05); the expression levels of PI3K and AKT increased (PTuKey<0.05). Conclusionα-KG alleviated hepatic lipid deposition in offspring exposed to arsenic during pregnancy through activating PI3K/AKT signaling pathway.
2.Association of liver fibrosis markers and inflammation markers with the risk of gallstones in patients with metabolic dysfunction-associated fatty liver disease
Shuai ZHANG ; Shoulu JIN ; Wanqing LI ; Xijing SHI ; Hao LIANG ; Hao DONG ; Dailong LU ; Ying ZHU ; Xiaoxing XIANG ; Jun LIU
Journal of Clinical Hepatology 2026;42(3):579-585
ObjectiveTo investigate the association of liver fibrosis scores and inflammation markers with gallstones in patients with metabolic dysfunction-associated fatty liver disease (MAFLD), as well as the mediating role of liver fibrosis scores in the relationship between inflammation markers and gallstones. MethodsA total of 14 567 patients who received physical examination and were diagnosed with MAFLD in Subei People’s Hospital from January 2014 to June 2023 were enrolled in this study, and according to the results of abdominal color Doppler ultrasound, they were divided into gallstone group with 1 724 patients and non-gallstone group with 12 843 patients. Related clinical data were collected from all patients, including demographic data, medical history, family history, physical examination, Color Doppler ultrasound, and biochemical parameters. The biomarkers associated with metabolic disorders and insulin resistance included triglyceride-glucose index (TyG), TyG-body mass index (BMI) index, atherogenic index of plasma (AIP), and non-high-density lipoprotein cholesterol-to-high-density lipoprotein cholesterol ratio (NHHR); the biomarkers associated with inflammation and nutritional status included neutrophil-to-lymphocyte ratio (NLR), neutrophil percentage-to-albumin ratio (NPAR), and monocyte-to-lymphocyte ratio (MLR); the biomarkers for assessing liver fibrosis degree and liver function included albumin-bilirubin (ALBI) score, NAFLD fibrosis score (NFS), fibrosis-4 (FIB-4) index, and aspartate aminotransferase-to-platelet ratio index (APRI). The independent-samples t test was used for comparison of normally distributed continuous data between two groups, while the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. Multivariate Logistic regression analysis, restricted cubic spline analysis, and mediating effect analysis were used to assess the association of liver fibrosis markers and inflammation markers with the risk of gallstones. ResultsThe prevalence rate of gallstones was 11.8% among the MAFLD patients. There were significant differences between the gallstone group and the non-gallstone group in sex, age, smoking history, diabetes, hypertension, lymphocytes, platelets, glucose, albumin, serum uric acid, alanine aminotransferase, aspartate aminotransferase, red blood cell, NLR, NPAR, MLR, NFS, FIB-4 index, and ALBI score (all P<0.05). The multivariate Logistic regression analysis showed that NLR (odds ratio [OR]=1.091, 95% confidence interval [CI]: 1.028 — 1.160, P<0.05), NPAR (OR=1.073, 95%CI: 1.042 — 1.105, P<0.05), MLR (OR=1.142, 95%CI: 1.057 — 1.232, P<0.05), NFS (OR=1.239, 95%CI: 1.190 — 1.291, P<0.05), and FIB-4 index (OR=1.326, 95%CI: 1.241 — 1.417, P<0.05) were influencing factors for the prevalence rate of gallstones. The restricted cubic spline analysis showed a significant non-linear association between NFS/FIB-4 index and the risk of gallstone (non-linear P<0.05). The mediating effect analysis further showed that the association of NLR, MLR, and NPAR with gallstones was partially mediated by NFS or FIB-4 index, with a mediating effect accounting for 36.79%、28.09%、29.67% and 18.31%、17.70、11.57%, respectively. ConclusionNFS and FIB-4 index have a non-linear association with the prevalence rate of gallstones in MAFLD patients, and they also mediate the association of NLR, NPAR, and MLR with the risk of gallstone.
3.Role of aspirin in metabolic associated fatty liver disease
Yongqi LI ; Yanqiu LI ; Lina SUN ; Chaoran WANG ; Ying FENG ; Liang WANG ; Xianbo WANG
Journal of Clinical Hepatology 2026;42(1):178-182
Metabolic associated fatty liver disease (MAFLD) is the main type of chronic liver disease in the world, with an increasingly higher incidence rate and a younger age of onset. At present, the treatment of MAFLD mainly depends on lifestyle intervention and comorbidity management, and there is still a lack of effective drugs for MAFLD itself. As a classic nonsteroidal anti-inflammatory drug of the salicylic acid family, aspirin can intervene in the pathological process of MAFLD by regulating lipid metabolism, relieving insulin resistance, reducing liver inflammation and oxidative stress response, exerting an anti-liver fibrosis effect, and inhibiting hepatocellular carcinoma, and therefore, it has the value of preventing disease onset, delaying disease progression, and reversing disease condition. This article systematically reviews the mechanism of action and safety of aspirin in the treatment of MAFLD, in order to provide more drug treatment options for MAFLD patients.
4.Correlation between liver fibrosis degree and carotid plaque in patients with lean metabolic dysfunction-associated fatty liver disease
Shuai ZHANG ; Shoulu JIN ; Wanqing LI ; Xijing SHI ; Hao LIANG ; Hao DONG ; Dailong LU ; Ying ZHU ; Xiaoxing XIANG ; Jun LIU
Journal of Clinical Hepatology 2026;42(2):319-325
ObjectiveTo investigate the association between noninvasive liver fibrosis markers and carotid plaque (CP) in patients with lean metabolic dysfunction-associated fatty liver disease (MAFLD), and to provide a basis for screening high-risk populations. MethodsA total of 957 patients with lean MAFLD who underwent physical examination in Subei People’s Hospital from January 2021 to June 2023 was enrolled as the observation cohort, with the presence or absence of CP as the outcome, and fibrosis-4 (FIB-4) index and nonalcoholic fatty liver disease fibrosis score (NFS) were used to assess liver fibrosis degree. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. The multivariate logistic regression analysis, the restricted cubic spline analysis, the receiver operating characteristic curve, and the mediation effect analysis were used to investigate the association between liver fibrosis degree and CP. ResultsThe prevalence rate of CP was 36.6% in the lean MAFLD population. Compared with the non-CP group(n=607), the CP group (n=350) had a significantly higher proportion of male patients, a significantly higher proportion of patients with smoking/diabetes/hypertension, and significantly higher levels of age, creatinine, blood urea nitrogen, triglycerides, fasting blood glucose, aspartate aminotransferase, aspartate aminotransferase/alanine aminotransferase ratio, NFS, and FIB-4 index, as well as significantly lower levels of platelet count and albumin (all P<0.05). The multivariate logistic regression analysis showed that after adjustment for confounding factors, FIB-4 index (odds ratio[OR]=2.979, 95% confidence interval[CI]:2.141 — 4.219, P<0.001) and NFS (OR=1.747, 95%CI: 1.499 — 2.046, P<0.001) were positively correlated with CP. Both FIB-4 index and NFS had a good value in predicting CP. Hypertension had a significant indirect effect on the prevalence rate of CP through its impact on liver fibrosis markers, and its mediating effect accounted for 39.5% — 40.8% of the total effect (P<0.001). ConclusionIn patients with lean MAFLD, NFS and FIB-4 index are significantly positively correlated with the prevalence rate of CP, and they can be used as potential epidemiological predictive indicators. Liver fibrosis markers may play a mediating role in the association between hypertension and CP. Interventions targeting hypertension and liver fibrosis markers may help to prevent and delay the progression of CP.
5.Expert consensus on clinical application of parenteral direct thrombin inhibitors in perioperative period
Mingyu JIANG ; Yuan BIAN ; Lizhu HAN ; Qinan YIN ; Fengjiao KANG ; Anhua WEI ; Danjie ZHAO ; Lin WANG ; Ying SHAO ; Li TANG ; Yi WANG ; Shuhong LIANG ; Huijuan LIU ; Guirong XIAO ; Yue LI
China Pharmacy 2026;37(6):689-699
OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors (DTIs) in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital (the Affiliated Hospital of UESTC), a multidisciplinary working group was established. Through literature review and the Delphi method, clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework; systematic searches were conducted in CNKI, Medline, Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment,Development and Evaluation (GRADE) approach, and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations (each with an expert consensus rate exceeding 90%) on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection, dosing ranges, key monitoring points, and safety management strategies for parenteral DTIs in various scenarios, including the perioperative period of ventricular assist device implantation, the perioperative period of cardiac surgery, perioperative patients with lower-extremity atherosclerotic disease, the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome, the perioperative period of carotid artery stenting in patients with carotid stenosis, the perioperative period of patients with right heart thrombosis, and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition, warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus, which is formulated based on the best available evidence, provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.
6.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.
7.Comparison of professional competency between full-time and part-time personnel of the nosocomial infection control administration in Shanghai
Jin WANG ; Liang ZHANG ; Ying LYU ; Kun ZHANG ; Yanting WANG ; Xiaodong GAO ; Qingfeng SHI ; Yizhou JIANG
Shanghai Journal of Preventive Medicine 2026;38(3):245-250
ObjectiveTo investigate the current professional competency among full-time and part-time personnel of the nosocomial infection control administration in Shanghai, so as to provide a scientific basis for future training programmes. MethodsIn December 2024, a questionnaire survey was conducted by the Shanghai Nosocomial Infection Quality Control Center among full-time and part-time personnel of the nosocomial infection control administration across medical institutions at various levels and types in Shanghai using convenience sampling method. The questionnaire consisted of two parts: demographic information and professional competency assessment. The professional competency scale comprised four dimensions: fundamental cognition, basic skills, professional expertise, and personal qualities, totaling 35 items. ResultsA total of 1 179 questionnaires were distributed, with 1 144 valid responses collected, yielding an effective response rate of 97.03%. Statistically significant differences were observed among full-time and part-time personnel of the nosocomial infection control administration in terms of age (t=5.32, P=0.021), professional background (χ2=9.90, P=0.019), educational qualifications (χ2=19.10, P<0.001), professional titles (χ2=12.60, P=0.002), and the levels of medical institutions (χ2=111.08, P<0.001). The scores of full-time personnel of the nosocomial infection control administration in fundamental cognition [92 (82, 99) points] and basic skills [88 (78, 96) points] were significantly higher than those of part-time personnel(Z=-2.21, P=0.027;Z=-2.74, P=0.006). Statistically significant differences were found in fundamental cognition scores between full-time and part-time personnel of the nosocomial infection control administration regarding occupational safety protection, definition of healthcare-associated infection outbreaks, types of drug-resistant bacteria and their prevention and control strategies, and transmission routes of different infectious diseases (all P<0.05). Statistically significant differences were also observed in basic skills scores including proficient use of monitoring platforms, formulation and revision of standard operating procedures (SOPs), independent completion of targeted surveillance, guidance on basic infection control skills, guidance for key departments, and follow-up of personnel with occupational exposure (all P<0.05). However, no statistically significant differences were found in scores of professional knowledge and personal qualities (P>0.05). ConclusionThere are certain differences in professional competency between full-time and part-time personnel of the nosocomial infection control administration in Shanghai in terms of fundamental cognition and basic skills. Part-time personnel can effectively improve their professional competency through systematic training on basic infection control knowledge and practical skills, thereby comprehensively enhancing the overall quality of the nosocomial infection administration team.
8.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.
9.Effect of total flavones of Coreopsis tinctoria Nutt on vascular dementia by inhibiting miR-93-mediated TLR4 signaling pathway and its mechanism
Meng-ying HU ; Dong-mei YANG ; Yi-zhong ZHU ; Qin-lan LIANG ; Houwati NUERBAHETI ; Xiao-jun YANG ; Hasimu HAMULATI
Chinese Pharmacological Bulletin 2025;41(7):1237-1244
Aim To investigate the effect of total fla-vones of Coreopsis tinctoria Nutt(CF)on cognitive im-pairment in vascular dementia(VD).Methods The VD rat models were established by modified bilateral common carotid arteries ligation method.SD rats were divided into the sham operation group,model group,positive control group(nicergoline),and low,medium,and high dose CF groups.After eight weeks of admin-istration,the short term memory and spatial learning and memory abilities were evaluated by the platform jumping test,dark avoidance test and Morris water maze test.The pathological changes of the hippocam-pal tissues were inspected by HE and Nissl staining.The contents of TNF-α and IL-1β in the hippocampal were examined by ELISA.The protein expression lev-els of TLR4,MyD88,NF-κB p65,and p-NF-κB p65 in the hippocampal were detected by Western blot.The mRNA expression levels of miR-93,TLR4,MyD88,and NF-κB p65 in the hippocampal were determined by qRT-PCR.Results CF obviously improved the short term memory and spatial learning and memory abilities of VD rats,and alleviated the pathological damage of the hippocampus.CF also obviously decreased the lev-els of TNF-α and IL-1β,declined the protein expres-sion levels of TLR4,MyD88,and p-NF-κB p65,and re-duced the miR-93,TLR4,and MyD88 mRNA expres-sion in the hippocampus.Conclusion CF has a nota-ble protective effect on the neuroinflammation and cog-nitive impairments in VD rats by inhibiting the miR-93-mediated TLR4 signaling pathway.
10.Application of targeted degradomics in target identification of natural products
Yue-ying YANG ; Zhi-qi ZHANG ; Yang LIU ; Jing LIANG ; Hua LI ; Wen XU ; Li-xia CHEN
Chinese Pharmacological Bulletin 2025;41(6):1040-1046
Natural products are an important source for innovative drugs,but unclear molecular targets and mechanisms limit their further development and application.The authors proposed a new method for the target identification of natural products based on proteolysis-targeting chimera(PROTAC)technology and quantitative proteomics,and established the targeted degradomics(TGDO) technology for the identification of weak-affinity tar-gets.This article summarizes the standardized workflow and the application of TGDO for target identification of natural products.

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