1.Arginine Metabolic Disorder in Heart Failure Rats: Analysis Based on Targeted Metabolomics and Bioinformatics
Zeyu LI ; Xiaoqing WANG ; Zhengyu FANG ; Yurou ZHAO ; He XIAO ; Penghaobang LIU ; Haiming ZHANG ; Chunyan LIU ; Yanhong HU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):229-237
ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure (HF), providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine (TCM). MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats, which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group, with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-S), and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging (AFADESI-MSI). Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus (GEO), a protein-protein interaction (PPI) network was constructed, and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) was performed. Finally, molecular docking was conducted to verify the binding between core metabolic components and key targets, and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group, the levels of arginine and citrulline in the serum of model rats were significantly decreased (P<0.01), while those of proline, ornithine, creatine, creatinine and glutamate were significantly increased (P<0.05, P<0.01). Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets, such as the angiotensin-converting enzyme (ACE), neuronal nitric oxide synthase (NOS1), 5-hydroxytryptamine receptor 2A (HTR2A), and epidermal growth factor receptor (EGFR), and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway, neuroactive ligand-receptor interactions, and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine, citrulline and HTR2A, as well as between creatine, creatinine and EGFR. Based on pathway-target prediction, potential TCM interventions, such as ginseng and magnolia, were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF, and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways, and offers valuable insights for targeted therapy of HF and the development of TCM.
2.Arginine Metabolic Disorder in Heart Failure Rats: Analysis Based on Targeted Metabolomics and Bioinformatics
Zeyu LI ; Xiaoqing WANG ; Zhengyu FANG ; Yurou ZHAO ; He XIAO ; Penghaobang LIU ; Haiming ZHANG ; Chunyan LIU ; Yanhong HU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):229-237
ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure (HF), providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine (TCM). MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats, which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group, with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-S), and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging (AFADESI-MSI). Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus (GEO), a protein-protein interaction (PPI) network was constructed, and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) was performed. Finally, molecular docking was conducted to verify the binding between core metabolic components and key targets, and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group, the levels of arginine and citrulline in the serum of model rats were significantly decreased (P<0.01), while those of proline, ornithine, creatine, creatinine and glutamate were significantly increased (P<0.05, P<0.01). Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets, such as the angiotensin-converting enzyme (ACE), neuronal nitric oxide synthase (NOS1), 5-hydroxytryptamine receptor 2A (HTR2A), and epidermal growth factor receptor (EGFR), and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway, neuroactive ligand-receptor interactions, and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine, citrulline and HTR2A, as well as between creatine, creatinine and EGFR. Based on pathway-target prediction, potential TCM interventions, such as ginseng and magnolia, were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF, and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways, and offers valuable insights for targeted therapy of HF and the development of TCM.
3.Thyroid Hormone Network Regulation in MASLD: Mechanisms and Targeted Therapies
Wen-Ping XIAO ; Yang MA ; Heng GUAN ; Sha WAN ; Wen HAN ; Bing-Bing LUO ; Wu-Feng WANG ; Fang LIU
Progress in Biochemistry and Biophysics 2026;53(3):643-661
Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disease worldwide, affecting approximately 32%-38% of the adult population and posing a growing public health burden. MASLD represents a continuous disease spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), progressive hepatic fibrosis, cirrhosis, and ultimately hepatocellular carcinoma (HCC). The pathological core of MASLD lies in disruption of hepatic lipid metabolic homeostasis, characterized by an imbalance among de novo lipogenesis, fatty acid β-oxidation, and very-low-density lipoprotein (VLDL)-mediated lipid export. This metabolic disequilibrium subsequently drives inflammatory injury and fibrotic progression. Among the multiple regulatory pathways involved, thyroid hormone (TH) signaling has emerged as a central regulator of hepatic metabolic homeostasis. The liver is a major peripheral target organ of TH action, where TH predominantly exerts its metabolic effects through thyroid hormone receptor β (TRβ). Large-scale epidemiological studies and meta-analyses have demonstrated that hypothyroidism is significantly associated with increased MASLD prevalence, more severe histological injury, and advanced hepatic fibrosis, suggesting that dysregulation of TH signaling may participate throughout the entire MASLD disease spectrum. At the molecular level, TH regulates hepatic lipid metabolism by coordinating suppression of lipogenesis, enhancement of mitochondrial fatty acid oxidation, and promotion of VLDL assembly and secretion through integrated genomic actions of the T3-TRβ axis and non-genomic signaling pathways. Across different stages of MASLD, TH signaling exerts stage-dependent protective effects. In the steatosis stage, TH improves metabolic flexibility by modulating insulin sensitivity, glucose metabolism, and lipid droplet clearance, thereby alleviating early lipotoxic stress. During progression to MASH, TH attenuates inflammatory amplification by improving mitochondrial homeostasis, suppressing activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, and modulating the gut-liver axis microenvironment. In advanced stages, TH signaling influences hepatic stellate cell activation and extracellular matrix deposition, partly through interaction with the transforming growth factor-β (TGF-β)/SMAD pathway, while alterations in intrahepatic TH availability, mediated by dynamic changes in iodothyronine deiodinase 1 (DIO1), contribute to fibrosis progression and hepatocellular dedifferentiation. In hepatocellular carcinoma, coordinated downregulation of TRβ and DIO1 establishes a tumor-associated hypothyroid state that promotes metabolic reprogramming and tumor progression. The clinical relevance of TH signaling in MASLD has been underscored by the recent approval of Resmetirom, a liver-targeted TRβ‑selective agonist, for the treatment of non-cirrhotic MASH with moderate-to-severe fibrosis (F2-F3). This approval represents a landmark transition from mechanistic understanding to metabolism-centered precision therapy in MASLD. Clinical trials have demonstrated that Resmetirom not only improves key histological endpoints, including MASH resolution and fibrosis regression, but also favorably modulates atherogenic lipid profiles, highlighting the therapeutic potential of selectively targeting hepatic TH pathways. This review systematically summarizes the multidimensional regulatory roles of TH across the MASLD disease spectrum and discusses emerging diagnostic and therapeutic implications of TH-based interventions, aiming to inform future mechanistic research and optimize clinical management strategies.
4.Impact of birth weight on the trajectory of blood pressure among primary school students
CUI Chengpeng, YE Siyan, FANG Yanfei, LI Yan, PENG Zeqin, XIAO Yuqing, WU Meng, LIU Qin
Chinese Journal of School Health 2026;47(3):309-313
Objective:
To explore the early effects of birth weight at different gestational ages on blood pressure trajectory among primary school students, so as to provide evidence for incorporating gestational age birth weight into individualized early warning and intervention strategies for childhood hypertension.
Methods:
From May to November 2023, a purposeful sampling method was used to recruit 1 676 students in grade 1-3 from three primary schools in a certain urban district of Chongqing. Follow up assessments were conducted in May 2024(T1), November 2024(T2), and May 2025(T3). General demographic and birth related information were collected via self administered questionnaires, while height, weight and blood pressure were obtained through physical examinations. Linear mixed effects model was used to analyze the associations between birth weight at different gestational ages and blood pressure trajectories.
Results:
During the T1-T3 period, the systolic blood pressure of boys were 98.5 (93.0, 104.5 ),98.5 (93.5, 105.0), and 97.5 (92.5, 103.5)mmHg, respectively, while the diastolic blood pressure were 60.5 (56.5, 65.0), 61.5 ( 57.0 , 65.5), and 60.0 (56.0, 64.0)mmHg, respectively. For girls, the systolic blood pressure were 95.5 (90.0, 102.0),95.5 (90.5, 101.5), and 96.0 (90.5, 101.5)mmHg, respectively, and the diastolic blood pressure were 60.5 (56.0, 64.5 ),61.5 (57.5, 65.5), and 59.5 (56.0, 63.0)mmHg, respectively. Through Friedman test within both boys and girls, diostolic blood pressure were statistically significant across three measurements( χ 2=48.85,81.54,both P <0.01). The proportion of normal blood pressure increased , and the proportion of prehypertension and hypertension decreased with time( χ 2=39.72,25.62,both P < 0.01 ). Linear mixed effects model analysis revealed that after adjusting for age, sex, household income monthly, parental education, family history of hypertension and maternal pregnancy complications, large for gestational age had significantly higher trajectories of systolic ( β = 1.50) and diastolic( β =0.94) blood pressure compared to appropriate for gestational age(both P <0.01).
Conclusion
Large for gestational age is associated with elevated blood pressure trajectories during school age, and it may be considered as an early indicator for individualized screening and intervention for childhood hypertension.
5.Experience of Professor LIU Shangyi in Treating Acute Mastitis from the Perspective of "Membrane Collaterals"
Fang ZHANG ; Dongyang DENG ; Xiao LIU ; Rong WEI ; Ling WANG ;
Journal of Traditional Chinese Medicine 2026;67(11):1148-1152
This paper summarizes Professor LIU Shangyi's clinical experience in treating acute mastitis based on the "membrane collaterals" theory. It is considered that constraint and stagnation of the membrane collaterrals is the primary pathogenic factor, with damp, heat, phlegm, and stasis being the secondary manifestations. If untreated, the condition can progress to heat toxin injuring the membrane. In treatment, the emphasis is diffusing and unblocking membrane collaterals, unblocking breast and relieving constraint. The clinical course of the disease can be divided into three stages including the early stage with mild constraint heat, the middle stage with escalating toxic heat, and the later stage with a decline of pathogens but deficiency of healthy qi. In correspondence, self-made Tongru Formula (通乳方) for diffusing membrane and venting constraint, self-made Toumo Jiedu Formula (透膜解毒方) for unblocking membrane and relieving toxin, and Tuoli Xiaodu Powder (托里消毒散) with modifications for restoring membrane and rectifying healthy qi should be used, respectively.
6.Construction and validation of a predictive model for visual outcome after vitrectomy for polypoidal choroidal vasculopathy combined with vitreous hemorrhage
Qing XIAO ; Chenwei LIU ; Lingna LI ; Guangbao TANG ; Mingxia DONG ; Dongyu LI ; Fang LIU
International Eye Science 2025;25(2):274-280
AIM:To analyze the influencing factors of visual outcome after vitrectomy for polypoidal choroidal vasculopathy(PCV)combined with vitreous hemorrhage and establish a predictive model.METHODS: A retrospective analysis was conducted on the clinical data of 129 cases(129 eyes)of patients who underwent vitrectomy for PCV combined with vitreous hemorrhage from June 2021 to January 2024 in our hospital. They were divided into elevated group(71 eyes)and non-elevated group(58 eyes)according to visual outcome at early posoperative stage(within 24 mo). Another 30 cases(30 eyes)of PCV with vitreous hemorrhage undergoing vitrectomy were selected as external validation data. The predictive value of the model for the postoperative visual outcomes of both internal and external populations was evaluated.RESULTS: The non-elevated group had a higher proportion of patients aged ≥60 years, diabetes, continuous abnormalities of the ellipsoid zone(EZ)during surgery, bleeding involving the macular fovea, and postoperative retinal scar formation than the elevated group were independent factors affecting postoperative visual acuity(all P<0.05). The AUC of the predictive model for predicting the postoperative visual outcomes of internal and external populations was 0.824(95%CI: 0.750-0.898)and 0.809(95%CI: 0.723-0.865), respectively.CONCLUSION:Patients aged ≥60 years, diabetes, intraoperative continuous abnormalities of EZ, bleeding involving the macular fovea, and postoperative retinal scar formation are influencing factors for visual outcome after vitrectomy in patients with PCV combined with vitreous hemorrhage. A predictive model based on those factors has been established, which has a certain predictive value for postoperative visual outcome.
7.A case of recurrent atypical lipomatous tumor originating from cervical lipoma
Yi GAO ; Tingting LIU ; Weixiang NI ; Junwei FANG ; Weixuan HONG ; Lie WANG ; Chunhong XIAO
Journal of Clinical Surgery 2025;33(8):895-896
Adipocytic tumors are the most common type of soft tissue tumors,which can be divided into lipomas and liposarcomas.Studies have found that benign lipomas resected from the same site can transform into liposarcomas,especially atypical lipomatous tumors(ALT),suggesting an underlying biological association.In this case,the patient underwent resection of a right neck mass in our hospital in 2017,and the pathology showed fibrolipoma.One year later,the mass recurred at the original site but was not treated.By 2023,the mass had significantly enlarged and extended deeply.MRI showed that the lesion had an unclear boundary with the surrounding fat,suggesting liposarcoma.Puncture and molecular pathology showed MDM2 gene amplification,and the diagnosis of ALT was made,which was confirmed by pathology after complete surgical resection.It can be seen that adipocytic tumors have great differences in biological behavior,and benign lipomas can transform into liposarcomas(especially ALT).Clinically,it is necessary to combine imaging,pathology and molecular detection(such as MDM2/CDK4)for differentiation to formulate treatment plans.
8.Quality Evaluation of Cisatracurium Besilate Injection
Jing FANG ; Xinying YU ; Kai DUO ; Biwei BAI ; Yu HAN ; Kexin XIAO ; Xinying MA ; Liqun LIU ; Jialiang ZHU
Herald of Medicine 2025;44(1):31-38
Objective To evaluate the quality of cisatracurium besilate injection produced by domestic manufacturers.Methods A comprehensive evaluation of 104 batches of samples was carried out using statutory testing methods combined withexploratory research,including related substances,1,5-pentanediol diacrylate,residual solvents,genotoxic impurities of benzenesulfonate esters,infrared spectrum,and endotoxin examination.The quality of domestic products and the controllability of current specifications were comprehensively evaluated.Results According to the statutory tests,the qualified rate of 104 batches of samples was 100.0%.The exploratory research showed that the results of related substances in the samples produced by 6 manufacturers were far below the limit,and no genotoxic impurities of benzenesulfonate esters were detected.However,the results showed that there was variability in 1,5-pentanediol diacrylate,as well as residual solvents.Conclusions The quality of the cisatracurium besilate injection is good,and the current specifications should be further improved and unified.It was proposed that the infrared spectrum,related substance,and 1,5-pentanediol diacrylate method be added or revised,and the limit of endotoxin strictly controlled.It was proposed that manufacturers pay attention to the quality of API and control injection production.
9.Atomic force microscopic observation of surface structure of purified protein molecules in vitro
Zhao-ying CHEN ; Xiao-feng FANG ; Dan-yan LIU ; Meng-qin CHEN ; Xi LING ; Jie-min ZHAO ; Wei WEI ; Yu-jing WU
Chinese Pharmacological Bulletin 2025;41(1):193-199
Aim To compare the observation results of atomic force microscopy(AFM)and scanning electron microscopy(SEM),and to summarize the main problems and solutions of AFM in observing biological macromolecules,using the observa-tion subjects of protein samples purified by our research group.Methods The protein samples were diluted to 15 nmol·L-1 with PBS,fixed on glass slides,silicon wafers,and mica sheets,dried,and made into solid-phase observation samples.SEM sam-ples were plated with platinum before observation.The surface structures of proteins were observed using AFM and SEM,sample heights were calculated,and differences in results were com-pared.Results Protein samples with positive charges tended to shift to the right during observation due to the repulsion of the AFM probe;mica sheets could effectively eliminate the positive charge of proteins to avoid sample movement;PBS provided a stable environment for protein samples,but the crystallization of PBS salts interfered with probe operation and imaging clarity;SEM samples needed to be plated with platinum before observa-tion and could not achieve the precision of AFM.Conclusions Both AFM and SEM can directly observe protein structures in vitro,with AFM providing higher precision results;when protein sample stability permits,ultrapure water is preferred as the sol-vent carrier,and volatile liquids such as ethanol can also serve as solvent carriers.The application of AFM offers a new approach for pharmacological studies on interactions between biological macromolecules.
10.PM2.5 exposures exacerbate bleomycin-induced idiopathic pulmonary fibrosis in mice by regulating ferroptosis via Nrf2/SLC7A11/GPX4 axis
Jin-beng DING ; De-qi KONG ; Hui-min HUANG ; Yu GU ; Yue-bing CHEN ; Rui-li ZHAO ; Su-xiao LIU ; Xue-fang LIU ; Ya LI
Chinese Pharmacological Bulletin 2025;41(2):333-339
Aim To explore the mechanisms of PM2.5 exposure exacerbating bleomycin(BLM)-induced idio-pathic pulmonary fibrosis(IFP)by regulating ferropto-sis via nuclear factor 2 related factor 2(Nrf2)/solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase(GPX)4 axis.Methods Forty C57BL/6J mice were randomized into the control,BLM,PM2.5,BLM+PM2.5 and sulforaphane(SFN,Nrf2 agonist)groups,with eight mice in each group.PM2.5 expo-sures were conducted to the BLM-induced IPF mice for two weeks.The lung function was measured,and the content of hydroxyproline(HYP)in lung tissue and the pathomorphology of lungs were observed.Reactive oxygen species(ROS),malondialdehyde(MDA),ferrous ion(Fe2+)and glutathione(GSH)of the lung tissue were measured by ELISA.The mRNA and pro-teins levels of Nrf2,SLC7A11,GPX4,collagen typeⅠ(COL-1),α-smooth muscle actin(α-SMA)were measured by quantitative polymerase chain reaction(qPCR)and Western blot.Results Compared with the control group,the lung function of mice was signif-icantly reduced(P<0.01)in the BLM and PM2.5 groups,while lung tissue showed the characteristic pathological changes of pulmonary fibrosis such as a large number of inflammatory cell infiltration,alveolar wall fracture,thickening,collagen deposition,and sig-nificantly increased HYP,Fe2+,ROS,MDA(P<0.05,P<0.01),genes and proteins of COL-1,α-SMA(P<0.01);and decreased GSH,Nrf2,SLC7A11,GPX4 genes and proteins(P<0.05,P<0.01).The above-mentioned lesions were markedly aggravated in the BLM+PM2.5 group compared with the BLM(P<0.05)and PM2.5 groups(P<0.01),and were also improved in the SFN group(P<0.05,P<0.01).Conclusions PM2.5 exposures can exac-erbate IPF-induced IPF in mice,and the regulating of Nrf2/SLC7 A1 1/GPX4 axis and ferroptosis might be in-volved in the related mechanisms.


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