1.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.
2.Simultaneous Determination of Ten Kinds of Neonicotinoid Residues in Water for Aquaculture by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry
Li-Sha MA ; Yi YIN ; Lin-Ting WEI ; Qi SHAN ; Xiao-Xin DAI ; Shu-Gui LIU
Chinese Journal of Analytical Chemistry 2025;53(8):1352-1361,中插96-中插99
A solid-phase extraction-ultra-performance liquid chromatography-tandem mass spectrometry(SPE-UPLC-MS/MS)method was established for simultaneous determination of 10 kinds of neonicotinoid pesticide residues in aquaculture water.Based on the chemical properties of neonicotinoid pesticides and the matrix characteristics of aquaculture water,suitable temporary storage methods for water samples and appropriate solid-phase extraction columns were selected,and the extraction conditions(including elution solvents and sample loading volumes)were optimized.The method employed acetonitrile and 5 mmol/L ammonium acetate solution(containing 0.1%formic acid)as the mobile phase and an Oasis HLB solid-phase extraction column combined with PSA as a dispersive sorbent for sample purification.The method exhibited good linearity in detection of neonicotinoid in concentration range of 0.2-50 ng/mL(R2>0.99797),with a detection limit of 0.5 ng/L and a quantification limit of 1 ng/L,which were significantly lower than the maximum acceptable method detection limits(9-500 ng/L)for neonicotinoid insecticides in water published by the European Commission.In pond water,rice-fish water,and seawater,the average recoveries of the 10 target analytes were 74.6%-114.1%,with relative standard deviations ranging from 0.3%to 9.6%.Using this method,actual sample tests were conducted on the Pearl River water,Zhaoqing pond water,and Qingyuan rice-fish aquaculture water.The total concentration of five neonicotinoid pesticides in the Pearl River water ranged from 154.8 to 246.6 ng/L,the total concentration of four neonicotinoid pesticides in the Zhaoqing pond water was 95.0-176.1 ng/L,and the total concentration of three neonicotinoid pesticides in the Qingyuan rice-fish aquaculture water was 2.3-11.7 ng/L.This method was simple in operation,highly sensitive,and had strong resistance to interference.It was suitable for detection of trace neonicotinoid pesticides in aquaculture water and could provide technical support for construction of a green aquaculture environment and resolution of international trade disputes.
3.Preparation,Properties and In Vitro Release Behavior Study of Inclusion Complex of Taxifolin with 2-Hydroxypropyl-β-cyclodextrin
Shui-Xian MA ; Xin TAO ; Yun-Han YANG ; Sha XIA ; Yu-Xiang YANG ; Li YANG ; Li-Juan YANG
Chinese Journal of Analytical Chemistry 2025;53(10):1684-1693
The inclusion complex of taxifolin(TAX)with hydroxypropyl-β-cyclodextrin(HP-β-CD)was prepared by saturated aqueous solution method,and the preparation conditions such as molar ratio,volume ratio of solution,inclusion temperature and inclusion time were selected by single-factor experiment.The orthogonal design of three-level four-factor L9(34)was used to screen the preparation process of the inclusion complex,and the inclusion complex was prepared with optimal preparation process.The prepared inclusion complex was characterized by scanning electron microscopy(SEM),nuclear magnetic resonance(1H NMR,2D NMR),Fourier transform infrared spectroscopy(FT-IR),ultraviolet-visible(UV-Vis)absorption spectroscopy and X-ray powder diffraction(XRD).The inclusion ratio,biostability,solubility and in vitro release of the inclusion complex were investigated.The results of orthogonal experiments showed that the optimum conditions for preparation of the inclusion complex were as follows:the molar ratio of TAX to HP-β-CD was 1:1,the volume ratio of methanol to ultra-pure water was 1:8,the inclusion time was 8 h,and the inclusion temperature was 30℃.Under the optimal conditions,the inclusion ratio between TAX and HP-β-CD was calculated to be 1:1 by Job's curve method.According to the change of UV-vis absorption spectra,the host-guest complexation constant of 4.9488×104 L/mol was obtained by Benesi-Hildebrand curve method.The solubility of TAX increased from 1.2665 mg/mL to 19.3469 mg/mL after inclusion,demonstrating that HP-β-CD could serve as an effective host molecule for TAX,which could significantly enhance the bio-stability and solubility of the formed inclusion complex.
4.Diagnostic value of three-dimensional arterial spin labeling in patients with isolated vertigo due to posterior circulation ischemia
Qian LIU ; Rongchao MA ; Luna WANG ; Xuan HE ; Dujuan SHA
International Journal of Cerebrovascular Diseases 2025;33(2):93-100
Objective:To investigate the predictive value of three-dimensional arterial spin labeling (3D-ASL) for posterior circulation ischemia (PCI) and posterior circulation stroke (PCS) in patients with isolated vertigo.Methods:Patients with isolated vertigo underwent 3D-ASL imaging at Drum Tower Hospital Affiliated to Nanjing University School of Medicine from January 1, 2022 to December 31, 2024 were included retrospectively. According to the imaging findings, the patients with isolated vertigo were divided into PCI group and non-PCI group. The PCI group was further divided into PCS group and non-PCS group. The baseline clinical data and laboratory examination data were collected. Cerebral blood flow (CBF) in different brain regions of the posterior circulation was obtained through 3D-ASL related parameters to evaluate the posterior circulation perfusion, including CBF at two post-labeling delay times (PLD) (1.5 s and 2.5 s), delayed perfusion CBF (ΔCBF), multisequence PLD (Multi-PLD) CBF, and CBF under arterial transit time (ATT). Multivariate logistic regression analysis was used to determine the association of different CBF values with PCI and PCS in patients with isolated vertigo. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of different CBF values for PCI and PCS. Results:A total of 81 patients with isolated vertigo were included, aged 63.0±12.1 years, 44 were males (54.3%); 58 (71.6%) had PCI and 27 (25.9%) had PCS. Multivariate logistic regression analysis showed that PLD 1.5 s-CBF (odds ratio [ OR] 1.372, 95% confidence interval [ CI] 1.169-1.611; P<0.001), ΔCBF ( OR 1.197, 95% CI 1.072-1.336; P=0.001), and Multi-PLD-CBF ( OR 2.099, 95% CI 1.257-3.504; P=0.005) were the independent predictive factors of PCI. ROC curve analysis showed that the area under the curve for predicting PCI using the above three parameters alone and in combination were 0.962 (95% CI 0.915-1.000), 0.683 (95% CI 0.543-0.823), 0.944 (95% CI 0.985-1.000), and 0.999 (95% CI 0.997-1.000), respectively. Multivariate logistic regression analysis showed that the PLD 1.5 s-CBF ( OR 1.246, 95% CI 1.030-2.089; P=0.002), ΔCBF ( OR 1.153, 95% CI 1.038-1.281; P=0.008), and multi-PLD-CBF ( OR 1.388, 95% CI 1.219-1.689; P=0.001) in cerebellar region were the independent predictors of PCS. ROC curve analysis showed that the area under the curve for predicting PCS using the above three parameters alone and in combination were 0.956 (95% CI 0.911-1.00), 0.802 (95% CI 0.685-0.920), 0.972 (95% CI 0.923-1.000), and 0.977 (95% CI 0.937-1.00), respectively. Conclusion:3D-ASL can predict PCI and PCS early, and combining multiple parameters can improve the predictive ability for PCI and PCS.
5.Analysis of pancreatic cancer incidence and mortality in China from 1992 to 2021 based on the age-period-cohort model
Jiabao HU ; Sha HUA ; Wei CHEN ; Lina MA
Journal of International Oncology 2025;52(4):217-223
Objective:To analyze the incidence and mortality of pancreatic cancer in China from 1992 to 2021, and to explore the effects of age, period, and cohort on pancreatic cancer incidence and mortality.Methods:Data from the Global Burden of Disease Study (GBD) 2021 database were used to analyze the incidence and mortality of pancreatic cancer in China from 1992 to 2021. The Joinpoint software was applied to analyze the time trends of standardized incidence and mortality rates, and to calculate the average annual percentage change. An age-period-cohort model was constructed to analyze the effects of age, period, and birth cohort on the trends of pancreatic cancer incidence and mortality. The disease burden of pancreatic cancer deaths attributed to risk factors such as hyperglycemia and smoking was analyzed.Results:In 2021, the incidence of pancreatic cancer in China was 8.34/100 000, and the mortality rate was 8.41/100 000, representing increases of 150.45% and 145.19%, respectively, compared to 1992 (3.33/100 000 and 3.43/100 000) . By sex, the incidence (9.93/100 000) and mortality (9.91/100 000) rates in males in 2021 were higher than those in females (6.68/100 000 and 6.83/100 000) . From 1992 to 2021, the standardized incidence and mortality rates of pancreatic cancer in China showed upward trends, with average annual increases of 0.80% and 0.62%, respectively, both of which were statistically significant (both P<0.001) . Age effect results indicated a general increasing trend in pancreatic cancer incidence, with a steady rise in the 15-49 age group, a sharp increase after the age of 50, and a peak in the over 85 age group at 68.64/100 000. The mortality rate showed a slow increase in the 15-79 age group, with a marked rise and peak in the 80-84 age group at 196.51/100 000. Period effect results showed an overall upward trend in the period relative risk ( RR) for pancreatic cancer incidence, with the highest risk in 2017-2021 ( RR=1.09, 95% CI: 1.05-1.13, P=0.012) , compared to the reference period 2002-2006 ( RR=1) . The RR for pancreatic cancer mortality showed a fluctuating trend, with the highest risk in 2012-2016 ( RR=1.60, 95% CI: 1.07-2.38, P=0.021) , compared to the reference period 2002-2006 ( RR=1) . The results of cohort effect showed that the incidence and mortality risk of pancreatic cancer in China generally increased with the increase of years. With the 1952-1956 birth cohort as the reference cohort ( RR=1) , the incidence ( RR=1.18, 95% CI: 0.99-1.40, P=0.032) and mortality ( RR=1.63, 95% CI: 0.12-11.53, P=0.042) risk of pancreatic cancer were the highest in the 1987-1991 birth cohort, and showed decreasing trends after the 1992-1996 birth cohort. The proportion of pancreatic cancer deaths attributable to high blood glucose showed an increasing trend, while those attributable to smoking showed a decreasing trend. Conclusions:From 1992 to 2021, the standardized incidence and mortality rates of pancreatic cancer in China have continued to rise, with males having higher incidence and mortality rates than females. Age, period, and cohort all significantly influence the trends in pancreatic cancer incidence and mortality. The trend in pancreatic cancer deaths attributable to high blood glucose is increasing.
6.Analysis of the Characteristics of Rare Disease Outpatient Visits in a Children′s Hospital: A Single-Center Retrospective Study
Zhe LYU ; Kaichong JIANG ; Sha YIN ; Siyu FENG ; Ruiying MA ; Yanmin ZHANG
JOURNAL OF RARE DISEASES 2025;4(4):453-459
To analyze the characteristics of outpatient rare disease admissions at Xi′an Children′s Hospital based on the two batches of the China′s Rare Disease Catalogs. Based on the hospital information system, the outpatient visits of children with diseases included in the two batches of the rare disease catalogs from January 2018 to December 2023 at our center were retrieved and analyzed. A total of 93 602 outpatient visits of children with rare diseases were recorded, accounting for 0.71% of the total outpatient admissions during the same period. Among the diseases included in the two batches of the rare disease catalogs, 129 disease types were admitted, with a disease coverage rate of 62.32% (129/207). Specifically, 83 disease types (83/121, 68.60%) from the first batch of the catalog were admitted, with a total of 18 454 outpatient visits, showing an increasing trend year by year; 46 disease types (46/86, 53.49%) from the second batch of the catalog were admitted, with a total of 75 148 outpatient visits. The department of neurology admitted the most disease types, with a total of 54 types (54/207, 26.09%). Outpatient visits for single disease types exhibited multi-specialty characteristics, with 51.21% of the cases involving two or more specialties. Our center has admitted a relatively large number of children with rare diseases, covering most of the disease types that onset during childhood in the two batches of catalogs. There are obvious multi-specialty characteristics in outpatient admissions. The study results can provide data support for further optimizing the outpatient admission process for children with rare diseases and reasonably setting up multidisciplinary outpatient services.
7.Data Mining in Medication Rules of Chinese Herbal Concentrated-Granule for the Treatment of Hypertension
Yuxing SHUAI ; Sha ZHOU ; Liangjing WANG ; Jiasheng TIAN ; Zejun SHAN ; Tongjie CHEN ; Huilin MA ; Taichuan FENG ; Qing MA ; Jinrong CHANG ; Xinlin CHEN
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(7):1809-1816
Objective To analyze the medication rules of Chinese herbal concentrated-granule for the treatment of hypertension nationwide using data mining and knowledge graph methods,thus to provide evidence for expanding its application in treating hypertension.Methods From January 2022 to March 2023,Chinese herbal concentrated-granule prescriptions for hypertension prescribed by traditional Chinese medicine experts nationwide were collected.Microsoft Excel was used to analyze the frequency,properties and flavors,meridian tropism,and efficacy categories of the medicinals.Hierarchical clustering was applied for cluster analysis,and the Neo4j graph database was utilized to construct an information knowledge graph illustrating the relationships between regions and medicinals.Results A total of 2 600 Chinese herbal concentrated-granule prescriptions were included,involving 370 medicinals.The top six frequently-used medicinals were Poria(Fuling),Glycyrrhizae Radix et Rhizoma(Gancao),Atractylodis Macrocephalae Rhizoma(Baizhu),Citri Reticulatae Pericarpium(Chenpi),Paeoniae Radix Alba(Baishao),and Angelicae Sinensis Radix(Danggui).The properties of the medicinals were mainly warm and mild,and their flavors were usually sweet,pungent,and bitter.The medicinals frequently have the meridian tropism of the spleen,lung,and liver meridians.Hierarchical clustering yielded seven clusters.The information knowledge graph of region-medicinals relationships revealed that medicinals used in five or more regions were Baishao,Baizhu,Chenpi,Pinelliae Rhizoma(Banxia),Fuling,Gastrodiae Rhizoma(Tianma),Bupleuri Radix(Chaihu),Chuanxiong Rhizoma(Chuanxiong),Salviae Miltiorrhizae Radix et Rhizoma(Danshen),Danggui,Gancao,and Astragali Radix(Huangqi).Conclusion Chinese herbal concentrated-granule for hypertension usually consist of tonifying medicinals,with sweet and warm properties,and having the meridian tropism of the spleen meridian.And the medicinals composed of the prescriptions often have the actions of calming the liver and suppressing yang,strengthening the spleen and removing dampness,and nourishing the liver and kidney.
8.Prognostic Significance of KMT2D Gene Mutation and Its Co-mutated Genes in Patients with Diffuse Large B-Cell Lymphoma
Mutibaier·MIJITI ; Xiaolong QI ; Renaguli·ABULAITI ; Wenxin TIAN ; Sha LIU ; Weiyuan MA ; Zengsheng WANG ; Li AN ; Min MAO ; Muhebaier·ABUDUER ; Yan LI
Cancer Research on Prevention and Treatment 2025;52(2):127-132
Objective To explore the clinical characteristics of patients with diffuse large B-cell lymphoma (DLBCL) accompanied with KMT2D gene mutation and the impact of its co-mutated genes on prognosis. Methods Clinical data of 155 newly diagnosed DLBCL patients were obtained. The second-generation sequencing method was used to detect 475 hotspot genes, including KMT2D mutation. Patients were divided into the KMT2D mutation group and KMT2D wild-type group based on the presence or absence of KMT2D gene mutation. Clinical characteristics, differences in co-mutated genes, and survival differences between the two groups were compared. Results The frequency of KMT2D mutation was 31%, which is predominantly observed in elderly patients (P=0.07) and less in the double-expressor phenotype (P=0.07). Compared with the KMT2D wild-type group, KMT2D gene mutation was associated with higher co-mutation rates of CDKN2A (OR=2.82, P=0.01) and BCL2 (OR=3.84, P=0.016), while being mutually exclusive with MYC gene mutation (OR=0.11, P=0.013). In univariate survival analysis, no statistically significant difference in overall survival (OS) was found between the KMT2D mutation group and the wild-type group (P=0.54). Further analysis of the prognostic significance of KMT2D with other gene mutations indicated that patients with KMT2DmutBTG2mut had poorer OS than those with KMT2Dwt BTG2mut (P=0.07) and KMT2Dwt BTG2wt (P=0.05). On the contrary, patients with KMT2Dmut CD79Bmut had better OS than those with KMT2Dmut CD79Bwt (P=0.09), with no prognostic impact observed for other co-mutated genes. Multivariate Cox regression analysis revealed that Ann Arbor stages Ⅲ and Ⅳ (HR=2.751, 95%CI: 1.169-6.472, P=0.02), elevated LDH levels (HR=2.461, 95%CI: 1.396-4.337, P=0.002), Ki-67 index>80% (HR=1.875, 95%CI: 1.066-3.299, P=0.029), and KMT2DmutBTG2mut(HR=4.566, 95%CI: 1.348-15.471, P=0.015) were independent risk factors for OS in patients with DLBCL (P<0.05). Conclusion DLBCL patients with KMT2D mutation often have multiple gene mutations, among which patients with a co-mutated BTG2 gene have poor prognosis.
9.Clinical and Immunological Characteristics of Elderly Onset Rheumatoid Arthritis
Zhengfang LI ; Chanyuan WU ; Mengsi MA ; Tingting LI ; Xue WU ; Xinyan MENG ; Sha ZHANG ; Lijun WU
Medical Journal of Peking Union Medical College Hospital 2025;16(1):59-64
To investigate the clinical features and peripheral blood immune cell subsets ofelderly (≥60 years old) onset rheumatoid arthritis (EORA) patients. The patients with rheumatoid arthritis (RA) who were hospitalized in the Department of Rheumatology and Immunology of the People's Hospital of Xinjiang Uygur Autonomous Region from March 2023 to December 2023 were selected as the study objects. The demographic data, clinical characteristics, extra-articular manifestations and laboratory examination results of the patients were collected. The patients were divided into EORA group and young adult (< 60 years old)onset rheumatoid arthritis (YORA) group, and the clinical features and peripheral blood immunological indexes of the two groups were compared. A total of 187 RA patients with an average age of (62.1±12.0) years were enrolled, including 89 patients in the EORA group and 98 patients in the YORA group. Compared with YORA group, EORA group had a higher proportion of male patients(39.3% Compared with YORA, EORA has higher male proportion, joint disease degree and disease activity. EORA is prone to interstitial lung disease, anemia and high inflammation, and the level of peripheral blood NK cells is higher.
10.Phenylpropanoids from roots of Berberis polyantha.
Dong-Mei SHA ; Shuai-Cong NI ; Li-Niu SHA-MA ; Hai-Xiao-Lin-Mo MA ; Xiao-Yong HE ; Bin HE ; Shao-Shan ZHANG ; Ying LI ; Jing WEN ; Yuan LIU ; Xin-Jia YAN
China Journal of Chinese Materia Medica 2025;50(6):1564-1568
The chemical constituents were systematically separated from the roots of Berberis polyantha by various chromatographic methods, including silica gel column chromatography, HP20 column chromatography, polyamide column chromatography, reversed-phase C_(18) column chromatography, and preparative high-performance liquid chromatography. The structures of the compounds were identified by physicochemical properties and spectroscopic techniques(1D NMR, 2D NMR, UV, MS, and CD). Four phenylpropanoids were isolated from the methanol extract of the roots of B. polyantha, and they were identified as(2R)-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone-O-β-D-glucopyranoside(1), methyl 4-hydroxy-3,5-dimethoxybenzoate(2),(+)-syringaresinol(3), and syringaresinol-4-O-β-D-glucopyranoside(4). Compound 1 was a new compound, and other compounds were isolated from this plant for the first time. The anti-inflammatory activity of these compounds was evaluated based on the release of nitric oxide(NO) in the culture of lipopolysaccharide(LPS)-induced RAW264.7 macrophages. At a concentration of 10 μmol·L~(-1), all the four compounds inhibited the LPS-induced release of NO in RAW264.7 cells, demonstrating potential anti-inflammatory properties.
Plant Roots/chemistry*
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Animals
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Mice
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Berberis/chemistry*
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RAW 264.7 Cells
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Macrophages/immunology*
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Drugs, Chinese Herbal/isolation & purification*
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Nitric Oxide/metabolism*
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Molecular Structure
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Anti-Inflammatory Agents/isolation & purification*

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