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.Effect of Different Fermentation Conditions on Fungal Community and Chemical Composition of Aurantii Fructus
Zhihong YAN ; Xiumei LIU ; Qiuyan GUAN ; Yonggui SONG ; Zhifu AI ; Genhua ZHU ; Yuhui PING ; Ming YANG ; Qin ZHENG ; Huanhua XU ; Dan SU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):254-262
ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus, in order to obtain the optimal fermentation conditions and flora structure, and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2(ITS2) high-throughput sequencing, combined with fungal community diversity analysis and fungal community structure analysis, were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7, 14, 21 d(numbered Y1-Y3 for the former, and numbered F1-F3 for the latter), respectively. At the same time, the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS), combined with principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA) and compound retention time, parent ions, characteristic fragment ions and other information, the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method, while in the non-pressure-shelf natural fermentation method, there was a significant difference with the fermentation process, and at the genus level, the dominant genus of samples Y1, Y2, Y3 and F2 was Aspergillus, while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable, and the microbial community structure was more stable, which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis, including 70 flavonoids, 38 coumarins, 10 alkaloids, 34 organic acids and 3 other compounds. After fermentation, two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition, multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods, mainly including flavonoids, organic acids and coumarins. Comprehensively, the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable, the species richness was high and the overall content of differential compounds was high, which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation, the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds, and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus, as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.
3.Effect of Different Fermentation Conditions on Fungal Community and Chemical Composition of Aurantii Fructus
Zhihong YAN ; Xiumei LIU ; Qiuyan GUAN ; Yonggui SONG ; Zhifu AI ; Genhua ZHU ; Yuhui PING ; Ming YANG ; Qin ZHENG ; Huanhua XU ; Dan SU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):254-262
ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus, in order to obtain the optimal fermentation conditions and flora structure, and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2(ITS2) high-throughput sequencing, combined with fungal community diversity analysis and fungal community structure analysis, were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7, 14, 21 d(numbered Y1-Y3 for the former, and numbered F1-F3 for the latter), respectively. At the same time, the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS), combined with principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA) and compound retention time, parent ions, characteristic fragment ions and other information, the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method, while in the non-pressure-shelf natural fermentation method, there was a significant difference with the fermentation process, and at the genus level, the dominant genus of samples Y1, Y2, Y3 and F2 was Aspergillus, while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable, and the microbial community structure was more stable, which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis, including 70 flavonoids, 38 coumarins, 10 alkaloids, 34 organic acids and 3 other compounds. After fermentation, two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition, multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods, mainly including flavonoids, organic acids and coumarins. Comprehensively, the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable, the species richness was high and the overall content of differential compounds was high, which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation, the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds, and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus, as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.
4.International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025).
Sheng-Sheng ZHANG ; Lu-Qing ZHAO ; Xiao-Hua HOU ; Zhao-Xiang BIAN ; Jian-Hua ZHENG ; Hai-He TIAN ; Guan-Hu YANG ; Won-Sook HONG ; Yu-Ying HE ; Li LIU ; Hong SHEN ; Yan-Ping LI ; Sheng XIE ; Jin SHU ; Bin-Fang ZENG ; Jun-Xiang LI ; Zhen LIU ; Zheng-Hua XIAO ; Jing-Dong XIAO ; Pei-Yong ZHENG ; Shao-Gang HUANG ; Sheng-Liang CHEN ; Gui-Jun FEI
Journal of Integrative Medicine 2025;23(5):502-518
Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy*
;
Humans
;
Medicine, Chinese Traditional/methods*
;
Practice Guidelines as Topic
;
Drugs, Chinese Herbal/therapeutic use*
6.Association study of FADS2 gene rs174575 and rs2845574 single nucleotide polymorphisms with blood pressure and lipid levels in pregnant women
Yuwen GUO ; Huai BAI ; Linbo GUAN ; Xinghui LIU ; Ping FAN ; Yujie WU ; Suiyan LI
Chinese Journal of Medical Genetics 2025;42(6):675-683
Objective:To investigate the relationship between the single nucleotide polymorphisms (SNP) rs174575 and rs2845574 in the fatty acid desaturase 2 ( FADS2) gene and gestational diabetes mellitus (GDM). Methods:A total of 1 514 pregnant women who visited West China Second University Hospital, Sichuan University, between January 1, 2013, and December 31, 2021, were enrolled in this study. Among them, 583 were diagnosed with gestational diabetes mellitus (GDM group), and 931 had normal pregnancies (control group). The SNPs rs174575 and rs2845574 in the FADS2 gene were analyzed using Sanger DNA sequencing. Plasma levels, insulin (INS), apolipoprotein A1 (apoA1) and apolipoprotein B (apoB) levels were measured using enzymatic methods, chemiluminescence and immunoturbidimetry. This study was approved by Medical Ethics Committee of the West China Second University Hospital, Sichuan University (Ethics No. 2020-036). Results:① The main type of genotype at the rs174575 C/G and rs2845574 C/T polymorphic sites were CC in both GDM and control groups. No statistically significant differences were observed between the GDM and control groups regarding the genotype frequencies or allele frequencies of rs174575 and rs2845574 sites ( P>0.05). ② Among the GDM group, individuals with the GG genotype at the rs174575 site had lower plasma HDL-C levels compared to those with the CC genotype ( P<0.05), and had higher atherogenic indices (AI) than CC and CG genotype ( P<0.05; P<0.05). Individuals with the TT genotype at the rs2845574 site had higher AI than CT genotype ( P<0.05). Among the control group, individuals with the GG genotype had lower diastolic blood pressure (DBP) compared to those with the CC genotype ( P<0.05). ③ Additional subgroup analysis demonstrated that the rs174575 polymorphism was associated with AI levels in obesity subgroup of GDM, TG levels in non-obese subgroup of control and DBP levels in obese subgroup of control ( P<0.05; P<0.05; P<0.05). Conclusion:The FADS2 rs174575 and rs2845574 polymorphisms in GDM patients were associated wit HDL-C and AI levels, and the FADS2 rs174575 polymorphisms was also associated with DBP levels in normal pregnant women. The AI and DBP levels have BMI-dependent effect.
7.Association study of FADS2 gene rs174575 and rs2845574 single nucleotide polymorphisms with blood pressure and lipid levels in pregnant women.
Yuwen GUO ; Huai BAI ; Linbo GUAN ; Xinghui LIU ; Ping FAN ; Yujie WU ; Suiyan LI
Chinese Journal of Medical Genetics 2025;42(6):675-683
OBJECTIVE:
To assess the association between the single nucleotide polymorphisms (SNP) rs174575 and rs2845574 of the fatty acid desaturase 2 (FADS2) gene and gestational diabetes mellitus (GDM).
METHODS:
A total of 1 514 pregnant women who visited West China Second University Hospital of Sichuan University between January 1, 2013 and December 31, 2021 were enrolled in this study. Among them, 583 were diagnosed with gestational diabetes mellitus (GDM group), and 931 had normal pregnancies (control group). The SNPs rs174575 and rs2845574 of the FADS2 gene were analyzed using Sanger DNA sequencing. Plasma levels of insulin (INS), apolipoprotein A1 (apoA1) and apolipoprotein B (apoB) were measured using enzymatic methods, chemiluminescence and immunoturbidimetry. This study was approved by the Medical Ethics Committee of the West China Second University Hospital of Sichuan University (Ethics No.: 2020-036).
RESULTS:
The main genotype at the rs174575 C/G and rs2845574 C/T loci were CC in both GDM and control groups. No significant difference was found between the GDM and control groups regarding the genotypic or allelic frequencies of rs174575 and rs2845574 sites (P > 0.05). Among the GDM group, individuals with the GG genotype at the rs174575 site had lower plasma HDL-C levels compared to those with the CC genotype (P < 0.05), and had higher atherogenic indices (AI) compared with the CC and CG genotype (P < 0.05; P < 0.05). Individuals with the TT genotype at the rs2845574 site had higher AI compared with the CT genotype (P < 0.05). Among the control group, individuals with the GG genotype had lower diastolic blood pressure (DBP) compared to those with the CC genotype (P < 0.05). Additional subgroup analysis demonstrated that the rs174575 polymorphism was associated with AI levels in obesity subgroup of GDM, TG levels in non-obese subgroup of control and DBP levels in the obese subgroup of control (P < 0.05; P < 0.05; P < 0.05).
CONCLUSION
The FADS2 rs174575 and rs2845574 polymorphisms in GDM patients are associated wit HDL-C and AI levels, and the FADS2 rs174575 polymorphisms was also associated with DBP levels in normal pregnant women. The AI and DBP levels have a BMI-dependent effect.
Humans
;
Female
;
Pregnancy
;
Fatty Acid Desaturases/genetics*
;
Polymorphism, Single Nucleotide
;
Adult
;
Diabetes, Gestational/blood*
;
Blood Pressure/genetics*
;
Lipids/blood*
;
Genotype
;
Genetic Predisposition to Disease
8.Adherence to blood glucose self-monitoring guidance and glycemic control in Chinese patients with type 2 diabetes mellitus initiating basal insulin: A mobile health-based prospective cohort study.
Lixin GUO ; Dalong ZHU ; Kaining CHEN ; Yaoming XUE ; Chao ZHOU ; Ping LIU ; Zhaohui HU ; Pei GU ; Wei ZHANG ; Huijie DONG ; Wanjun XIE ; Liqing GUAN
Chinese Medical Journal 2025;138(21):2832-2834
9.Association among seminal oxidation-reduction potential,sperm DNA fragments and semen parameters in patients with varicocele
Xiao-chuan GUAN ; Yue-xin YU ; Ning ZHANG ; Jing ZHOU ; Jia-ping YU ; Yu WANG ; Xing-chi LIU ; Bo-lun WANG
National Journal of Andrology 2025;31(7):591-596
Objective:To investigate the relationship among seminal oxidation-reduction potential(nORP),sperm DNA frag-mentation(DFI)and semen parameters in patients with varicocele.Methods:Clinical data of 522 patients treated in the reproduc-tive andrology clinic of the Northern Theater General Hospital from November 2023 to December 2023 were retrospectively analyzed,in-cluding 435 men of childbearing age and 87 men of infertile age.The patients were divided into the varicocele group(n=116)and non-varicocele group(n=406)according to clinical diagnosis.The differences of seminal plasma nORP,DFI,sperm high DNA stain ability(HDS)and semen parameters were analyzed between the two groups.The relationship among general clinical data,seminal plasma nORP,semen parameters,DFI and HDS in patients with varicocele were further analyzed.According to the severity of varico-cele,the patients were divided into three groups,including mild,moderate and severe.And the differences of seminal plasma nORP and semen parameters,DFI and HDS among all groups were analyzed.The differences of seminal plasma nORP,semen parameters,DFI and HDS were compared between the varicocele and non-varicocele groups.Results:The total sperm count,sperm concentra-tion,progressive motility sperm percentage(PR%)and normal sperm morphology rate(NSMR)in patients with varicocele were sig-nificantly lower than those in control group(P<0.05).And seminal plasma nORP,DFI and HDS in patients with varicocele were sig-nificantly higher than those in control group(P<0.05).Seminal plasma nORP in patients with varicocele was significantly negatively correlated with total sperm,sperm concentration and NSMR(P<0.05),and significantly positively correlated with DFI and HDS(P<0.05).There were significant differences in nORP,total sperm count,sperm concentration,PR%,DFI and HDS among mild,moderate and severe varicocele groups(P<0.05).Seminal plasma nORP,sperm concentration,PR%and DFI in severe group were significantly lower than those in mild and moderate groups(P<0.05).Sperm count and HDS in severe group were significantly lower than those in mild group(P<0.05).In infertile patients,seminal plasma nORP,DFI and HDS in varicocele group were significantly higher than those in control group(P<0.05).And PR%in varicocele group was significantly lower than that in control group(P<0.05).Conclusions:Seminal plasma nORP in patients with varicocele may be an important marker of oxidative stress affecting DFI and semen parameters.
10.Association study of FADS2 gene rs174575 and rs2845574 single nucleotide polymorphisms with blood pressure and lipid levels in pregnant women
Yuwen GUO ; Huai BAI ; Linbo GUAN ; Xinghui LIU ; Ping FAN ; Yujie WU ; Suiyan LI
Chinese Journal of Medical Genetics 2025;42(6):675-683
Objective:To investigate the relationship between the single nucleotide polymorphisms (SNP) rs174575 and rs2845574 in the fatty acid desaturase 2 ( FADS2) gene and gestational diabetes mellitus (GDM). Methods:A total of 1 514 pregnant women who visited West China Second University Hospital, Sichuan University, between January 1, 2013, and December 31, 2021, were enrolled in this study. Among them, 583 were diagnosed with gestational diabetes mellitus (GDM group), and 931 had normal pregnancies (control group). The SNPs rs174575 and rs2845574 in the FADS2 gene were analyzed using Sanger DNA sequencing. Plasma levels, insulin (INS), apolipoprotein A1 (apoA1) and apolipoprotein B (apoB) levels were measured using enzymatic methods, chemiluminescence and immunoturbidimetry. This study was approved by Medical Ethics Committee of the West China Second University Hospital, Sichuan University (Ethics No. 2020-036). Results:① The main type of genotype at the rs174575 C/G and rs2845574 C/T polymorphic sites were CC in both GDM and control groups. No statistically significant differences were observed between the GDM and control groups regarding the genotype frequencies or allele frequencies of rs174575 and rs2845574 sites ( P>0.05). ② Among the GDM group, individuals with the GG genotype at the rs174575 site had lower plasma HDL-C levels compared to those with the CC genotype ( P<0.05), and had higher atherogenic indices (AI) than CC and CG genotype ( P<0.05; P<0.05). Individuals with the TT genotype at the rs2845574 site had higher AI than CT genotype ( P<0.05). Among the control group, individuals with the GG genotype had lower diastolic blood pressure (DBP) compared to those with the CC genotype ( P<0.05). ③ Additional subgroup analysis demonstrated that the rs174575 polymorphism was associated with AI levels in obesity subgroup of GDM, TG levels in non-obese subgroup of control and DBP levels in obese subgroup of control ( P<0.05; P<0.05; P<0.05). Conclusion:The FADS2 rs174575 and rs2845574 polymorphisms in GDM patients were associated wit HDL-C and AI levels, and the FADS2 rs174575 polymorphisms was also associated with DBP levels in normal pregnant women. The AI and DBP levels have BMI-dependent effect.

Result Analysis
Print
Save
E-mail