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.The Effect of Serum Ferritin before Transplantation on Implanta-tion in MDS and AML Patients after Unrelated Cord Blood Trans-plantation
Dan-Dan HAN ; Hui-Ru WANG ; Xiao-Ju WAN ; Juan LI ; Hui-Lan LIU
Journal of Experimental Hematology 2025;33(6):1797-1802
Objective:To analyze the effect of high serum ferritin(SF)before transplantation on erythrocyte,granulocyte and platelet implantation in unrelated cord blood transplantation(UCBT)patients with myelodysplastic syndrome(MDS)and acute myeloid leukemia(AML).Methods:The medical records of 60 patients with MDS and AML who underwent UCBT in the First Affiliated Hospital of University of Science and Technology of China from January 2020 to December 2022 were retrospectively collected.According to the SF level before transplantation,they were divided into high SF group(SF ≥ 1 000 μg/L,n=20)and non-high SF group(SF<1 000 μg/L,n=40).The red blood cell(RBC)infusion volume before transplantation,implantation time of RBC,granulocyte and platelet,implantation risk and prognosis were analyzed and compared between the two groups.Results:There was no correlation between the level of SF before transplantation and RBC infusion.After transplantation,the median implantation time of RBC in the high SF group was 28.5(14-149)d,which was longer than 21(10-83)d in the non-high SF group(P<0.05).The median time of granulocyte engraftment in the high SF group was 16.5(12-63)d,while that in the non-high SF group was 16(12-49)d,with no statistical difference between the two groups(P>0.05).The median platelet engraftment time in the high SF group was 45(12-206)d,while that in the non-high SF group was 35.5(14-149)d,with no statistical difference between the two groups(P>0.05).Kaplan-Meier cumulative implantation probability analysis showed that the rate of erythroid implantation in the non-high SF group was higher than that in the high SF group(P<0.05),while there was no significant difference in the rates of granulocyte and platelet implantation between the two groups(P>0.05).The 1-year overall survival rates of the non-high SF group and high SF group were 95%and 90%,respectively,with no statistical difference between the two groups(P>0.05).Conclusion:SF levels before cord blood transplantation in MDS and AML patients have an impact on post transplant erythroid implantation.Detecting and intervening of iron load in patients before transplant may be beneficial for improving implantation and prognosis.
3.Preferences for achievements transformation of Traditional Chinese Medicine(TCM)Preparation among medical staff in TCM hospitals in Beijing
Yi-xuan CHEN ; Xue-feng SHI ; Wan-jin YANG ; Xin-qi GENG ; Han-lin NIE ; Ming-li MA ; Xiao-wei NIU ; Yao-qi WANG
Chinese Journal of Health Policy 2025;18(11):66-73
Objective:To analyze the preferences of medical staff in TCM hospitals in Beijing regarding the achievements transformation of hospital traditional Chinese medicine preparations,and to provide a reference for formulating incentive policies.Methods:233 medical staff from five TCM hospitals in Beijing were taken as the research objects,and surveyed with a questionnaire designed based on the discrete choice experiment(DCE).Mixed logit models and latent class models were then used to analyze their transformation preferences.Results:The mixed Logit model revealed that seven key attributes significantly influenced medical staff's preferences for the achievements transformation of traditional Chinese medicine preparations(P<0.05).Latent class analysis identified three distinct preference groups among respondents:an organization-dependent group(27.0%),a pro-transformation group(61.4%),and a conservative group(11.6%).Conclusions:Medical Staff preferred transformation conditions that increased monthly income;utilized"human use+re-experimentation";involved the hospital's achievements transformation department as the entity;were funded by the hospital;offered a 70%profit share;enabled promotion three years earlier,and assigned patents to the hospital.The study recommends implementing diverse incentive measures and developing differentiated strategies tailored to the distinct Medical Staff categories to facilitate the transformation of hospital traditional Chinese medicine preparations into new drugs.
4.Cell components of tumor microenvironment in lung adenocarcinoma: Promising targets for small-molecule compounds.
Mingyu HAN ; Feng WAN ; Bin XIAO ; Junrong DU ; Cheng PENG ; Fu PENG
Chinese Medical Journal 2025;138(8):905-915
Lung cancer is one of the most lethal tumors in the world with a 5-year overall survival rate of less than 20%, mainly including lung adenocarcinoma (LUAD). Tumor microenvironment (TME) has become a new research focus in the treatment of lung cancer. The TME is heterogeneous in composition and consists of cellular components, growth factors, proteases, and extracellular matrix. The various cellular components exert a different role in apoptosis, metastasis, or proliferation of lung cancer cells through different pathways, thus contributing to the treatment of adenocarcinoma and potentially facilitating novel therapeutic methods. This review summarizes the research progress on different cellular components with cell-cell interactions in the TME of LUAD, along with their corresponding drug candidates, suggesting that targeting cellular components in the TME of LUAD holds great promise for future theraputic development.
Humans
;
Tumor Microenvironment/drug effects*
;
Adenocarcinoma of Lung/drug therapy*
;
Lung Neoplasms/pathology*
;
Adenocarcinoma/metabolism*
;
Animals
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Apoptosis/physiology*
5.The Effect of Serum Ferritin before Transplantation on Implanta-tion in MDS and AML Patients after Unrelated Cord Blood Trans-plantation
Dan-Dan HAN ; Hui-Ru WANG ; Xiao-Ju WAN ; Juan LI ; Hui-Lan LIU
Journal of Experimental Hematology 2025;33(6):1797-1802
Objective:To analyze the effect of high serum ferritin(SF)before transplantation on erythrocyte,granulocyte and platelet implantation in unrelated cord blood transplantation(UCBT)patients with myelodysplastic syndrome(MDS)and acute myeloid leukemia(AML).Methods:The medical records of 60 patients with MDS and AML who underwent UCBT in the First Affiliated Hospital of University of Science and Technology of China from January 2020 to December 2022 were retrospectively collected.According to the SF level before transplantation,they were divided into high SF group(SF ≥ 1 000 μg/L,n=20)and non-high SF group(SF<1 000 μg/L,n=40).The red blood cell(RBC)infusion volume before transplantation,implantation time of RBC,granulocyte and platelet,implantation risk and prognosis were analyzed and compared between the two groups.Results:There was no correlation between the level of SF before transplantation and RBC infusion.After transplantation,the median implantation time of RBC in the high SF group was 28.5(14-149)d,which was longer than 21(10-83)d in the non-high SF group(P<0.05).The median time of granulocyte engraftment in the high SF group was 16.5(12-63)d,while that in the non-high SF group was 16(12-49)d,with no statistical difference between the two groups(P>0.05).The median platelet engraftment time in the high SF group was 45(12-206)d,while that in the non-high SF group was 35.5(14-149)d,with no statistical difference between the two groups(P>0.05).Kaplan-Meier cumulative implantation probability analysis showed that the rate of erythroid implantation in the non-high SF group was higher than that in the high SF group(P<0.05),while there was no significant difference in the rates of granulocyte and platelet implantation between the two groups(P>0.05).The 1-year overall survival rates of the non-high SF group and high SF group were 95%and 90%,respectively,with no statistical difference between the two groups(P>0.05).Conclusion:SF levels before cord blood transplantation in MDS and AML patients have an impact on post transplant erythroid implantation.Detecting and intervening of iron load in patients before transplant may be beneficial for improving implantation and prognosis.
6.Preferences for achievements transformation of Traditional Chinese Medicine(TCM)Preparation among medical staff in TCM hospitals in Beijing
Yi-xuan CHEN ; Xue-feng SHI ; Wan-jin YANG ; Xin-qi GENG ; Han-lin NIE ; Ming-li MA ; Xiao-wei NIU ; Yao-qi WANG
Chinese Journal of Health Policy 2025;18(11):66-73
Objective:To analyze the preferences of medical staff in TCM hospitals in Beijing regarding the achievements transformation of hospital traditional Chinese medicine preparations,and to provide a reference for formulating incentive policies.Methods:233 medical staff from five TCM hospitals in Beijing were taken as the research objects,and surveyed with a questionnaire designed based on the discrete choice experiment(DCE).Mixed logit models and latent class models were then used to analyze their transformation preferences.Results:The mixed Logit model revealed that seven key attributes significantly influenced medical staff's preferences for the achievements transformation of traditional Chinese medicine preparations(P<0.05).Latent class analysis identified three distinct preference groups among respondents:an organization-dependent group(27.0%),a pro-transformation group(61.4%),and a conservative group(11.6%).Conclusions:Medical Staff preferred transformation conditions that increased monthly income;utilized"human use+re-experimentation";involved the hospital's achievements transformation department as the entity;were funded by the hospital;offered a 70%profit share;enabled promotion three years earlier,and assigned patents to the hospital.The study recommends implementing diverse incentive measures and developing differentiated strategies tailored to the distinct Medical Staff categories to facilitate the transformation of hospital traditional Chinese medicine preparations into new drugs.
7.Clinical significance of detecting group B Streptococcus from midstream urine culture
Xing-Long CAI ; Xiao-Li CAO ; Jing-Jing LIU ; Shuo GAO ; Han SHEN ; Wan-Qing ZHOU
Chinese Journal of Infection Control 2024;23(3):277-283
Objective To explore the clinical significance and antimicrobial resistance of group B Streptococcus(GBS)isolated from midstream urine culture,aiming to provide a basis for the diagnosis and treatment of clinical urinary tract infection(UTI).Methods Information about GBS strains isolated from midstream urine culture of in-patients and outpatient in a hospital in Nanjing from February 2020 to December 2022 were retrieved through labora-tory information system,strains with complete data were screened out.Case data,urine routine,and antimicrobial susceptibility testing results were reviewed.Results A total of 9 081 non-repetitive bacterial strains were detected from midstream urine culture,including 425 GBS strains,accounting for 4.7%,ranking sixth.Strains with incom-plete data were excluded,a total of 365 patients were included in the study.169(46.3%)were males and 196(53.7%)were females,with an average age of(55.4±15.2)years.365 patients who were detected GBS were from 17 de-partments,with the highest proportion being department of urology(n=237,64.9%).The underlying diseases of patients mainly included hypertension(n=136),diabetes(n=95),urolithiasis(n=120)and urinary tumors(n=98).211 patients underwent urological surgery,all were treated with antimicrobial agents before surgery,and 205 patients underwent indwelling urinary catheters after surgery;9 patients were detected GBS from urine during the middle and advanced stage of pregnancy.36.4%(n=133),38.9%(n=142)and 24.7%(n=90)patients had GBS colony count ≤104 CFU/mL,104-105 CFU/mL,and ≥105 CFU/mL,respectively.Patients with symptoms of UTI accounted for 24.9%(n=91),and asymptomatic bacteriuria accounted for 75.1%(n=274).The incidence of UTI symptoms in males was lower than that in females(19.5%vs 29.6%,P<0.05).As the GBS colony count in urine culture increased,the proportion of patients with symptoms of UTI showed an upward trend(P<0.05).On the day of urine culture,the positive rates of urine routine white blood cells,leukocyte esterase,and nitrite were 53.2%,50.1%,and 3.8%,respectively.The positive rates of urine occult blood,leukocyte esterase,white blood cells,and urine protein in patients with symptomatic UTI were all higher than those with asymptomatic bacteriuria patients(all P<0.05).No GBS were found to be resistant to penicillin,ampicillin,vancomycin,linezolid,and tigecycline.The resistance rate to levofloxacin and moxifloxacin was about 40%,and resistance rate to tetracycline and clindamycin was over 60%.Conclusion GBS isolated from urine is more common in non-pregnant adults,and only a small percentage have symptoms of UTI.The results of urine culture and urine routine should be comprehen-sively judged based on patient's clinical symptoms and signs.GBS in urine is susceptible to multiple antimicrobial agents,and clinical medication should be adopted rationally based on antimicrobial susceptibility testing result.
8.A multicenter study of neonatal stroke in Shenzhen,China
Li-Xiu SHI ; Jin-Xing FENG ; Yan-Fang WEI ; Xin-Ru LU ; Yu-Xi ZHANG ; Lin-Ying YANG ; Sheng-Nan HE ; Pei-Juan CHEN ; Jing HAN ; Cheng CHEN ; Hui-Ying TU ; Zhang-Bin YU ; Jin-Jie HUANG ; Shu-Juan ZENG ; Wan-Ling CHEN ; Ying LIU ; Yan-Ping GUO ; Jiao-Yu MAO ; Xiao-Dong LI ; Qian-Shen ZHANG ; Zhi-Li XIE ; Mei-Ying HUANG ; Kun-Shan YAN ; Er-Ya YING ; Jun CHEN ; Yan-Rong WANG ; Ya-Ping LIU ; Bo SONG ; Hua-Yan LIU ; Xiao-Dong XIAO ; Hong TANG ; Yu-Na WANG ; Yin-Sha CAI ; Qi LONG ; Han-Qiang XU ; Hui-Zhan WANG ; Qian SUN ; Fang HAN ; Rui-Biao ZHANG ; Chuan-Zhong YANG ; Lei DOU ; Hui-Ju SHI ; Rui WANG ; Ping JIANG ; Shenzhen Neonatal Data Network
Chinese Journal of Contemporary Pediatrics 2024;26(5):450-455
Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75%(27/36);boys accounted for 64%(23/36).Among the 36 neonates,31(86%)had disease onset within 3 days after birth,and 19(53%)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61%)had left cerebral infarction and 13(36%)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75%)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72%)and seizures in 10 neonates(34%).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33%,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44%(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.
9.Role of miR-27a-3p/PSEN1 in sevoflurane induced neurocognitive dysfunction
Jing HAN ; Ya-Hui WAN ; Xiao-Xia YANG ; Xiao-Juan YAO ; Yan CHENG
The Chinese Journal of Clinical Pharmacology 2024;40(11):1583-1587
Objective To investigate the role of miR-27a-3p in sevoflurane-induced neurocognitive dysfunction.Methods Bioinformatics prediction and validation:Predicted the target genes of miR-27a-3p using bioinformatics databases,and verified the interaction between miR-27a-3p and target genes using dual-luciferase reporter gene assay and Western blot.Cell experiments:Cells were divided into two groups,the miR-27a-3p interference control(Sevo+NC)group was transfected with miR-27a-3p interference control plasmid,and the miR-27a-3p interference treatment(Sevo+anti-miR-27a-3p)group was transfected with miR-27a-3p interference plasmid.Before transfection,the plasmids were treated with 4%sevoflurane for 6 h.Western blot was used to detect the protein expression levels of tau and phosphorylaed tau(p-tau)in SY5Y cells of each group.Animal experiments:Mice were randomly divided into control group(no treatment),sevoflurane group(treated with 4%sevoflurane only),miR-27a-3p interference control group(Sevo+NC,injected with miR-27a-3p interference control plasmid after 4%sevoflurane treatment)and miR-27a-3p interference treatment group(Sevo+anti-miR-27-3p,injected with miR-27a-3p interference plasmid after 4%sevoflurane treatment).The neurocognitive abilities of mice were tested using the water maze experiment,and the level of tau phosphorylation in the hippocampal tissue of mice was detected by immunofluorescence.Results Bioinformatics prediction and validation:Bioinformatics prediction suggested that presenilin 1(PSEN1)might be a target gene of miR-27 a-3p.Dual-luciferase reporter gene assay and Western blot showed that miR-27 a-3p interacted with PSEN1.Cell experiments:The levels of p-tau in Sevo+NC group and Sevo+anti-miR27-3p group were 0.69±0.08 and 0.21±0.05,respectively.Animal experiments:The escape latency times of the control group,sevoflurane group,Sevo+NC group and Sevo+anti-miR-27-3p group were(27.54±3.67),(52.38±6.12),(55.16±5.79)and(38.46±4.78)s,respectively;the results of the novel object exploration index were 0.78±0.11,0.31±0.07,0.33±0.06,and 0.57±0.08,respectively.Immunofluorescence detection showed a significant decrease in p-tau levels in the hippocampal tissue of mice(P<0.05).Conclusion miR-27 a-3p regulates the p-tau protein by targeting the PSEN1 gene,and interfering with miR-27 a-3p can alleviate sevoflurane-induced neurocognitive dysfunction in mice.
10.Standardized operational protocol for the China Human Brain Bank Consortium(2nd edition)
Xue WANG ; Zhen CHEN ; Juan-Li WU ; Nai-Li WANG ; Di ZHANG ; Juan DU ; Liang YU ; Wan-Ru DUAN ; Peng-Hao LIU ; Han-Lin ZHANG ; Can HUANG ; Yue-Shan PIAO ; Ke-Qing ZHU ; Ai-Min BAO ; Jing ZHANG ; Yi SHEN ; Chao MA ; Wen-Ying QIU ; Xiao-Jing QIAN
Acta Anatomica Sinica 2024;55(6):734-745
Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.

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