1.Vulnerability of medicinal plant Lamiophlomis rotata  under future climate changes
		                			
		                			Hong-chao WANG ; Zheng-wei XIE ; Qi-ao MA ; Tie-lin WANG ; Guang YANG ; Xiao-ting XU ; Kai SUN ; Xiu-lian CHI
Acta Pharmaceutica Sinica 2024;59(10):2871-2879
		                        		
		                        			
		                        			 italic>Lamiophlomis rotata is an important medicinal plant species endemic to the Tibetan Plateau, which is prone to strong climate change impacts on its habitable range due to the high sensitivity of the Tibetan Plateau to climate change. Accurate quantification of species vulnerability to climate change is essential for assessing species extinction risk and developing effective conservation strategies. Therefore, we carried out the 
		                        		
		                        	
2.Epidemiological characteristics of imported malaria after malaria elimination in Shanxi Province, 2019-2023
Ting WANG ; Ping TIE ; Yongfei BAI ; Yuhua ZHENG ; Jingying WANG
Chinese Journal of Epidemiology 2024;45(10):1390-1395
		                        		
		                        			
		                        			Objective:To analyze the epidemiological characteristics of imported malaria cases from 2019 to 2023 after the elimination of malaria in Shanxi Province, and provide reference for formulating scientific and effective malaria prevention and control strategies in Shanxi Province.Methods:The data of imported malaria cases were collected China Information System for Disease Control and Prevention and National Parasitic Disease Control Information Management System in Shanxi Province, from 2019-2023. Descriptive epidemiological method and SPSS 26.0 statistical software were used for descriptive epidemiological statistical analysis.Results:A total of 51 malaria cases were reported in Shanxi Province in 2019-2023, all imported from abroad. Among them, there were 38 cases of falciparum malaria (74.51%), 6 cases of plasmodium ovale (11.77%), 5 cases of plasmodium vivax (9.80%), 1 case of plasmodium triticum malaria (1.96%), and 1 case of mixed infections (1.96%), with nodeaths; cases were predominantly males (94.12%, 48/51) and workers who went abroad for work (84.31%,43/51); the median age of onset was 37 years old; and there were imported cases every month, with no obvious peak of incidence; Taiyuan City reported the most cases, accounting for 72.55% (37/51) of the total number of cases,the source of infection of cases was mainly from Africa (96.08%), with the Democratic Republic of the Congo (16 cases), Nigeria (6 cases), Equatorial Guinea (5 cases), Mozambique (3 cases), and Republic of the Congo (3 cases) in that order; the median time between the onset of disease and first diagnosis, and the median time between first diagnosis and confirmation, were two times longer than that of first diagnosis, and the median time between first diagnosis and confirmation was two times longer than that of first diagnosis. The M( Q1, Q3) intervals from onset to first diagnosis and from first diagnosis to confirmed diagnosis were 2(0,4) days and 1(0,3) days, respectively, with statistically significant differences between different years from onset to first diagnosis ( H=17.41, P=0.048), and from first diagnosis to confirmed diagnosis ( H=20.82, P=0.010). A total of 101 146 blood tests for febrile patients were conducted in the province during the five years, with the minimum number of blood tests in 2020 (19 867 person-times) and the maximum number of blood tests in 2023 (20 778 person-times). Conclusions:After the elimination of malaria in Shanxi Province from 2019 to 2023, all malaria cases were imported from abroad, and it is still necessary to strengthen the surveillance of people traveling to and from malaria-endemic areas, implement the combination of medical treatment and prevention, and jointly prevent and control the occurrence of imported malaria.
		                        		
		                        		
		                        		
		                        	
3.Study on the antidepressant mechanism of ginseng-fragrant solomonseal rhizome couplet medicines on inhibiting the activation of inflammasomes NLRP1,NLRC4,and AIM2,and regulating the expression of inflammatory cytokines
Huayu ZHANG ; Jialu CAO ; Bingyuan ZHENG ; Qian LIU ; Ke LIANG ; Tie QIAO
Journal of Beijing University of Traditional Chinese Medicine 2024;47(7):939-947
		                        		
		                        			
		                        			Objective To observe the effect of Renshen(ginseng)-Yuzhu(fragrant solomonseal rhizome)on inflammatory factors and inflammasomes in depression rats,and to explore the antidepressant mechanism of Renshen-Yuzhu.Methods Fifty male SD rats were divided into the blank group,model group,fluoxetine group(2.1 mg/kg),Renshen-Yuzhu low-dose group(1.89 g/kg),and Renshen-Yuzhu high-dose group(5.67 g/kg),with ten rats in each group.Except for the blank group,the rats in the other groups were treated with chronic unpredictable mild stress to establish a depression rat model.On the second day after the end of modeling,the rats in each group were given the corresponding drugs once daily for 14 days.After modeling and dosing,body weight,forced swimming immobility time,and sucrose preference rate were measured.After dosing,hematoxylin-eosin staining was used to detect neuronal damage in the cerebral cortex,enzyme-linked immunosorbent assay was used to detect the contents of interleukin-4(IL-4),interleukin-23(IL-23),and interleukin-27(IL-27)in cortex,real-time PCR was used to detect the mRNA expression of interleukin-24(IL-24)in cortex,and the protein expressions of nucleotide-binding oligomerization domain-like receptor protein 1(NLRP1),absent in melanoma 2(AIM2),and nucleotide-binding oligomerization domain-like receptor protein 4(NLRC4)were detected by Western blotting.Results After dosing,compared with the blank group,the body weight of the model group decreased,the sucrose preference rate decreased,the swimming immobility time was prolonged,the neuronal tissue in cortex was destroyed,the content of IL-4 in cortex decreased,the contents of IL-23 and IL-27 in cortex increased,and the protein expressions of NLRP1,AIM2 and NLRC4 in cortex increased(P<0.01).Compared with the model group,the body weight of rats in each administration group increased,the sucrose preference rate increased,the swimming immobility time was shortened,the damage of neuronal tissues in cortex improved,the content of IL-4 in cortex increased,the contents of IL-23 and IL-27 in cortex decreased,and the protein expressions of NLRP 1,AIM2 and NLRC4 in cortex decreased(P<0.05).Conclusion Renshen-Yuzhu couplet medicines can improve the depressive-like behavior and exert antidepressant effect in chronic stress rats,and its mechanism may be related to the inhibition of NLRP 1,NLRC4,AIM2 inflammasome activation and its mediated inflammatory response in cortex,reducing pro-inflammatory cytokines,and increasing the level of antiinflammatory cytokines.
		                        		
		                        		
		                        		
		                        	
4.Progress in study of multifunctionality of DPP4 and mechanism of action of related drug targets
Lei WANG ; Zhi-Hui YANG ; Yang ZHENG ; Ying ZHANG ; Tie-Jian ZHAO ; Wei-Sheng LUO ; Tian-Jian LIANG ; Jia-Hui WANG
Chinese Pharmacological Bulletin 2024;40(12):2212-2217
		                        		
		                        			
		                        			DPP4 is a serine exopeptidase that is immobilized on the cell membrane and plays a crucial regulatory role in various physiological and pathological activities within the human body.In addition to acting as a transcription factor to regulate the tran-scription and expression of downstream target genes,DPP4 also functions as a transcription-independent regulator through pro-tein-protein interactions.In recent studies,DPP4 has been strongly linked to various diseases,and several substances with the potential to target DPP4 have been identified.This paper mainly reviews the multifunctionality of DPP4 in regulating vari-ous aspects of energy metabolism,inflammation,tissue repair and carcinogenesis in the body.It also reviews the screening of in vitro inhibitors of DPP4 and its research progress in regulating chronic liver disease,based on the pathological development process of chronic liver disease.
		                        		
		                        		
		                        		
		                        	
5.Effects of curcumol on iron death and epithelial-mesenchymal transition in hepatic stellate cells
Lei WANG ; Jin-Biao HUANG ; Yan-Qing HUANG ; Ze-Yu WANG ; Jia-Hui WANG ; Yang ZHENG ; Wei-Sheng LUO ; Tie-Jian ZHAO
The Chinese Journal of Clinical Pharmacology 2024;40(4):539-543
		                        		
		                        			
		                        			Objective To elucidate the effect of curcumol on hepatic stellate cell iron death and epithelial-mesenchymal transition(EMT),and to investigate the molecular mechanism of its anti-liver fibrosis effect.Methods A model of hepatic stellate cell activation was constructed using normal cultured hepatic stellate cells in vitro,and the cells were divided into blank group and experimental-L,-M,-H groups.The blank group was given DMEM complete culture solution for normal culture;the experimental-L,-M,-H groups were given DMEM complete culture solution containing 12.5,25.0 and 50.0 mg·L-1 curcumol for 48 h of intervention.The effects of curcumol on the proliferation of hepatic stellate cells was observed by CCK-8.The expression levels of glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)were detected by Western blot.The expression levels of E-cadherin and N-cadherin were detected by immunofluorescence.Results The cell proliferation rates of the experimental-M,-H groups and blank group were(68.97±5.61)%,(61.91±4.40)%and(118.07±10.01)%;the relative expression levels of GPX4 were 0.37±0.04,0.28±0.03 and 0.58±0.05;the relative expression levels of SLC7A11 were 0.38±0.04,0.28±0.03 and 0.60±0.05;E-cadherin levels were 6.76±1.09,9.57±1.73 and 2.05±0.72;N-cadherin levels were 5.66±0.66,3.44±0.78 and 10.37±0.66.The differences of above indicators were statistically significant between the blank group and the experimental-M,-H groups(P<0.05,P<0.01).Conclusion Curcumol promotes iron death in hepatic stellate cells,thereby inhibiting hepatic stellate cell EMT,which may be its molecular mechanism to prevent and treat liver fibrosis.
		                        		
		                        		
		                        		
		                        	
6.Risk factors associated with neovascular glaucoma after vitrectomy for proliferative diabetic retinopathy
Xue ZU ; Guang-Zheng DAI ; Tie-Zhu LIN
International Eye Science 2023;23(5):808-812
		                        		
		                        			
		                        			 AIM: To investigate the risk factors associated with neovascular glaucoma(NVG)after pars plana vitrectomy(PPV)for proliferative diabetic retinopathy(PDR).METHODS: The PDR patients who received 23G PPV treatment at Shenyang He Eye Specialist Hospital from October 2015 to September 2020 and were followed up for at least 12mo with complete data were retrospectively collected. The patients were divided into two groups according to the occurrence of NVG during follow-up. The preoperative and intraoperative variables between two groups were compared. The cumulative hazard ratio for NVG was evaluated. RESULTS: A total of 151 PDR patients(169 eyes)with a mean follow-up of 18.07±12.55(1~79)mo were included, of which 30(17.8%)eyes developed NVG, the mean time of occurrence was 6.27±4.01(1~17)mo, and 50%(15 eyes)of NVG occurred within 5mo after vitrectomy. The cumulative hazard ratios of NVG at postoperative 3, 6 and 12mo were 4.8%, 12.6% and 18.1%, respectively. Multivariate logistic regression analysis showed that preoperative best corrected visual acuity(OR=3.077, 95%CI: 1.203~7.869, P=0.019), preoperative iris rubeosis(OR=7.897, 95%CI: 1.313~47.498, P=0.024), and contralateral NVG(OR=22.108, 95%CI: 1.562~312.861, P=0.022)were risk factors with the occurrence of NVG, while the number of intraoperative retinal laser photocoagulation(OR=0.772, 95%CI: 0.666~0.893, P=0.001)was the protective factor with the occurrence of NVG.CONCLUSIONS: The incidence of NVG in PDR eyes after PPV was 17.8%, of which 50% occurred within 5mo after surgery. PDR eyes with poor baseline visual acuity, iris rubeosis, and contralateral NVG are prone to postoperative NVG, and sufficient intraoperative retinal laser photocoagulation has a certain protective effect. PDR eyes after PPV should be closely followed up for 1a. 
		                        		
		                        		
		                        		
		                        	
7.Risk factors for neonatal asphyxia and establishment of a nomogram model for predicting neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture: a multicenter study.
Fang JIN ; Yu CHEN ; Yi-Xun LIU ; Su-Ying WU ; Chao-Ce FANG ; Yong-Fang ZHANG ; Lu ZHENG ; Li-Fang ZHANG ; Xiao-Dong SONG ; Hong XIA ; Er-Ming CHEN ; Xiao-Qin RAO ; Guang-Quan CHEN ; Qiong YI ; Yan HU ; Lang JIANG ; Jing LI ; Qing-Wei PANG ; Chong YOU ; Bi-Xia CHENG ; Zhang-Hua TAN ; Ya-Juan TAN ; Ding ZHANG ; Tie-Sheng YU ; Jian RAO ; Yi-Dan LIANG ; Shi-Wen XIA
Chinese Journal of Contemporary Pediatrics 2023;25(7):697-704
		                        		
		                        			OBJECTIVES:
		                        			To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia.
		                        		
		                        			METHODS:
		                        			A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively.
		                        		
		                        			RESULTS:
		                        			Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia.
		                        		
		                        			CONCLUSIONS
		                        			The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
		                        		
		                        		
		                        		
		                        			Infant, Newborn
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		                        			Humans
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		                        			Male
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		                        			Pregnancy
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		                        			Female
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		                        			Nomograms
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		                        			Retrospective Studies
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		                        			Cesarean Section
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		                        			Risk Factors
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		                        			Asphyxia Neonatorum/etiology*
		                        			
		                        		
		                        	
8.Yinlai Decoction Protects Microstructure of Colon and Regulates Serum Level of D-Lactic Acid in Pneumonia Mice Fed with High-Calorie and High-Protein Diet.
Yun-Hui WANG ; He YU ; Tie-Gang LIU ; Teck Chuan KONG ; Zi-An ZHENG ; Yu-Xiang WAN ; Chen BAI ; Yu HAO ; Ying-Qiu MAO ; Jun WU ; Jing-Nan XU ; Li-Jun CUI ; Yu-Han WANG ; Yan-Ran SHAN ; Ying-Jun SHAO ; Xiao-Hong GU
Chinese journal of integrative medicine 2023;29(8):714-720
		                        		
		                        			OBJECTIVE:
		                        			To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD).
		                        		
		                        			METHODS:
		                        			Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice.
		                        		
		                        			RESULTS:
		                        			The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05).
		                        		
		                        			CONCLUSIONS
		                        			YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.
		                        		
		                        		
		                        		
		                        			Mice
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		                        			Male
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		                        			Animals
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		                        			Lactic Acid/pharmacology*
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		                        			Intestinal Mucosa
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		                        			Colon/pathology*
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		                        			Dexamethasone/pharmacology*
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		                        			Diet, High-Protein
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		                        			Pneumonia/pathology*
		                        			
		                        		
		                        	
9.Panax notoginseng saponins improve monocrotaline-induced pulmonary arterial hypertension in rats by inhibiting ADAM10/Notch3 signaling pathway.
Sai ZHANG ; Yun-Na TIAN ; Zheng-Yang SONG ; Xiao-Ting WANG ; Xin-Yu WANG ; Jun-Peng XU ; Lin-Bo YUAN ; Wan-Tie WANG
Acta Physiologica Sinica 2023;75(4):503-511
		                        		
		                        			
		                        			In this study, we investigated the effects of Panax notoginseng saponins (PNS) on pulmonary vascular remodeling and ADAM10/Notch3 pathway in pulmonary arterial hypertension (PAH). PAH rat model was established, and male Sprague Dawley (SD) rats were randomly divided into control group, monocrotaline (MCT) group and MCT+PNS group, with 10 rats in each group. Rats in the control group were intraperitoneally injected with equal volume of normal saline. Rats in the MCT group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with the same volume of normal saline every day. Rats in the MCT+PNS group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with 50 mg/kg PNS every day. The modeling time of each group lasted for 21 days. After the model was established, the mean pulmonary artery pressure (mPAP) was measured by right heart catheterization technique, the right ventricular hypertrophy index (RVHI) was calculated, the microscopic morphology and changes of pulmonary vascular wall were observed by HE and Masson staining, and the expressions of ADAM10, Notch3, Hes-1, P27, PCNA, Caspase-3 proteins and mRNA in pulmonary vascular tissue of rats were detected by Western blot and qPCR. The expression and localization of Notch3 and α-SMA were detected by immunofluorescence staining. The protein expression of ADAM10 was detected by immunohistochemical staining. The results showed that compared with the control group, mPAP, RVHI, pulmonary vessels and collagen fibers in the MCT group were significantly increased, the expressions of ADAM10, Notch3, Hes-1, and PCNA protein and mRNA were significantly increased, while the expressions of P27 and Caspase-3 protein and mRNA were decreased significantly. Compared with the MCT group, mPAP and RVHI were significantly decreased, pulmonary vessels were significantly improved and collagen fibers were significantly reduced, the expressions of protein and mRNA of ADAM10, Notch3, Hes-1, and PCNA were decreased in MCT+PNS group, but the expressions of protein and mRNA of P27 and Caspase-3 were increased slightly. The results of immunofluorescence showed that Notch3 and α-SMA staining could overlap, which proved that Notch3 was expressed in smooth muscle cells. The expression of Notch3 in the MCT group was increased significantly compared with that in the control group, while PNS intervention decreased the expression of Notch3. Immunohistochemical staining showed that compared with the control group, the amount of ADAM10 in the MCT group was increased significantly, and the expression of ADAM10 in the MCT+PNS group was decreased compared with the MCT group. These results indicate that PNS can improve the PAH induced by MCT in rats by inhibiting ADAM10/Notch3 signaling pathway.
		                        		
		                        		
		                        		
		                        			Animals
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		                        			Male
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		                        			Rats
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		                        			Caspase 3/metabolism*
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		                        			Collagen
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		                        			Disease Models, Animal
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		                        			Hypertension, Pulmonary/drug therapy*
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		                        			Monocrotaline/adverse effects*
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		                        			Panax notoginseng/chemistry*
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		                        			Proliferating Cell Nuclear Antigen/pharmacology*
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		                        			Pulmonary Arterial Hypertension
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		                        			Pulmonary Artery/metabolism*
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		                        			Rats, Sprague-Dawley
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		                        			Receptor, Notch3/genetics*
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		                        			RNA, Messenger
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		                        			Saline Solution
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		                        			Signal Transduction
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		                        			Saponins/pharmacology*
		                        			
		                        		
		                        	
10.Research progress of the regulation of orphan nuclear receptors on chronic liver diseases.
Zhi-Hui YANG ; Jia-Hui WANG ; Lei WANG ; Xue-Lin DUAN ; Hong-Hong WANG ; Yue PENG ; Tie-Jian ZHAO ; Yang ZHENG
Acta Physiologica Sinica 2023;75(4):555-568
		                        		
		                        			
		                        			The development of chronic liver disease can be promoted by excessive fat accumulation, dysbiosis, viral infections and persistent inflammatory responses, which can lead to liver inflammation, fibrosis and carcinogenesis. An in-depth understanding of the etiology leading to chronic liver disease and the underlying mechanisms influencing its development can help identify potential therapeutic targets for targeted treatment. Orphan nuclear receptors (ONRs) are receptors that have no corresponding endogenous ligands to bind to them. The study of these ONRs and their biological properties has facilitated the development of synthetic ligands, which are important for investigating the effective targets for the treatment of a wide range of diseases. In recent years, it has been found that ONRs are essential for maintaining normal liver function and their dysfunction can affect a variety of liver diseases. ONRs can influence pathophysiological activities such as liver lipid metabolism, inflammatory response and cancer cell proliferation by regulating hormones/transcription factors and affecting the biological clock, oxidative stress, etc. This review focuses on the regulation of ONRs, mainly including retinoid related orphan nuclear receptors (RORs), pregnane X receptor (PXR), leukocyte cell derived chemotaxin 2 (LECT2), Nur77, and hepatocyte nuclear factor 4α (HNF4α), on the development of different types of chronic liver diseases in different ways, in order to provide useful references for the therapeutic strategies of chronic liver diseases based on the regulation of ONRs.
		                        		
		                        		
		                        		
		                        			Humans
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		                        			Orphan Nuclear Receptors/metabolism*
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		                        			Receptors, Steroid/physiology*
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		                        			Ligands
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		                        			Liver
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		                        			Liver Diseases
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		                        			Intercellular Signaling Peptides and Proteins
		                        			
		                        		
		                        	
            
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