1.Danggui Shaoyaosan Regulates Nrf2/SLC7A11/GPX4 Signaling Pathway to Inhibit Ferroptosis in Rat Model of Non-alcoholic Fatty Liver Disease
Xinqiao CHU ; Yaning BIAO ; Ying GU ; Meng LI ; Tiantong JIANG ; Yuan DING ; Xiaping TAO ; Shaoli WANG ; Ziheng WEI ; Zhen LIU ; Yixin ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):35-42
ObjectiveTo investigate the effect of Danggui Shaoyaosan on ferroptosis in the rat model of non-alcoholic fatty liver disease (NAFLD) and explore the underlying mechanism based on the nuclear factor E2-related factor 2 (Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway. MethodsThe sixty SD rats were randomly grouped as follows: control, model, Yishanfu (0.144 g·kg-1), and low-, medium-, and high-dose (2.44, 4.88, and 9.76 g·kg-1, respectively) Danggui Shaoyaosan. A high-fat diet was used to establish the rat model of NAFLD. After 12 weeks of modeling, rats were treated with corresponding agents for 4 weeks. Then, the body weight and liver weight were measured, and the liver index was calculated. At the same time, serum and liver samples were collected. The levels or activities of total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Fe2+ in the serum and TC, TG, free fatty acids (FFA), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX), and Fe2+ in the liver were measured. Hematoxylin-eosin staining and oil red O staining were employed to observe the pathological changes in the liver. Immunofluorescence was used to assess the reactive oxygen species (ROS) content in the liver. Mitochondrial morphology was observed by transmission electron microscopy. The protein levels of Nrf2, SLC7A11, GPX4, transferrin receptor 1 (TFR1), and divalent metal transporter 1 (DMT1) in the liver were determined by Western blot. ResultsCompared with the control group, the model group showed increases in the body weight, liver weight, liver index, levels or activities of TC, TG, ALT, AST, and Fe2+ in the serum, levels of TC, TG, FFA, MDA, Fe2+, and ROS in the liver, and protein levels of TFR1 and DMT1 in the liver (P<0.01), and decreases in the activities of SOD, GPX and the protein levels of Nrf2, SLC7A11, and GPX4 in the liver (P<0.05, P<0.01). Meanwhile, the liver tissue in the model group presented steatosis, iron deposition, mitochondrial shrinkage, and blurred or swollen mitochondrial cristae. Compared with the model group, all doses of Danggui Shaoyaosan reduced the body weight, liver weight, liver index, levels or activities of TC, TG, ALT, AST, and Fe2+ in the serum, levels of TC, TG, FFA, MDA, Fe2+, and ROS in the liver, and protein levels of TFR1 and DMT1 in the liver (P<0.01), while increasing the activities of SOD and GPX and the protein levels of Nrf2, SLC7A11, and GPX4 in the liver (P<0.01). Furthermore, Danggui Shaoyaosan alleviated steatosis, iron deposition, and mitochondrial damage in the liver. ConclusionDanggui Shaoyaosan may inhibit lipid peroxidation and ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway to treat NAFLD.
2.LUNX gene serve as a prognostic biomarker for non-small cell lung cancer associated with immune cell infiltration
Xinran LU ; Ning WANG ; Zhiqiang LIU ; Yuexia ZHAO ; Xinqiao CAO ; Xiaojia LIU
Chinese Journal of Immunology 2024;40(6):1197-1202
Objective:To investigate whether the lung specific X protein(LUNX)gene can serve as a prognostic biomarker for non-small cell lung cancer related to immune cell infiltration.Methods:A total of 280 non-small cell lung cancer patients admitted to Hengshui People's Hospital from January 2020 to January 2023 were selected to detect the expression of LUNX gene in cancer tissue and adjacent tissues,and to analyze the relationship between LUNX gene and immune cell infiltration and prognosis survival status in the tumor microenvironment.Results:Compared with adjacent tissues,the expression level and positive rate of LUNX gene in non-small cell lung cancer tissue were increased,which were related to differentiation degree,lymph node metastasis and tumor staging(P<0.05).GEPIA database analysis showed that the LUNX gene was only slightly expressed or not expressed in other tissues,while its expression was elevated in LUAD and LUSC(P<0.05).The copy number of LUNX gene and LUNX gene were related to the level of immune cell infiltration(P<0.05).Survival analysis showed that high expression of the LUNX gene was associated with patient survival prognosis(P<0.05).Conclusion:The LUNX gene is specifically expressed in non-small cell lung cancer tissue,affecting the level of immune cell infiltration in non-small cell lung cancer,leading to an imbalance in the immune microenvironment,and is an important mechanism for causing patients prognostic death,which can be used as a prognostic biomarker for evaluating immune cell infiltration.
3.Correlation between serum Irisin,pentraxin3,metastasis-associated lung ad-enocarcinoma transcript 1 levels and the severity of diabetic retinopathy and the value of combined diagnosis
Bo LI ; Mingyuan LIU ; Xing LI ; Xinqiao ZHANG ; Tingting CAO ; Xi WANG ; Zhaoxia LI ; Ling BAI
Recent Advances in Ophthalmology 2024;44(6):470-475
Objective To investigate the correlation between serum Irisin,long pentraxin 3(PTX3),human metas-tasis-associated lung adenocarcinoma transcript 1(MALAT1)levels and the severity of diabetic retinopathy(DR)and the value of combined diagnosis.Methods Eighty-five patients with type 2 diabetes mellitus(T2DM)combined with DR at Cangzhou Central Hospital from April 2022 to April 2023 were selected as the DR group,85 patients with T2DM alone were selected as the non-DR group,and 85 healthy volunteers were selected as the control group during the same period.Pa-tients in the DR group were further divided into the proliferative DR(PDR)group(38 patients)and the non-PDR group(47 patients)based on whether DR was in the proliferative phase.Clinical data of patients in the DR group were collected,including gender,diastolic pressure,age,systolic pressure,disease course,fasting plasma glucose(FPG),body mass in-dex,hemoglobin A1c(HbA1c),smoking history,triglyceride(TG),drinking history,peak systolic velocity(PSV),peak end-diastolic velocity(PEDV),resistance index(RI),fasting insulin(FINS),family history of diabetes,total cholesterol(TC),and homa-insulin resistance(HOMA-IR).Enzyme-linked immunosorbent assay was used to detect serum levels of Irisin and PTX3 in each group of patients,and real-time quantitative polymerase chain reaction was used to detect the ser-um level of MALAT1.The correlations between serum levels of Irisin,PTX3 and MALAT1 and the severity of DR were ana-lyzed using the Pearson correlation coefficient.The influencing factors of the DR severity were identified using the Logistic regression.The value of serum Irisin,PTX3,and MALAT1 levels in diagnosing DR alone was analyzed using the receiver operating characteristic(ROC)curve.The value of regimens containing and not containing serum Irisin,PTX3,and MAL-AT1 levels in diagnosing DR was analyzed using the ROC curve,net reclassification index(NRI),and integrated discrimina-tion improvement(IDI)index.Results The serum levels of Irisin,PTX3,and MALAT1 were compared among the three groups of patients,and the differences were statistically significant(all P<0.001).The disease course of patients in the PDR group was longer than that in the non-PDR group,the PSV,PEDV and serum Irisin level were lower than those in the non-PDR group,while the RI,FPG,HbA1c,TG,FINS,HOMA-IR,and serum PTX3 and MALAT1 levels were higher than those in the non-PDR group(all P<0.05).The serum Irisin level in DR patients was negatively correlated with the severity of DR(r=-0.512,P<0.001),while the PTX3 and MALAT1 levels were positively correlated with the severity of DR(r=0.497,0.573,both P<0.05).The Logistic regression analysis showed that the disease course,FPG,HbA1c,TG,FINS,HOMA-IR,PSV,PEDV,RI,and serum levels of Irisin,PTX3 and MALAT1 were influencing factors for the DR progression(allP<0.05).The area under the curve(AUC)of serum Irisin,PTX3,and MALAT1 levels in diagnosing DR was 0.743,0.811,and 0.773,respectively.Compared with conventional diagnostic protocols,the AUC of the new diagnostic protocol containing serum levels of Irisin,PTX3,and MALAT1 significantly increased(Z=2.708,P=0.007),and the NRI and IDI were 0.039(95%CI:0.022-0.069)and 0.026(95%CI:0.014-0.047),respectively(all P<0.05).Conclusion The serum Irisin level in DR patients decreases,while the serum PTX3 and MALAT1 levels increase,which are closely related to the severity of DR.Diagnostic plans containing serum Irisin,PTX3,and MALAT1 indicators have high diagnostic value.
4.Incidence and recovery of nonalcoholic fatty liver disease among residents aged 65 years old and above in Xinqiao Town, Songjiang District, Shanghai
Xinxing LIANG ; Jinghong PENG ; Yiling WU ; Genming ZHAO ; Yonggen JIANG ; Yunhui WANG ; Xing LIU
Shanghai Journal of Preventive Medicine 2024;36(8):793-801
ObjectiveTo analyze the incidence, recovery rate and associated factors of nonalcoholic fatty liver disease (NAFLD) among residents aged 65 years old and above in Xinqiao Community of Songjiang, Shanghai, and to provide basic data for further efficient community management. MethodsData of annual geriatric physical examination program for residents aged 65 and above were collected in Xinqiao Community, Songjiang from 2016 to 2022. Those residents who participated twice or more were included in this analysis. Data were collated into longitudinal form. For each participant, data of the first physical examination was used as baseline, and each subsequent examination was taken as follow-up. Incidence and recovery rate of NAFLD were calculated. Cox proportional hazard models were used to explore the associated factors and their changes with the onset and recovery of NAFLD. ResultsDuring the study period, a total of 11 983 residents participated in physical examinations, of which 8 644 participated twice or more, and 8 154 had no history of excessive alcohol consumption. B-ultrasound showed that there were 5 267 residents without NAFLD and 2 887 with NAFLD at baseline. After a median follow-up of 3.3 years, the incidence density of NAFLD in this population was estimated to be 11.5 per 100 person-years, and the recovery density was 23.4 per 100 person-years. The incidence density of NAFLD was negatively associated with age, and positively associated with baseline BMI, abdominal obesity, high fasting blood glucose, and high triglycerides. The recovery density was negatively associated with baseline BMI and abdominal obesity. Compared with those with normal BMI at both baseline and follow-up, those with persistent obesity showed the highest risk of NAFLD (males: HR: 3.19, 95%CI: 2.16-4.70; females: HR: 3.34, 95%CI: 2.46-4.54) and the lowest potential of recovery (males: HR: 0.58, 95%CI: 0.42-0.82; females: HR: 0.58, 95%CI: 0.44-0.77). Persistently high triglycerides were also associated with a higher risk of developing the disease. ConclusionResidents aged 65 years old and above in Xinqiao, Shanghai had a higher incidence and recovery rate of NAFLD. Women, being obese and having hyperlipidemia are at a higher risk for the development and persistence of NAFLD.
5.Differences in Clinical Characteristics and Surgical Outcomes of Patients with Ischemic and Hemorrhagic Pituitary Adenomas
Jingpeng LIU ; Peng HUANG ; Xiaoqing ZHANG ; Yong CHEN ; Xin ZHENG ; Rufei SHEN ; Xuefeng TANG ; Hui YANG ; Song LI
Journal of Korean Neurosurgical Society 2023;66(1):72-81
Objective:
: Ischemia and hemorrhage of pituitary adenomas (PA) caused important clinical syndrome. However, the differences on clinical characteristics and surgical outcomes between these two kinds apoplexy were less reported.
Methods:
: A retrospective analysis was made of patients with pituitary apoplexy between January 2013 and June 2018. Baseline and clinical characteristics before surgery were reviewed. All patients underwent transsphenoidal surgery and were followed up at least 1 year.
Results:
: Total 67 cases (5.8%) among 1147 pituitary tumor patients were enrolled, which consisted of 28 (~2.4%) ischemic PA and 39 (~3.4%) hemorrhagic PA. There were more male patients in the ischemic group compared with hemorrhagic group (78.6% vs 53.8%, p=0.043). However, the mean age, tumor size and functional tumor ratio were significant higher in the hemorrhagic group. Headache was more common in ischemic PA (82.1%) than that of hemorrhagic PA (51.3%, p=0.011). Magnetic resonance imaging findings found that mucosal thickening and enhancement of the sphenoid sinus was observed in 15 ischemic PA patients (n=27, 55.6%), but none in patients with hemorrhagic PA (n=38, p<0.0001). It was worth noting that the rate of pre-surgical hypopituitarism in ischemic PA patients were seemed higher than that in hemorrhagic PA patients, but not significant. The two groups got a total tumor resection rate at 94.1% and 92.9%, independently. No significant difference on the operative time, blood loss in operation and complications in perioperative period was observed in two groups. After operation, cranial nerve symptoms recovered to normal at 81.8% of ischemic PA patients and 82.6% of hemorrhagic PA patients. Importantly, the incidence of postoperative hypopituitarism partially decreased in both groups, among which the rate of hypothyroidism in ischemic PA patients significantly decreased from 46.4% to 18.5% (p=0.044).
Conclusion
: Patients with ischemic PA presented different clinical characteristics to the hemorrhagic ones. Transsphenoidal surgery should be considered for the patients with neuro-ophthalmic deficits and might benefit for pituitary function recovery of the apoplectic adenoma patients, especially pituitary thyroid axis in ischemic PA patients.
6.Regulation of Danshen Zexie Decoction on AMPK/Nrf2 Signaling Pathway in Rats with Metabolic-associated Fatty Liver Disease
Yaning BIAO ; Xinqiao CHU ; Muqing ZHANG ; Chenxu LIU ; Cheng SHI ; Sitong LI ; Yixin ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(1):67-74
ObjectiveTo explore the efficacy and mechanism of Danshen Zexie decoction in treating the rats with metabolic-associated fatty liver disease (MAFLD). MethodSixty male SD rats were randomized into control group, model group, essentiale (polyene phosphatidylcholine capsules, 0.144 g·kg-1) group, and low-, medium-, and high-dose Danshen Zexie decoction (1.16, 2.32, and 4.64 g·kg-1, respectively) groups. The rat model of MAFLD was established with high fat diet, and 8-week therapy started at the induction of MAFLD. The serum levels of total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), as well as the liver levels of TC, TG, free fatty acid (FFA), superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA), were measured. The pathological changes of liver were observed by hematoxylin-eosin (HE) staining and oil red O staining, and the steatosis score and oil red O staining area were calculated. The level of reactive oxygen species (ROS) in the liver was detected by immunofluorescence. The protein levels of adenosine monophosphate-activated protein kinase (AMPK), p-AMPK, nuclear factor E2-related factor 2 (Nrf2), glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase modifier subunit (GCLM), and nicotinamide adenine dinucleotide phosphate: quinine oxidoreductase (NQO1) in the liver were determined by Western blot. ResultCompared with control group, the modeling of MAFLD elevated the levels of TC, TG, ALT, and AST in the serum and TC, TG, FFA, MDA, and ROS in the liver (P<0.01), lowered the levels of SOD and GSH and down-regulated the protein levels of phosphorylation(p)-AMPK, Nrf2, GCLC, GCLM, and NQO1 in the liver (P<0.05, P<0.01). Further, a large number of lipid droplet vacuoles and balloon-like lesions appeared in the hepatocytes, and the steatosis score and oil red O staining area increased in the model group (P<0.01). Compared with model group, Danshen Zexie decoction lowered the levels of TC, TG, ALT, and AST in the serum and TC, TG, FFA, MDA, and ROS in the liver (P<0.01), increased the levels of SOD and GSH and up-regulated the protein levels of p-AMPK, Nrf2, GCLC, GCLM, and NQO1 in the liver (P<0.05, P<0.01). Moreover, the decoction alleviated the degree of liver steatosis (P<0.05, P<0.01). ConclusionDanshen Zexie decoction protects against MAFLD by activating AMPK/Nrf2 signaling pathway and suppressing oxidative stress.
7.Systematic evaluation of acute herpes zoster treatment with fire needle therapy mainly
Xinqiao CHU ; Hongmei LIU ; Yufeng GUO ; Ning GAO ; Peichu ZHANG ; Yingxin SUN
International Journal of Traditional Chinese Medicine 2023;45(10):1307-1312
Objective:To systematically evaluate the clinical efficacy of fire needle therapy and conventional western medicine in the treatment of patients with acute herpes zoster.Methods:Randomized controlled trials (RCTs) of fire needle therapy in the treatment of acute herpes zoster were retrieved from China National Knowledge Internet (CNKI), Wanfang, Database of Chinese Sci Tech Periodicals (VIP Database), China Biomedical Literature Database (CBM), Medline, Embase, and Cochrane Library from the establishment of the databases to May 30, 2022. According to the inclusion and exclusion criteria, the included literature was screened, and Review Manager 5.3 was used for system evaluation and meta-analysis.Results:7 articles were included for analysis after screening, involving 452 patients. There were 226 cases in the treatment group and 226 cases in the control group. The results of meta-analysis showed that fire needle therapy was superior to conventional western medicine in the total effective rate [ RR=0.36, 95% CI (0.20, 0.65), P=0.000 7], lower incidence of PHN [ RR=0.25, 95% CI (0.09, 0.72), P=0.01], lower VAS score [ MD=-1.19, 95% CI (-2.14, -0.24), P=0.01], and shorter scab forming time [ MD=-2.03, 95% CI (-2.42, -1.64), P<0.001]. Conclusion:The curative effect of fire needle therapy is more prominent than that of conventional western medicine in the treatment of acute herpes zoster.
8.Evaluation of abnormalities in right atrial volume and function in patients with pulmonary hypertension by four-dimensional ultrasound automatic quantitation analysis
Yinqi SONG ; Zhe CHEN ; Min LIU ; Yulei MA ; Xing FANG ; Jiangtao CHENG ; Xinqiao TIAN
Chinese Journal of Ultrasonography 2023;32(11):977-984
Objective:To evaluate the right atrial volume and function abnormalities in patients with pulmonary hypertension (PH) by four-dimensional automatic quantitation technique, and to explore the application value of this technique in evaluating the risk stratification and World Health Organization functional class(WHO-FC) of PH patients.Methods:Eighty-four adult patients with PH diagnosed by right heart catheterization from April to October 2022 in Fuwai Central China Cardiovascular Hospital were consecutively enrolled as the PH group. All cases were divided into 3 groups according to the mean pulmonary arterial pressure (mPAP): mild PH group ( n=28), moderate PH group ( n=28), severe PH group ( n=28). Twenty-eight healthy volunteers matched by gender and age were included in the same period as the control group. The volume and strain parameters of the right atrium were obtained by analyzing the four-dimensional image of the right atrium using four-dimensional automatic quantitation technique, including right atrial minimum volume index (RAVImin), right atrial maximum volume index (RAVImax), right atrial presystolic volume index (RAVIpreA), right atrial ejection fraction (RAEF), right atrial passive ejection fraction (RAPEF), right atrial active ejection fraction, RAAEF, longitudinal strains of right atrial reserve, conduit and systolic period (RASr, RAScd, RASct), circumferential strains of right atrial reserve, conduit and systolic period (RASr-c, RAScd-c, RASct-c). The differences in right atrial parameters among four groups were compared.ROC curve was used to analyze the diagnostic efficiency of right atrial four-dimensional strain parameters for PH patients with WHO-FC≥Ⅲ. Pearson linear correlation analysis was used to investigate the relationships between RASr and right atrial area (RAA), NT-proBNP and tricuspid annular plane systolic excursion to pulmonary arterial systolic pressure ratio (TAPSE/sPAP). Results:①Compared with the control group, RAEF, RAPEF, RASr, RAScd, RASr-c, RAScd-c were significantly decreased in mild, moderate and severe PH groups; while RAAEF, RASct, RASct-c were significantly increased in mild PH group and significantly decreased in moderate and severe PH groups, and the differences were statistically significant (all P<0.05). RAVImin, RAVImax, RAVIpreA gradually increased among the control, mild PH, moderate PH and severe PH groups, and the differences were statistically significant (all P<0.05). RAEF, RAPEF, RAAEF, RASr, RAScd, RASct, RASr-c, RAScd-c, RASct-c were decreased successively among mild, moderate and severe PH groups, and the differences were statistically significant (all P<0.05). ②ROC curve showed that RASr had the highest diagnostic efficiency in PH patients with WHO-FC ≥Ⅲ, and the cut-off value was 20.5% (AUC=0.914, P<0.001). ③Correlation analysis showed that RASr was correlated with RAA, NT-proBNP and TAPSE/sPAP ( r=-0.803, -0.621, 0.739; all P<0.001). Conclusions:The degree of right atrial function impairment increased in patients with mild, moderate and severe PH in turn. RASr is the best predictor of WHO-FC ≥Ⅲ in patients with pulmonary hypertension and is a potential parameter for risk stratification in patients with PH.
9. Dicer requiring for astrocyte quiescence in developing brains
Kun LIU ; Jing-Fei CHEN ; Shou-Yu WANG ; Tao LI ; Feng MEI ; Lan XIAO ; Bin YU ; Feng MEI ; Lan XIAO ; Xing GAO
Acta Anatomica Sinica 2022;53(4):407-411
Objective To explore whether microRNAs (miRNA) in astrocytes participate in regulating the phenotypic switch in the developing central nervous system (CNS). Methods The hGFAP-CreERT; Dicer fl/fl; mT/mG and Dicer fl/fl; mT/mG mice were generated and induced by tamoxifen (TMF). The)' were divided into 7 days, 10 days, 14 days Dicer conditional knock out (Dicer CKO) group and control group according to their age and the expression of hGFAP-CreERT. These 24 mice were divided into six groups and each group contained four mice. Then the change of astrocytes in the developing CNS was observed by immunofluorescenct staining. Results Both of the densities of astrocytes and microglial cells increased in the Dicer CKO mice brains as compared to littermate controls. Conclusion Dicer and miRNA of astrocytes are important for astrocytes quiescence in developing brains.
10.Molecular mechanism of Yueju Pill for the treatment of functional dyspepsia based on network pharmacology and molecular docking
Yaru GU ; Xinqiao CHU ; Yue WANG ; Yaning BIAO ; Chenxu LIU ; Yixin ZHANG ; Congkun XIANG
International Journal of Traditional Chinese Medicine 2022;44(9):1028-1036
Objective:To discuss the mechanism of Yueju Pill in the treatment of functional dyspepsia (FD) based on network pharmacology and molecular docking.Methods:The chemical components and action targets of Yueju Pill were screened out by TCMSP platform and HERB, BATMAN-TCM database combined with literature were used to supplement effective components of Vietnam bow. The targets of FD were screened out by GeneCards database and OMIM database, and the intersection of the two targets was used to analyze the protein interactions using the STRING platform to construct the PPI network. Metascape platform was used for GO and KEGG pathway enrichment analysis, and Cytoscape 3.7.2 software was used to construct a network of "Yueju Pill components-functional dyspepsia targets-pathways". Online mapping tools were used to obtain the Venn plot of the intersection targets of Yueju Pill, FD and its related pathogenesis. Finally, AutoDock software was used for molecular docking.Results:The main active components of Yueju Pill in the treatment of FD are quercetin, wogonin, luteolin, kaempferol, etc. The main targets are AKT1, MAPK1, JUN, RELA, IL6, BCL2, BAX, MAPK8, EGFR, ESR1, etc. Molecular docking shows that the targets and the active components of the Yueju Pill have better binding abilit. The GO enrichment analysis result shows that there are 2 273 biological processes, 152 molecular functions and 91 cell components. KEGG enrichment analysis shows that there are 344 pathways associated with FD. According to literature review, the pathways related to FD include PI3K-Akt signaling pathway, AGE-RAGE signaling pathway, IL-17 signaling pathway, etc.Conclusion:Yueju Pill might act on AKT1, MAPK1, JUN, RELA, IL6, BCL2, BAX, MAPK8, EGFR, ESR1 and other targets to regulate PI3K-Akt signaling pathway, AGE-RAGE signaling pathways and IL-17 signaling pathway and it could treat FD.

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