1.CircRNA Circ_0120051 Inhibits the Fibrotic Phenotype of Myocardial Fibroblasts via Targeting miR-144-3p/IDH2 Axis
Yu LIANG ; Zhiqin HU ; Yihong WEN ; Huayan WU ; Ya WNAG ; Yupeng LIU ; Zhixin SHAN ; Xianhong FANG
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(2):196-205
ObjectiveTo investigate the regulatory effect of circular RNA circ_0120051 on the fibrotic phenotype of cardiac fibroblasts and the potential mechanism involved. MethodsThe expression of circ_0120051 and its host gene of solute carrier family 8 member A1(SLC8A1) mRNA in the myocardium of healthy organ donors (n=24) and heart failure (HF) patients (n=21) were assessed by real-time quantitative polymerase chain reaction (RT-qPCR) assay. RNA stability of circ_0120051 was identified by RNase R exonuclease digestion assay. The cytoplasmic and nuclear distribution of circ_0120051 in human cardiomyocyte AC16 was detected by RT-qPCR assay. The expression of fibrosis-related genes in mouse cardiac fibroblasts (mCFs) with adenovirus-mediated overexpression of circ_0120051 was detected by RT-qPCR and Western blot assay, respectively. The effect of overexpression of circ_0120051 on the migration activity of mCFs was evaluated by wound-healing assay. RNA co-immunoprecipitation (RIP) was conducted to detect the interaction between circ_0120051 and miR-144-3p. The binding site of miR-144-3p in the 3'-UTR of isocitrate dehydrogenase 2 (Idh2) mRNA was identified by the dual luciferase reporter gene assay. ResultsCirc_0120051 was significantly up-regulated in the myocardium of HF patients, while the mRNA expression of its host gene SLC8A1 was not changed. Circ_0120051 was mainly located in the cytoplasm of human AC16 cells. Results of RNase R exonuclease digestion revealed that circ_0120051 possesses the characteristic stability of circular RNA compared to the linear SLC8A1 mRNA. Overexpression of circ_0120051 could inhibit the expression of fibrosis-related gene in mCFs and mCFs migration. RIP assay confirmed the specific interaction between circ_0120051 and miR-144-3p. Transfection of miR-144-3p mimic could efficiently promote the expression of fibrosis-related genes in mCFs and reverse the inhibitory effect of circ_0120051 on the fibrotic phenotype of mCFs. Results of the dual luciferase reporter gene assay confirmed the interaction between miR-144-3p and the 3'-UTR of Idh2. Transfection of miR-144-3p transcriptionally inhibited Idh2 expression, and overexpression of circ_0120051 enhanced IDH2 expression in mCFs. MiR-144-3p mimic and Idh2 small interfering RNA (siRNA) could consistently reverse the inhibitory effects of circ_0120051 on fibrosis-related genes expression in mCFs and mCFs migration. ConclusionsCirc_0120051 inhibits the fibrotic phenotype of cardiac fibroblasts via sponging miR-144-3p to enhance the target gene of IDH2 expression.
2.Research on Material Basis of Homologous and Heterogeneous Effect of Aurantii Fructus Immaturus and Aurantii Fructus Based on Total Statistical Moment Analysis and Molecular Connectivity Index
Xiao YUAN ; Yuefeng WU ; Shixiong LI ; Youzhi LIU ; Zhiqin YU ; Fuyuan HE ; Jin ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):161-168
ObjectiveTo investigate the material basis of homologous and heterogeneous effect of Aurantii Fructus Immaturus(AFI) and Aurantii Fructus(AF) based on the total statistical moment analysis and molecular connectivity index(MCI). MethodRelevant literature at home and abroad and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) were consulted to establish the chemical composition database of AFI and AF, and set up their fingerprints by ultra-high performance liquid chromatography(UPLC), and the total statistical moments and similarity parameters of the fingerprint were calculated. According to MCI, all components of AFI and AF were divided into different component groups, the average values of 0-8th order(0χ-8χ) MCI of the common component groups of AFI and AF were calculated. ResultThe values of total zero-order moment(AUCT) of AFI and AF were (10.57±2.45)×106, (5.09±0.89)×106 μV·s, the values of total first-order moment(MCRTT) were (11.57±1.58), (12.10±1.29) min, the values of total second-order moments(VCRTT) were(24.49±2.30), (26.49±2.54) min2, respectively. It showed that qualitative and quantitative parameters of AFI and AF were significantly different. The components with high similarity such as neohesperidin, hesperidin and narirutin were screened as the common potential pharmacodynamic components of AFI and AF. The non-common components of AFI, such as alysifolinone and imperatorin, and the non-common components of AF, such as neoeriocitrin and isosakuranin, with high similarity were screened out as potential heterogeneous components of AFI and AF. The composition groups of AFI and AF were classified into six categories, and the similarities between the composition groups of AFI and AF and the total constituents were 0.872-0.979 and 0.918-0.997, the average values of 0χ-8χ MCI of alkaloids in AFI and AF were 3.65 and 3.14, the average values of 0χ-8χ MCI of flavonoids were 8.47 and 8.47, the average values of 0χ-8χ MCI of volatile oils were 2.71 and 3.48, respectively. It showed that there were some differences in MCI of chemical constituents(groups) between AFI and AF. ConclusionThe chemical constituents(groups) of AFI and AF not only differ in content and species, but also in structural characteristics and structure-activity relationship, which can provide a basis for further explaining the scientific connotation of homologous and heterogeneous effect of AFI and AF.
3.Arthroscopic partial trapeziectomy and suture button suspensionplasty in the treatment of first carpometacarpal joint athrosis
Zhe ZHAO ; Hongli GENG ; Jianquan LIU ; Yongsheng LI ; Jianwen YIN ; Xiaoqiang CHEN ; Guanghui WANG ; Xiangyu CHENG ; Jiabei LI ; Zhiqin DENG ; Aozhengzheng DONG ; Manyi WANG ; Xiaofei ZHENG ; Wencui LI
Chinese Journal of Orthopaedics 2024;44(1):25-32
Objective:To analyze the clinic effects of arthroscopic partial trapeziectomy and suture button suspensionplasty in the treatment of first carpometacarpal joint (CMCJ) Eaton stage II/III arthrosis.Methods:A retrospective study was conducted on a total of 15 cases (16 hands) of patients including 5 males (1 bilateral) and 10 females with CMCJ stage II/III arthrosis who underwent surgical treatment at the first affiliated hospital of Shenzhen university from January 2020 to June 2022, with mean age of 56.7±6.4 years (range, 46-75 years). The duration from pain to treatment was 7.8±3.2 months (range, 4-14 months). X-ray showed narrowing of CMCJ with osteophytes and distal radial subluxation. All the patients were treated with arthroscopic partial trapeziectomy and suture button suspensionplasty. The preoperative and last postoperative follow-up radiographs, visual analogue scale (VAS), thumb's Kapandji scores, disabilies of the arm, shoulder, and hand (DASH) scores, grip and pinch strength and time to return to work were compared.Results:All cases were followed up for 19.6±6.3 months (range, 11-36 months). The postoperative X-ray showed all the CMCJs were reduced with a normal height of first metacarpal. The mean time for patients to return to their daily activities was 18.69±3.70 d and the mean time to return to work was 24.63±4.91 d. The average VAS score decreased from 6.56±1.15 preoperatively to 1.00 (0.75, 1.25). The preoperative Kapandji's score was 8.00±0.82 and the postoperative Kapandji's score was 8.00 (7.25, 9.00). The average DASH values improved from 24.06±3.19 to 4.00 (3.00, 5.00). The were significant differences except for Kapandji score ( Z=-4.905, P<0.001; Z=-0.121, P=0.905; Z=-4.846, P<0.001). The mean grip and pinch strength showed improvement from an average of 16.4 (14.13, 18.68) kg and 1.70±0.35 kg to 26.14±3.27 kg and 3.58±0.91 kg with significant difference ( Z=-4.617, P<0.001; t=-7.669, P<0.001). Conclusion:Arthroscopic partial trapeziectomy and suture button suspensionplasty is a minimally invasive surgery for the treatment of first CMCJ Eaton stage II/III arthrosis. By this technique, the patients' existing instability and pain problems can be solved.
4.Mechanism of Yes-Associated Protein 1 Ameliorating Aristolochic Acid 1-Induced Liver Injury in Mice Based on Untargeted Metabolomics Techniques
Yu XUE ; Caige LI ; Yiwei LIU ; Jiali YANG ; Zhiqin ZHANG ; Jingmin JI ; Kun YU ; Xinli SHI
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(1):46-55
Objective To investigate the mechanism of Yes-associated protein 1(YAP1)ameliorating aristolochic acid 1(AAI)-induced liver injury in mice based on untargeted metabolomics techniques.Methods There were 83-week-old male hepatocyte-specific Yap1 gene knockout mice(genotyped as Yap1Flox/Flox,Albumin-Cre,aka.Yap1LKO)were randomly selected as the Yap1LKO+AAI group,and 8 Yap1Flox control mice as the Yap1Flox+AAI group.Both groups were injected intraperitoneally with AAI at a dose of 2.5 mg·kg-1·d-1 for 14 consecutive days.Genotypes were identified by tail PCR;serum alanine transaminase(ALT)and aspartate transaminase(AST)activities were determined by microplate assay;histopathological changes of liver tissue were observed by HE staining;and the protein expression of YAP1 in liver tissue was determined by immunohistochemistry.The untargeted metabolomics approach was used to analyze the liver tissue differential metabolites,and the samples were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbit trap high-resolution mass spectrometry,and the differential metabolites were screened by principal component analysis(PCA),Partial least square-discriminant analysis(PLS-DA),and orthogonal partial least squares-discriminant analysis(OPLS-DA);using HMDB database and METLIN database to identify metabolites,and the pathway enrichment of differential metabolites was analyzed by KEGG database.Results(1)After 14 days of AAI induction,the increase of body mass in Yap1LKO mice was lower than that in Yap1Flox mice,but there was no statistical significance(P>0.05).On day 14,compared with the Yap1Flox+AAI group,the serum ALT and AST enzyme activities in the Yap1LKO+AAI group of mice were significantly increased(P<0.05),and the histopathological damage of the liver was significantly aggravated.The livers of the Yap1Flox mice had a positive protein expression of YAP1,whereas the Yap1LKO mice did not have a positive protein expression of YAP1.(2)A total of 139 differential metabolites with significant changes(VIP>1 and P<0.05)were screened by metabonomic analysis;compared with Yap1LKO+ AAI group,62 liver metabolites in Yap1Flox+AAI group were up-regulated,including choline,taurine,hypotaurine,α-linolenic acid,eleostearic acid,chenodeoxycholic acid and so on.Seventy-seven metabolites were down-regulated including glycerophosphocholine,L-phosphatidylcholine,L-glutamine,L-serine,L-glutathione,5-methionine,phenylalanine,glucose 6-phosphate,lactic acid,uric acid glycosides,etc..KEGG-enriched pathways were mainly choline metabolism,glycerophospholipid metabolism,insulin resistance,glutathione metabolism,etc..Conclusion Hepatocyte-specific Yap1 gene knockout exacerbated AAI-induced liver injury in mice,and YAP1 was involved in the regulation of choline metabolism and glycerophospholipid metabolism through the up-regulation of unsaturated fatty acids,such as choline and taurine,which ameliorated AAI-induced liver injury in mice.
5.Clinical analysis of patients with cardiopulmonary resuscitation in emergency department and establishment of prediction model of restoration of spontaneous circulation in hospital
Junfang LIU ; Xiaoxia DUAN ; Zhiqin MA ; Haoxue FU ; Bo WU ; Qi WANG
Chinese Critical Care Medicine 2024;36(1):40-43
Objective:To screen the independent influencing factors of restoration of spontaneous circulation (ROSC) in patients after cardiopulmonary resuscitation (CPR) and establish a predictive model, and explore its clinical value.Methods:A retrospective case control study was conducted. The clinical data of cardiac arrest patients admitted to the emergency department of Tangdu Hospital of Air Force Military Medical University and received CPR from January to July 2023 were analyzed, including general information, blood biochemical indicators, main cause of cardiac arrest, whether it was defibrillation rhythm, duration from admission to CPR, and whether ROSC was achieved. The clinical data between the patients whether achieved ROSC or not were compared. The binary multivariate Logistic regression analysis was used to screen the independent influencing factors of ROSC in in-hospital CPR patients. According to the above influencing factors, the ROSC prediction model was established, and the receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of the model for ROSC.Results:A total of 235 patients who received CPR in the emergency department were enrolled, including 153 cases (65.11%) of in-hospital CPR and 82 cases (34.89%) of out-of-hospital CPR. The ROSC ratio was 30.21% (71/235). Among all patients, the majority were aged 61-80 years [40.43% (95/235)], and cardiogenic disease was the main cause of cardiac arrest [32.77% (77/235)]. Among 153 patients with in-hospital CPR, 89 were non-ROSC and 64 were ROSC with ROSC rate of 41.83%. Compared with the non-ROSC group, the patients in the ROSC group had lower blood lactic acid (Lac), N-terminal pro-brain natriuretic peptide (NT-proBNP), Lac/albumin (Alb) ratio (LAR), and ratio of non-defibrillation rhythm [Lac (mmol/L): 5.50 (2.33, 9.65) vs. 7.10 (3.50, 13.35), NT-proBNP (μg/L): 0.87 (0.20, 8.68) vs. 3.00 (0.58, 20.17), LAR: 0.14 (0.07, 0.29) vs. 0.19 (0.10, 0.43), non-defibrillation rhythm ratio: 68.75% (44/64) vs. 93.26% (83/89)], higher actual base excess (ABE) and Alb [ABE (mmol/L): -3.95 (-12.75, 0.23) vs. -7.50 (-13.50, -3.35), Alb (g/L): 38.13±7.03 vs. 34.09±7.81], and shorter duration from admission to CPR [hours: 3.25 (1.00, 14.00) vs. 8.00 (2.00, 27.50)], the differences were statistically significant (all P < 0.05). Binary multivariate Logistic regression analysis showed that LAR [odds ratio ( OR) = 0.037, 95% confidence interval (95% CI) was 0.005-0.287], non-defibrillation rhythm ( OR = 0.145, 95% CI was 0.049-0.426), and duration from admission to CPR ( OR = 0.984, 95% CI was 0.972-0.997) were independent influencing factors for ROSC in hospitalized CPR patients (all P < 0.05). Based on the above influencing factors, a ROSC prediction model was constructed through regression analysis results. The ROC curve analysis showed that the area under the ROC curve (AUC) for predicting ROSC in in-hospital CPR patients was 0.757 (95% CI was 0.680-0.834), Yoden index was 0.429, sensitivity was 76.6%, and specificity was 66.3%. Conclusions:LAR, non-defibrillation rhythm and duration from admission to CPR were independent influencing factors for ROSC in patients with in-hospital CPR. The ROSC prediction model established based on the above influencing factors has a good predictive value for ROSC of CPR patients in hospital, and can guide clinicians to evaluate the prognosis of patients through relevant indicators as early as possible.
6.Early warning value and model construction of laboratory indexes of patients with hemorrhagic fever with renal syndrome to severe patients
Xiaoxia DUAN ; Junfang LIU ; Qinqin YANG ; Jie LIU ; Bo WU ; Zhiqin MA ; Haoxue FU ; Qi WANG
Chinese Journal of Emergency Medicine 2024;33(7):1006-1010
Objective:To analyze the early warning value of laboratory examination on admission of patients with hemorrhagic fever with renal syndrome to critically ill patients.Meetods:In this study, a retrospective case-control study was used to analyze the clinical data and laboratory examination results of patients with hemorrhagic fever with renal syndrome admitted to the emergency department of Tangdu Hospital of Air Force Medical University from January 2021 to January 2022. According to the patient's laboratory indexes and clinical symptoms, the patients were divided into mild, moderate, severe and critical groups. The general data of the two groups were compared, and the independent risk factors of critically ill patients were screened by multi-factor logistic regression analysis, the predictive model of severe HFRS patients was constructed, and the ROC curve was drawn. .Results:Of the 164 patients with HFRS, 50 were in the severe group and 114 in the mild group. The serum levels of WBC, AST, ALT, Cr, BUN, DD and PCT in the severe group were higher than those in the mild group, while the levels of PLT, ALB and PTA in the severe group were lower than those in the mild group. Multiple logistic regression analysis showed that WBC, PLT and PCT were independent influencing factors for the progression of critically ill patients. The predictive model of severe HFRS was established as follows: logit (P) = -0.321 + 0.040 WBC (×10 9/L) -0.045 PLT (×10 9/L) + 0.086 PCT(ng/mL). The early warning ef?cacy of WBC, PLT, And PCT for severe HFRS was further analyzed. The area under the ROC curve (area under curve, AUC) was 0.779, 0.842, 0.862, and the optimal threshold was 10.435×109/L, 41.5 ×109/Land 2.97 ng/mL, respectively. The AUC of joint detection is 0.900, the sensitivity is 88.0%, and the speci?city is 82.5%, which is better than that of a single laboratory. . Conclusions:HFRS laboratory indexes have certain clinical signi?cance for the identi?cation of critically ill patients, in which serum WBC, PLT and PCT indexes are the risk factors of severe HFRS, which provides a theoretical basis for clinical diagnosis, treatment and prognosis of severe HFRS patients.
7.Amide proton transfer weighted imaging in assessment of acid-base metabolism in chronic ischemic brain tissue
Hongxia LI ; Chao XIA ; Jiaxin ZENG ; Zhiqin LIU ; Xia WEI ; Yuan SUN ; Xing LI ; Ziyu LI ; Yue LI ; Anqi XIAO ; Yi LIU ; Kai AI ; Su LYU ; Na HU
Chinese Journal of Radiology 2024;58(8):807-812
Objective:To explore changes of acid-base metabolism in the brain tissue of patients with chronic ischemic cerebrovascular disease (CICVD) using MRI amide proton transfer-weighted (APTw) imaging.Methods:This was a cross-sectional study. From January 2021 to July 2022, thirty-nine patients with CICVD at West China Hospital, Sichuan University were retrospectively included. All patients received CT perfusion (CTP) and APTw imaging. NeuBrainCARE brain perfusion software was used to analyze the impaired perfusion sites and measure the mean transit time (MTT) and time to peak (TTP). Standard spatial matching between CTP and APTw images was performed to measure the APTw values of the same sites. For comparison with normal tissue, APTw values were measured for normal-appearing white matter (NAWM) in the ipsilateral cerebral hemisphere, the contralateral cerebral hemisphere, and the ipsilateral cerebellar hemisphere in areas of impaired perfusion. ANOVA was used to compare the APTw values of impaired perfusion brain tissue, ipsilateral cerebral NAWM, contralateral cerebral NAWM, and ipsilateral cerebellar NAWM. The Bonferroni method was used to correct for multiple comparisons. Pearson correlation coefficient was used to analyze the correlation between APTw values and MTT and TTP in the cerebral tissue with impaired perfusion.Results:In 39 patients with CICVD, both the mean and minimum APTw values of cerebral tissue with impaired perfusion were significantly lower than those in the NAWM of the ipsilateral cerebral hemisphere, the contralateral cerebral hemisphere, and the ipsilateral cerebellar hemisphere ( P<0.001). In the NAWM of the cerebellar hemispheres with unimpaired perfusion, both the mean and minimum APTw values were significantly higher than those in the ipsilateral cerebral hemispheres and the contralateral cerebral hemisphere ( P<0.001). Correlation analysis showed that MTT was significantly negatively correlated with both the mean APTw and the minimum APTw ( r values were -0.90 and -0.82, P<0.001). TTP was significantly negatively correlated with both the mean APTw and the minimum APTw ( r values were -0.86 and -0.78, P<0.001). Conclusion:APTw value can reflect acidosis in cerebral tissue with impaired perfusion in patients with CICVD.
8.Dihydroartemisinin increased the abundance of Akkermansia muciniphila by YAP1 depression that sensitizes hepatocellular carcinoma to anti-PD-1 immunotherapy.
Zhiqin ZHANG ; Xinli SHI ; Jingmin JI ; Yinglin GUO ; Qing PENG ; Liyuan HAO ; Yu XUE ; Yiwei LIU ; Caige LI ; Junlan LU ; Kun YU
Frontiers of Medicine 2023;17(4):729-746
The effect of anti-programmed cell death 1 (anti-PD-1) immunotherapy is limited in patients with hepatocellular carcinoma (HCC). Yes-associated protein 1 (YAP1) expression increased in liver tumor cells in early HCC, and Akkermansia muciniphila abundance decreased in the colon. The response to anti-PD-1 treatment is associated with A. muciniphila abundance in many tumors. However, the interaction between A. muciniphila abundance and YAP1 expression remains unclear in HCC. Here, anti-PD-1 treatment decreased A. muciniphila abundance in the colon, but increased YAP1 expression in the tumor cells by mice with liver tumors in situ. Mechanistically, hepatocyte-specific Yap1 knockout (Yap1LKO) maintained bile acid homeostasis in the liver, resulting in an increased abundance of A. muciniphila in the colon. Yap1 knockout enhanced anti-PD-1 efficacy. Therefore, YAP1 inhibition is a potential target for increasing A. muciniphila abundance to promote anti-PD-1 efficacy in liver tumors. Dihydroartemisinin (DHA), acting as YAP1 inhibitor, increased A. muciniphila abundance to sensitize anti-PD-1 therapy. A. muciniphila by gavage increased the number and activation of CD8+ T cells in liver tumor niches during DHA treatment or combination with anti-PD-1. Our findings suggested that the combination anti-PD-1 with DHA is an effective strategy for liver tumor treatment.
9.Research progress of evaluation tools for sexual health care of nurses in oncology department
Jing XU ; Wenjin ZHANG ; Wenli LIU ; Zhiqin CAO ; Xingfeng CHEN ; Yao FU
Chinese Journal of Practical Nursing 2023;39(25):1996-2001
This paper introduces the concepts related to sexual health and sexual health care, summarizes the contents, application scope and limitations of sexual health care assessment tools for oncology nurses at home and abroad, analyzes the problems existing in the assessment tools and puts forward suggestions, aiming at providing theoretical reference for the localization development of sexual health care assessment tools and the development of sexual health care.
10.Research progress on symptom burden of colorectal cancer survivors
Hui LIU ; Caiyan DING ; Xiao ZHOU ; Zhiqin SUN
Chinese Journal of Modern Nursing 2023;29(2):276-280
Due to the lack of understanding of the concept of staging of survivors, clinical nurses pay different attention to the symptom burden of colorectal cancer survivors in different stages, resulting in different levels of symptom burden, compliance, and quality of life. This article starts from the definition and stages of survivors, introduces the current situation of the symptom burden of colorectal cancer survivors under different stages, analyzes and compares the main evaluation tools, and combs the influencing factors of the symptom burden of colorectal cancer survivors from various aspects. On this basis, this article puts forward the shortcomings and enlightenment of existing research, aiming to help doctors and nurses understand the staging of survivors, accurately grasp the level of symptom burden of colorectal cancer survivors, and provide reference for further clinical research.

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