1.A-485 alleviates tubular lipid accumulation by inhibiting H3K18ac/H3K27ac induced by P300/CBP in diabetic mice
Li MENG ; Yan ZHU ; Yan YANG ; Ting WU ; Yunzhuo REN ; Linshan DU ; Shijie ZENG ; Chunyang DU
Chinese Journal of Clinical and Experimental Pathology 2024;40(5):509-514
Purpose To investigate the protective effect and mechanism of A-485 on renal tubular injury in diabetic mice.Methods Eighteen male C57BL/6J mice were randomly divided into three groups:Control group,diabetic kidney dis-ease(DKD)group and A-485 treatment group.The DKD mice model was established by feeding high-fat diet for 8 weeks and intraperitoneal injection of streptozotocin for 5 days.Subsequent-ly,the A-485 treatment group was given A-485(10 mg/kg/day)by intraperitoneal injection every other day for 4 weeks.After treatment,the renal function,P300 enzyme activity and lipid deposition in renal tissue were measured.Western blot a-nalysis was performed to detect SREBP-1,FASN,ACC,ChREBP,P300,CBP,H3K18ac and H3K27ac protein levels.Results Compared with control mice,the levels of FBG,BUN,Scr and UAE were significantly increased in diabetic mice(FBG:2.52 times,BUN:2.89 times,Scr:2.13 times,UAE:4.21 times),while diabetic mice treatment with A-485 exhibi-ted a remarkable decrease on BUN,Scr and UAE(BUN:0.511 times,Scr:0.636 times,UAE:0.574 times,P<0.01).The results of the transmission electron microscopy and oil red O stai-ning showed that A-485 treatment prevents lipid droplets forma-tion and up-regulation of SREBP-1,FASN,ACC and ChREBP in renal tubular cells of diabetic mice(SREBP-1:0.544 times,FASN:0.449 times,ACC:0.306 times,ChREBP:0.317 times,P<0.01).Furthermore,A-485 intervention downregu-lated the enzyme activity of P300(0.546 times)and suppressed the expression of H3K18ac(0.337 times)and H3K27ac(0.308 times,P<0.01).Conclusion A-485 can significant-ly improve renal lipid metabolic disorder in diabetic mice,which may be achieved by inhibiting p300-induced H3K18ac and H3K27ac.
2.Biomechanical Environment Regulates Biomimetic Mineralization of Bone Matrix
Chunyang MA ; Tianming DU ; Xufeng NIU ; Yubo FAN
Journal of Medical Biomechanics 2022;37(2):E200-E210
Bone defects have always been an important cause of threat to human health, and artificial biomimetic bone repair replacement materials are currently one of the most effective and feasible solution approaches to treat bone damage. To develop artificial bone biomimetic materials, an in vitro biomimetic mineralization system must be constructed first to study in vitro biomimetic mineralization mechanism of natural bone matrix. Collagen is a template for mineralization, and its properties such as crosslinking degree, diameter, osmotic pressure, and surface charge can all directly affect mineralization progress. The biochemical and mechanical environments in which mineralization occurs are also quite distinct in their effects on mineralization process, particularly noncollagenous proteins and fluid shear stress (FSS). FSS is considered to be the main mechanical stimulation of bone tissues in micro-environment, which is of great significance to bone growth, repair and health maintenance. FSS at different levels and loading regimes has significant effects on transformation of amorphous calcium phosphate to bone apatite, self-assembly and directional alignment of collagen fibrils, and formation of hierarchical intrafibrillar mineralization. In this paper, the factors affecting collagen mineralization and their mechanism were summarized, with focus on regulation of FSS on collagen mineralization, and development direction in future was also prospected.
3.Corneal morphology and visual quality observation after Trans-PRK with smart pulse technology in the correction of myopia and astigmatism
Yuqin DU ; Chunyang ZHOU ; Yuehua ZHOU ; Yu LI ; Dan SU
Chinese Journal of Experimental Ophthalmology 2022;40(11):1078-1084
Objective:To observe the corneal morphology and visual quality after transepithelial photorefractive keratectomy (Trans-PRK) with smart pulse technique (SPT) and 1 050 Hz cutting frequency in the correction of myopia and astigmatism.Methods:A self-controlled case series study was conducted.Sixty five eyes of 33 patients who underwent Trans-PRK surgery in Ineye Hospital of Chengdu University of TCM from July 2017 to June 2018 were followed up for 6 months.The uncorrected visual acuity (UCVA) converted to logarithm of the minimum angle of resolution (LogMAR) unit, best corrected visual acuity (BCVA) (LogMAR), and spherical equivalent (SE) of the subjects were recorded.The anterior corneal surface symmetry index (SI), the anterior corneal surface Q value in the range of 6, 7, 8, and 9 mm diameter, the spherical aberration, coma, trefoil and total higher-order aberration of the anterior corneal surface, the strehl ratio (SR), and the modulation transfer function (MTF) of 10, 20, 30, and 40 c/d in the horizontal and vertical meridian directions before and after surgery were measured with Sirius corneal topography analyzer.The differences of each index among different time points were compared, and the correlation between indexes was analyzed by Pearson correlation analysis.This study followed the Declaration of Helsinki.The study protocol was approved by the Medical Ethics Committee of Ineye Hospital of Chengdu University of TCM (No.2020yh-004). All patients signed the informed consent form before surgery.Results:The average preoperative BCVA and SE were -0.09±0.06 and (-4.24±1.24)D.The mean UCVA and SE at 7 days, 1, 3 and 6 months postoperatively were -0.10±0.08 and (0.03±0.63)D, -0.12±0.06 and (0.08±0.53)D, 1.16±0.06 and (0.02±0.79)D, -0.18±0.05 and (0.08±0.37)D, respectively.The SI at different time points after the surgery were significantly higher than that before operation (all at P<0.05). At 1, 3 and 6 months after surgery, the Q value of anterior corneal surface in different diameter ranges increased from negative to positive, showing statistically significant differences (all at P<0.05). At each time point after surgery, the trefoil and total higher-order aberrations of the anterior corneal surface increased to varying degrees.Coma at 7 days and 6 months after surgery were significantly higher than that before surgery, and spherical aberration at 3 and 6 months after surgery were significantly higher than that before surgery (all at P<0.05). The SR values at 3 and 6 months after operation were significantly higher than that before operation (all at P<0.05). At 6 months after operation, the MTF values at different spatial frequencies of the horizontal meridian and the MTF values at 30 and 40c/d spatial frequencies of the vertical meridian were lower than those before operation, and the differences were statistically significant (all at P<0.05). The correlation analysis showed that the Q value of different diameter ranges was positively correlated with spherical aberration ( r=0.798-0.925, P<0.05), total higher-order aberration ( r=0.596-0.630, P<0.05), SI ( r=0.235-0.303, P<0.05) and corneal ablation depth ( r=0.583-0.659, P<0.05) at 6 months after surgery.SI was positively correlated with spherical aberration ( r=0.307, P<0.05), coma ( r=0.424, P<0.05), total higher-order aberration ( r=0.300, P<0.05), corneal ablation depth ( r=0.227, P<0.05), and eccentric cutting amount ( r=0.281, P<0.05). There was no correlation between SR and aberration, corneal ablation depth, eccentric cutting amount, etc.(all at P≥0.05). Conclusions:Trans-PRK using SPT to correct myopic astigmatism can improve vision, stabilize diopter, enhance retinal imaging quality, increase the asymmetry of the anterior corneal surface, and introduce different degrees of higher-order aberrations.
4.Effect of Potassium Solubilizing Bacteria on Rhizosphere Soil Microenvironment of Paris polyphylla var. yunnanensis
Shunxin ZHAO ; Chunyang JIANG ; Qiaosheng DENG ; Lingfeng XU ; Huihui DU ; Nong ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(16):172-179
ObjectiveTo investigate the effects of the inoculation of potassium-solubilizing bacteria on the rhizosphere soil microenvironment of Paris polyphylla var. yunnanensis. MethodThe effects of different potassium-solubilizing bacteria on the physical and chemical properties, microbial community structure, and soil enzyme activity in the rhizosphere soil of P. polyphylla var. yunnanensis were investigated by pot planting at room temperature. The correlation of various indexes was analyzed. ResultThe inoculation with different potassium-solubilizing bacteria could significantly affect the physical and chemical properties of rhizosphere soil of P. polyphylla var. yunnanensis. The mass fractions of available nitrogen, available phosphorus, and available potassium were 24.5-90.5 mg·kg-1, 2.53-25.9 mg·kg-1, and 132-312 mg·kg-1, respectively, and the soil pH was 7.08-7.75, which were in line with the optimal ranges of P. polyphylla var. yunnanensis planting. The inoculation of different potassium-solubilizing bacteria could affect the number of bacteria, actinomycetes, and fungi in rhizosphere soil to varying degrees. The transformation of soil from "fungal type" to "bacterial type" marks the improvement of soil fertility. It also affected the enzyme activity of rhizosphere soil, and the activities of neutral phosphatase, protease, and polyphenol oxidase showed an increasing trend. The correlation analysis showed that the number of bacteria was negatively correlated with the number of fungi (r=-0.856, P<0.01), positively correlated with the number of actinomycetes, the content of available nitrogen and available potassium, and negatively correlated with soil pH. ConclusionThe inoculation of potassium-solubilizing bacteria can effectively improve the content of available potassium, available nitrogen, available phosphorus, and other nutrients in the rhizosphere soil of P. polyphylla var. yunnanensis, improve soil fertility, alleviate the continuous cropping obstacles of P. polyphylla var. yunnanensis, and lay a theoretical foundation for the green and sustainable development of P. polyphylla var. yunnanensis.
5.Metabolomic alterations of human lung bronchial epithelial cells infected with human rhinovirus 1B
Meng SU ; Dan LI ; Pingping SUN ; Chunyang WANG ; Jiangli WANG ; Hong WANG ; Qing ZHANG ; Luanying DU ; Guangcheng XIE
Chinese Journal of Microbiology and Immunology 2021;41(7):545-549
Objective:To research the metabolomic alterations of human lung bronchial epithelial cells infected with human rhinovirus 1B (HRV1B).Methods:Untargeted metabolomics was used to determine the metabolomic alterations in human lung bronchial epithelial cells (BEAS-2B) 6 h, 12 h and during the dynamic process (6 h∶12 h) after HRV1B infection.Results:A total of 93 differentially significant metabolites (DSMs) (47 DSMs were up-regulated and 46 DSMs were down-regulated) and 88 DSMs (37 DSMs were up-regulated and 51 DSMs were down-regulated) at post infection of HRV1B in BEAS-2B at 6 h or 12 h, respectively. A total of 30 DSMs (12 DSMs were up-regulated and 18 DSMs were down-regulated) in a dynamic process (6 h∶12 h) after HRV1B infection. Unknown metabolites took up most proportions. The trends of fatty acid, lipid, amino acid, nucleotide and carbohydrate were increased along with the prolonging of HRV1B infection. DSMs such as Diisononyl phthalate was co-detected DSMs among three groups.Conclusions:Metabolites such as fatty acid, lipid, amino acid, nucleotide and carbohydrate of BEAS-2B cells are changed induced by HRV1B infection.
6.Comparison of clinical effects between TransPRK with intelligent pulse technology and SMILE for myopia
Yuqin DU ; Chunyang ZHOU ; Yuehua ZHOU ; Yu LI ; Dan SU ; Long WEN
Chinese Journal of Experimental Ophthalmology 2020;38(6):489-493
Objective:To compare the clinical outcome of transepithelial photorefractive keratectomy (TransPRK) using 1 050 Hz ablation frequency and intelligent pulse technique (SPT) and small incision lenticule extraction (SMILE) for myopia and astigmatism.Methods:A cohort study was performed.Eighty-five eyes of 43 patients who received TransPRK for myopia and 85 eyes of 46 patients who received SMILE for myopia in the Ineye Hospital of Chengdu University of TCM were enrolled from August 2017 to April 2018.The follow-up duration was 6 months.The changes of visual acuity and diopter were observed and compared before and after operation, and the predictability, stability, safety, effectiveness and long-term vision were compared between the different surgeries.This study complied with the Declaration of Helsinki and the study protocol was approved by the Ethics Committee of Ineye Hospital of Chengdu University of TCM.Results:The refractive power tended to be emmetropic and relatively stable in the TransPRK group, and the refraction varied from mild hyperopia to emmetropic gradually during 6 months after SMILE.There was no significant difference in the spherical equivalent (SE) between the two groups before and after operation (all at P>0.05). No significant difference was found in mean validity index between the two groups at 6 months after surgery (1.189±0.248 vs.1.120±0.205; t=1.862, P=0.065). The uncorrected visual acuity (UCVA) in the SMILE group was significantly higher than that in the TransPRK group at 7 days and 1 month after surgery ( P<0.05), and there was no significant difference in UCVA between the two groups at 3 months and 6 months after surgery ( P>0.05). The safety index at 6 months after surgery in the TransPRK group was 1.209±0.222, which was significantly higher than 1.143±0.178 in the SMILE group, with a significant difference between the two groups ( t=2.024, P=0.045). Conclusions:The predictability, stability, safety, effectiveness and long-term vision are good after TransPRK with SPT and SMILE for myopia and astigmatism.The safety index is better in TransPRK compared with SMILE, and the restoration of vision is faster after SMILE than that after TransPRK.
7.Analysis of the effects of immunity index and blood inflammatory markers pre- and post-radiotherapy on prognosis of clinical stage Ⅲ esophageal cancer patients
Chunyang SONG ; Shuchai ZHU ; Wenbin SHEN ; Sina GAO ; Xingyu DU ; Yan ZHAO ; Jinrui XU
Chinese Journal of Radiological Medicine and Protection 2020;40(3):189-195
Objective:To study the effects of immunity index and blood inflammatory markers pre- and post-radiotherapy on prognosis of esophageal cancer patients with clinical stage Ⅲ.Methods:A total of 84 esophageal cancer patients with clinical stage Ⅲ (T 4N 1M 0) in Fourth Hospital of Hebei Medical University were analyzed, from May 2010 to April 2012. Intensity-modulated radiotherapy was delivered with a dose of 56-66 Gy/1.8-2.0 Gy per fraction. Flow cytometry was used to analyze the distribution of T-lymphocyte subsets (CD3, CD4, CD8, CD4/CD8) and natural killer cells (CD56) in the peripheral blood pre- and post- radiotherapy. Neutrophil-lymphocyte ratio (NLR) pre- and post- radiotherapy were also tested. The correlation of immunity index and blood inflammatory markers with prognosis was analyzed by univariate and multivariate analysis. Results:For all patients, the 1-, 3- and 5-year overall survival (OS) rates were 78.57%, 34.52% and 19.59%, respectively. The median OS time was 22.60 months. The 1-, 3- and 5-year progression free survival (PFS) rates were 69.05%, 27.38% and 12.09%, respectively. The median PFS time was 21.20 months. The objective response rate was 61.90%, with 11 patients of complete remission (CR) and 41 patients of partial remission (PR). Univariate analysis revealed that NLR before radiotherapy, T-lymphocyte subsets (CD3, CD4 and CD4/CD8) after radiotherapy were significantly associated with OS and PFS (OS: χ 2=7.851, 4.443, 8.381, 5.972, P<0.05, PFS: χ 2= 7.475, 6.290, 9.659, 8.738, P<0.05). Multivariate COX regression analysis showed that NLR before radiotherapy, T-lymphocyte subsets (CD4, CD4/CD8) after radiotherapy were independent prognostic factors for OS (χ 2=10.464, 4.292, 5.507, P<0.05). The NLR before radiotherapy and CD4/CD8 after radiotherapy were independent prognostic factors for PFS (χ 2=10.835, 8.545, P<0.05). Conclusions:Radiotherapy may influence the immune function. NLR before radiotherapy and CD4/CD8 after radiotherapy are of great value in predicting the prognosis of esophageal cancer patients.
8.lncRNA HCG18 regulates the proliferation and metastasis of non-small cell lung cancer cells through targeting miR-17-5p/HMGA2 axis
QU Baoliang ; MU Huaibo ; GOU Jianqiang ; YANG Yu ; MA Shenghui ; DU Chunyang
Chinese Journal of Cancer Biotherapy 2019;26(4):409-416
Objective: To investigate the mechanism of lncRNA HCG18/miR-17-5p/HMGA2 axis regulating the proliferation and metastasis of non-small cell lung cancer (NSCLC) cells. Methods: Sixty-two pairs of NSCLC tissues and corresponding para-cancerous tissues collected at Central Hospital of Chengde City from June 2017 to June 2018 were used for this study; in addition, NSCLC cell lines (A549, NCI-H1299, H1650, NCI-H460) and human lung epithelial BEAS-B cells were also collected. mRNA expression levels of HCG18, miR-17-5p and high-mobility group AT-hook 2 (HMGA2) in NSCLC tissues and cell lines were measured by quantitative Real-time polymerase chain reaction (qPCR). Si-HCG18, miR-17-5p, miR-17-5p+HCG18 or pcDNA3.1-HMGA2 were transfected into A549 cells and NCI-H460 cells; CCK-8 assay was used to detect the proliferation of transfected cells, Transwell assay was used to detect the migration and invasion ability of cells, and Wb was used to analyze the expressions of HMGA2 and EMT associated proteins (E-cadherin, N-cadherin and vimentin). The target relationships between HCG18 and miR-17-5p, or between miR-17-5p and HMGA2 were confirmed by dual luciferase reporter gene assay. Mice A549 cell xenograft model with HCG18 knockdown was constructed, and the growth of transplanted tumor was observed. Results: lncRNA HCG18 was highly expressed in NSCLC tissues and cells (all P<0.01); HCG18 level was significantly increased in patients at late stage or with lymphnode metastasis; and high HCG18 level was correlated with poor prognosis and low survival rates of NSCLC patients (all P<0.01). Knockdown of HCG18 significantly inhibited NSCLC cell proliferation, migration and invasion (all P<0.01), up-regulated E-cadherin expression but suppressed N-cadherin and vimentin expression (all P<0.01), and the volume of xenograft was obviously decreased (P<0.05). Dual luciferase reporter gene assay confirmed the relationship between HCG18 and miR-17-5p as well as miR-17-5p and HMGA2. miR-17-5p transfection significantly inhibited NSCLC cell proliferation, migration and invasion (all P<0.01), and up-regulated E-cadherin expression, reversely suppressed N-cadherin and vimentin expression (all P<0.01); however, miR-17-5p + HCG18 transfection reversed the effect of miR-17-5p on NSCLCcells.Conclusion:HCG18promotes the proliferationandmigrationofNSCLCcellsthrough regulating miR-17-5p/HMGA2 axis.
9.Value of vacuum sealing drainage combined with external fixator in patients with severe damage of lower extremities by limb salvage
Journal of Clinical Medicine in Practice 2018;22(11):83-86
Objective To investigate the value of vacuum sealing drainage (VSD) combined with external fixator in patients with severe damage of lower extremities by limb salvage.Methods Totally 100 patients with severe damage of lower extremities were treated with limb salvage,and they were divided into observation group and control group.Dressing replacement combined with external fixator was used in control group,while the observation group was treated with VSD combined with external fixation.The recovery and complications were observed and analyzed.Results The average operation times,bacterial negative-conversing time,wound healing time and fracture healing time in observation group were significantly better than those in control group (P < 0.05).The incidence rate of osteomyelitis,deep infection,complications and amputation in observation group were significantly lower than the control group (P < 0.05).Conclusion VSD combined with external fixation can effectively maintain fracture stability and promote wound healing in patients with severe damage of lower extremities by limb salvage.
10.Intraoperative cerebral perfusion monitoring by evoked potential and transcranial doppler ultrasonography in carotid endarterectomy: a comparative study
Sen YU ; Chunyang LIANG ; Shaopeng DU ; Hairuo GUO ; Shang MA ; Zijun HE ; Chunsen SHEN ; Yang YANG ; Ruxiang XU
Chinese Journal of Neuromedicine 2018;17(4):381-386
Objective To investigate the effectiveness of evoked potential in monitoring cerebral perfusion during carotid endarterectomy by a retrospective cohort study.Methods A retrospective cohort survey of clinical data of 59 patients,who underwent carotid endarterectomy in our hospital from September 2013 to December 2016,was performed.All patients were monitored by transcranial doppler ultrasonography (TCD) and somatosensory evoked potential (SEP),motor evoked potential (MEP) for changes of cerebral blood flow;the monitoring of TCD was defaulted as "gold standard",recording monitoring results at different time points.By drawing the four table,the sensitivity,specificity,positive predictive value,negative predictive value of SEP and MEP during cerebral hypoperfusion were calculated,and correlation analyses between SEP and TCD,and between MEP and TCD were performed.Through receiver operating characteristic (ROC) curve,SEP monitoring threshold of cerebral hypoperfusion was predicted.Results The sensitivity,specificity,positive predictive value,and negative predictive value of SEP in predicting intra-operative cerebral hypoperfusion were 60.00%,91.84%,60.00%,and 91.84% when SEP amplitude declined beyond 50%;the sensitivity,specificity,positive predictive value and negative predictive value of SEP in predicting intra-operative cerebral hypoperfusion were 70.00%,93.88%,70.00% and 93.88% when SEP latency extended beyond 10%.The sensitivity,specificity,positive predictive value,and negative predictive value of MEP in predicting intra-operative cerebral hypoperfusion were 30.00%,97.96%,75.00%,and 87.27% when MEP amplitude declined beyond 50%.Decline of SEP and MEP amplitudes and extension of SEP latency have positive correlations with TCD.ROC indicated that the amplitude of somatosensory evoked potentials could predict intraoperative hypoperfusion when it decreased by 51.0% than the baseline monitoring value after carotid artery occlusion,with sensitivity of 100.0%,specificity of 89.8% and area under the curve of 0.918 (95%CI:0.846~0.990,P=0.024).ROC also showed that the latent phase of somatosensory evoked potentials could predict intraoperative hypoperfusion when it was prolonged >9.8% compared to the baseline monitoring value after carotid artery occlusion,with sensitivity of 100.0%,specificity of 92.9%and area under the curve of 0.941 (95%CI 0.878~0.995,P=0.014).Conclusion Evoked potentials can real-time monitor intra-operative cerebral hypoperfusion continuously in carotid endarterectomy,enjoying high sensitivity and specificity;in addition,decline of SEP amplitude and extension of SEP latency have higher sensitivity than MEP.

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