1.Sulodexide inhibits neointimal hyperplasia of arteriovenous fistulas in rats through inactivation of YAP
Yaxin LI ; Bingyu LI ; Xin LIN ; Xuan LIU ; Chenglin DAI ; Yu ZHAO ; Qining FU ; Yun WANG
Journal of Army Medical University 2024;46(12):1403-1409
Objective To explore the role of sulodexide(SDX)in neointimal hyperplasia of arteriovenous fistulas(AVFs)in chronic kidney disease(CKD)rats and its possible mechanism.Methods A total of 18 male rats(weighing 300±50 g)were randomly and equally divided into AVF group,CKD+AVF group(CKD induction followed by AVF surgery and then gavaged with normal saline for 2 months),and CKD+AVF+SDX group[treated as in the CKD+AVF group but with 8 mg/(kg·d)SDX gavage].HE staining was used to observe the degree of neointimal hyperplasia.The expression of Hippo pathway related molecules,Yes-associated protein(YAP),pYAP and connective tissue growth factor(CTGF,YAP downstream target protein,one of mesenchymal marker)was detected by immunofluorescence assay.After human umbilical vein cell fusion EAHy926 cells were treated with 0,2.5,5,10,20 or 40 μg/mL SDX for 24 h,and with 2.5 μg/mL SDXfor24,48 or 72 h,respectively,CCK-8 assay was used to measure cell survival rate.Moreover,the serum sample from CKD rat was used to treat EAHy926 cells,and then the cells were treated with SDX or YAP inhibitor verteporfin.The expression levels of YAP,pYAP,CTGF and endothelial cell marker CD31 were detected by Western blotting.Results HE staining and immunofluorescence assay showed that CKD rats had serious neointimal hyperplasia in AVFs(P<0.05),and slightly lower expression of pYAP and enhanced expression of CTGF(P<0.05)when compared with the rats of the AVF group.While,SDX treatment alleviated the neointimal hyperplasia of AVFs,enhanced the expression of pYAP and reduced the expression of CTGF(P<0.05).CCK-8 assay showed that cell survival rate was decreased significantly in a dose-and time-dependent manner after SDX treatment(P<0.05).Western blotting revealed that SDX increased the expression of pYAP and CD31 while inhibited the expression of CTGF in EAHy926 cells(P<0.05),which was consistent with the effect of verteporfin treatment.Conclusion SDX can block YAP activation caused by CKD and attenuate neointimal hyperplasia in AVFs.
2.Renal abscess induced by fish bone ingestion: a case report
Yucheng GE ; Zhenqiang ZHAO ; Ruichao ZHAN ; Yukun LIU ; Chenglin ZHAO ; Tingting ZHANG ; Ye TIAN ; Wenying WANG
Chinese Journal of Urology 2023;44(9):704-705
Renal abscess caused by fish bone ingestion is extremely rare and has not been reported in the literature. A male patient presented with a 1-week history of flank pain and a 2-day history of fever. Urinary ultrasound and CT scan showed an irregular hypodense lesion in the left kidney and blurred thickening of the descending colon wall. Three-dimensional CT reconstruction images revealed a needle-like foreign body, which perforated from the descending colonic lumen to the left kidney. The patient had accidentally eaten fish bone one week prior. On the basis of clinical data, the diagnosis of renal abscess caused by foreign body was suspected. Accordingly, laparotomy was performed, the abscess was drained, and the colon was repaired. The foreign body was confirmed to be fish bone. The postoperative condition of the patient was uneventful, and the patient remained well in the 3 months' follow-up without any further complaints.
3.Design, synthesis, and biological evaluation of novel tetrahydroprotoberberine derivatives (THPBs) as proprotein convertase subtilisin/kexin type 9 (PCSK9) modulators for the treatment of hyperlipidemia.
Chenglin WU ; Cong XI ; Junhua TONG ; Jing ZHAO ; Hualiang JIANG ; Jiang WANG ; Yiping WANG ; Hong LIU
Acta Pharmaceutica Sinica B 2019;9(6):1216-1230
Proprotein convertase subtilisin/kexin type 9 (PCSK9) modulators may attenuate PCSK9-induced low-density lipoprotein receptor (LDLR) degradation in lysosome and promote the clearance of circulating low-density lipoprotein cholesterol (LDL-C). A novel series of tetrahydroprotoberberine derivatives (THPBs) were designed, synthesized, and evaluated as PCSK9 modulators for the treatment of hyperlipidemia. Among them, eight compounds exhibited excellent activities in downregulating hepatic PCSK9 expression better than berberine in HepG2 cells. In addition, five compounds , , , ()-, and ()- showed better performance in the low-density lipoprotein, labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI-LDL) uptake assay, compared with berberine at the same concentration. Compound , selected for evaluation, demonstrated significant reductions of total cholesterol (TC) and LDL-C in hyperlipidemic hamsters with a good pharmacokinetic profile. Further exploring of the lipid-lowering mechanism showed that compound promoted hepatic LDLR expression in a dose-dependent manner in HepG2 cells. Additional results of human related gene (hERG) inhibition assay indicated the potential druggability for compound , which is a promising lead compound for the development of PCSK9 modulator for the treatment of hyperlipidemia.
4.Experimental Research Progress on Acupuncture in Skeletal Muscle Atrophy (review)
Meng WU ; Chenglin TANG ; Siqin HUANG ; Dandan ZHAO ; Ao LUO ; Anning ZHANG ; Chengfang TAN ; Huiyu AN ; Li QIU
Chinese Journal of Rehabilitation Theory and Practice 2018;24(11):1292-1295
Irrespective of physiological or pathological skeletal muscle atrophy, the endocrine and motor functions of skeletal muscle are impaired. The mechanism of acupuncture to prevent and treat skeletal muscle atrophy is not only related to classical protein synthesis and decomposition, but also involves apoptosis, autophagy, muscle satellite cell proliferation and differentiation, muscle fiber type conversion, neuromuscular junction conduction, and cell energy metabolism conversion.
5.Effects of acupuncture at opposite acupoints on expression of hepatocyte growth factor in rats with skeletal muscle contusion.
Anning ZHANG ; Siqin HUANG ; Chenglin TANG ; Ao LUO ; Dandan ZHAO ; Ruiqi GAO ; Chengfang TAN ; Huiyu AN ; Mengjia WU ; Mang YU
Chinese Acupuncture & Moxibustion 2018;38(1):59-64
OBJECTIVETo observe the effects of acupuncture at opposite acupoints on expression of hepatocyte growth factor (HGF) in rats with skeletal muscle contusion, and to explore the mechanism of acupuncture at opposite acupoints on skeletal muscle contusion.
METHODSFifty-four Sprague Dawley (SD) rats were randomly divided into a blank group (6 rats), a model group (24 rats) and an opposing needling group (24 rats). The model group and opposing needling group were further divided into 1-day subgroup, 3-day subgroup, 5-day subgroup and 7-day subgroup, 6 rats in each one. No intervention was given in the blank group, while the model of skeletal muscle contusion was established in the model group and opposing needling group by self-made contusion device. 24 hours after contusion, electroacupuncture (EA) was applied at "Zusanli" (ST 36) and the corresponding points ofpoints at health side for 15 min, once a day. The subgroups of opposing needling group were treated for 1 day, 3 days, 5 days and 7 days, respectively. No treatment was given in the model group. Samples were collected in the subgroups 1 day, 3 days, 5 days and 7 days after treatment. The morphological change of injured gastrocnemius muscle was observed by using microscope after HE staining. The positive cell rate of proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry. The expression levels of HGF protein and PCNA protein were observed by Western blot.
RESULTS① The results of HE staining showed that, 1 day after contusion, the inflammatory cells of gastrocnemius muscle in the opposing needling group were less than those in the model group; 3 days and 5 days after contusion, myoblasts and myotubes in the opposing needling group were more than those in the model group; 7 days after contusion, the neonatal muscle cells in the opposing needling group were more than those in the model group. ② The results of immunohistochemistry showed that, 1 day, 3 days and 5 days after contusion, the positive cell rate of PCNA in the opposing needling group was significantly higher than that in the model group (all<0.001); 7 days after contusion, the positive cell rate of PCNA in the opposing needling group was significantly less than that in the model group (<0.001). ③ The results of Western blot showed that, 1 day, 3 days and 5 days after contusion, the expression of HGF protein and PCNA protein in the opposing needling group was significantly higher than that in the model group (all<0.05); 7 days after contusion, the expression of HGF protein and PCNA protein in the opposing needling group was significantly lower than that in the model group (all<0.05).
CONCLUSIONAcupuncture at opposite acupoints could regulate the expression of HGF and promote the activation, proliferation, migration and differentiation of muscle satellite cells in rats with skeletal muscle contusion, which could speed up the process of skeletal muscle injury repair.
6.Massage relieves inflammation and oxidative stress and promotes autophagy after contusion of skeletal muscles
Ao LUO ; Chenglin TANG ; Siqin HUANG ; Dandan ZHAO ; Anning ZHANG ; Mengjia WU ; Huiyu AN ; Chenfang TAN
Chinese Journal of Physical Medicine and Rehabilitation 2018;40(6):407-413
Objective To observe the effects of massage on inflammation,oxidative stress and autophagy during the repair of acute contusion of skeletal muscles so as to explore its biological mechanisms.Methods Forty-two adult Sprague-Dawley rats were randomly divided into a control group (n =6),a model group (n =18),and a treatment group (n =18).Acute contusion of the gastrocnemius muscles of the rats in the model and treatment groups was inflicted using a home-made impactor.Beginning forty-eight hours later,15 minutes of massage was administered daily for two weeks.After one,7 and 14 days of the massage treatment,the injured gastrocnemius was resected from 6 rats of both the model and treatment groups.Morphological changes were observed using haematoxylin and eosin (HE) staining.The serum content of tumor necrosis factor alpha (TNF-α),interleukin1β (IL-1 β),C reactive protein (CRP) and prostaglandin E2 (PGE2) were detected using enzyme-linked immunosorbent assay (ELISA).The serum content of superoxide (SOD) and malondialdehyde (MDA) were detected using spectrophotometry.The expression of microtubule-associated protein 1 light chain 3 (LC3),Bcl-2 homeodomain protein Beclin1 and ubiquitin binding protein P62 were detected using Western blotting.Results The HE staining showed more significant collapse and swelling of cells in the model group than in the control group at each time point.New muscle cells were observed at days 7 and 14 in the model group.At each time point,significantly better recovery was observed in the treatment group compared to the model group,with more new muscle cells and better cell morphology.According to the ELISA results,a significant increase in serum pro-inflammatory factors occurred in the model group compared to the control group and compared to the treatment group after one day and 7 days of treatment.The average serum content of SOD and MDA in the model group was significantly higher than in the control group,while the average serum content of SOD in the treatment group was significantly higher than in the model group and that of MDA was significantly lower.Western blotting showed a significant decrease in LC3 (Ⅱ/Ⅰ) and Beclin1,as well as a significant increase in P62 in the model group at each time point compared with the treatment group and the controls.Conclusion Inflammation and oxidative stress increase significantly in a skeletal muscle after injury,but autophagy decreases significantly.Massage can effectively reduce the inflammatory response and oxidative stress and promote autophagy,which leads to quicker repair of skeletal muscles.
7.The Optimization in Sensorimotor System in Dancers: Evidences from Resting State fMRI
Qi ZHAO ; Yingzhi LU ; Yingying WANG ; Chenglin ZHOU
Chinese Journal of Sports Medicine 2017;36(12):1081-1086
Objective To explore the functional improvement of dancers' sensorimotor system after years of dance training.Methods Twenty-three dancers(the dance group) of more than 6 years of dancing experience and twenty-one college students (the control group) without any dance experience were recruited in this study.Then the resting state functional magnetic resonance imaging(RS-fMRI) was conducted for both groups and the data were collected.Regional homogeneity (ReHo),fractional amplitude of low frequency fluctuation (fALFF) and functional connectivity (FC) were compared between the two groups.Results Compared to the control group,significant increase was observed in the ReHo of the bilateral postcentral gyruses,the left superior temporal gyrus,the right precentral gyrus and the middle occipital gyrus and fALFF in the bilateral precentral gyruses of the dance group.Moreover,the connection between the right precentral gyrus and left precentral gyrus and the FC between the right precentral gyrus and bilateral postcentral gyrus enhanced significantly in the dance group compared to the control group.Conclusions The functional modulation of dancers' sensorimotor system may be associated with the long-term dancing experience,which may lead to the changes in action perception,memory processing,motor learning and movement control to enhance the formation of the mode to observe,implement and adjust complex actions.Our study has provided a supporting evidence for dancing-induced brain plasticity.
8.Effects of heat-treated candida glabrata on the expression of Dectin-1,the production of IL-6 and TNF-α in rat tracheal epithelial cells
Xue ZHANG ; Xueping LUO ; Jian BAI ; Yuchun WANG ; Chenglin WU ; Ying ZHAO
Chongqing Medicine 2016;45(7):865-868
Objective To explore the effects of co‐cultured heat‐treated candida glabrata with rat tracheal epithelial (RTE) cells on the expression of Dectin‐1 and the production of IL‐6 and TNF‐α.Methods RTE cells in vitro were co‐cultured with heat‐treated candida glabrata bacteria liquid for 2 ,4 ,6 h ,while without co‐cultured RTE cells were used as control group .We observed the morphological changes of RTE cells ,detected the protein expressions of Dectin‐1 by Western blot ,used real‐time PCR to detecte the mRNA expressions of IL‐6 and TNF‐αand measured protein expression of IL‐6 and TNF‐αby ELISA .Results With the pass‐ing of time ,the RTE cells were damaged extensively and the expression of Dectin‐1 ,IL‐6 and TNF‐αbecame more and more signifi‐cant .Obviously ,there had significant difference in the expression of Dectin‐1 ,IL‐6 and TNF‐α between the co‐cultured 2 h group and the control group ,the co‐cultured 4 h group and the co‐cultured 2 h group ,the co‐cultured 6 h group and the co‐cultured 4 h group (P<0 .05) .Conclusion RTE cells have natural immune function .The Dectin‐1 involves in the recognition of heat‐treated Candida glabrata ,activating secretion of IL‐6 and TNF‐αand mediating inflammatory reaction .IL‐6 plays a negative regulation role .
9.De-noising of Impedance Cardiography Differential Signal and Detection of the Feature Points Based on Wavelet Transformation.
Yundong ZHAO ; Zhong JI ; Chenglin PENG ; Wei HUO
Journal of Biomedical Engineering 2015;32(2):284-289
Calculation of cardiac hemodynamic parameters is based on accurate detection of feature points in impedance cardiogram. According to these parameters, doctors can determine heart conditions, so it is very important to accurately detect the feature point of impedance differential signals. This article presents a process in which we used wavelet threshold method to de-noise signals, and then detected the feature points after six layers wavelet decomposition by using bior3. 7. The experimental data were collected from healthy persons in our laboratory and twenty two clinical patients in Chongqing Daping Hospital by using KF_ICG instrument. The results indicated that this method could precisely detect feature points whether it was from healthy people or clinical patients. This helps to achieve the application of noninvasive detection cardiac hemodynamic parameters in clinical treatments by using impedance method.
Cardiography, Impedance
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Electric Impedance
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Heart
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physiology
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Hemodynamics
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Humans
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Wavelet Analysis
10.Expression of cerebral Kuppel-like factor 2 in focal cerebral ischemia-reperfusion injury in rats and intervention effect of nuclear factor kappa B inhibitor
Chenglin ZOU ; Weijun CHEN ; Jing FANG ; Xiaoshun SUN ; Yazhou ZHAO ; Jun TU
Chinese Journal of Cerebrovascular Diseases 2015;(2):83-87
Objective To investigate the expression of Kuppel-like factor 2( KLF2 )after focal cerebral ischemia-reperfusion( I/R)injury in rats and the intervention effect of nuclear factor kappa B ( NF-κB)inhibitor. Methods Sixty healthy male SD rats were randomly divided into a sham operation group,an I/R group,and a NF-κB inhibitor group( n=20 in each group). A focal cerebral I/R model was induced by the intraluminal suture method,and NF-κB inhibitor( pyrrolidinedithio carbamate,PDTC)was given to intervene. The observation time points were 6,12,24,and 48 hours after I/R. Reverse transcription-polymerase chain reaction(PCR)and Western blot were used to measure KLF2 mRNA and protein expression in ischemic brain tissue. Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of serum tumor necrosis factorα( TNF-α),and they were compared among groups. Results Compared with the sham operation group,the expression levels of KLF2 mRNA and protein in I/R group in the ischemic brain tissue at each time point were averagely decreased( the relative expression levels of KLF2 mRNA:0. 46 ± 0. 03 vs. 0. 82 ± 0. 04,0. 30 ± 0. 04 vs. 0. 78 ± 0. 05,0. 18 ± 0. 04 vs. 0. 76 ± 0. 02,0. 26 ± 0. 02 vs. 0. 81 ± 0. 04,respectively;the relative expression levels of KLF2 protein:0. 46 ± 0. 04 vs. 0. 80 ± 0. 02,0. 30 ± 0. 02 vs. 0. 79 ± 0. 02,0. 15 ± 0. 02 vs. 0. 77 ± 0. 01,0. 24 ± 0. 01 vs. 0. 79 ± 0. 02,respectively). They reached the lowest values at 24 hours after I/R,while the serum TNF-αlevels were increased. There were significant differences(all P<0. 05). After giving NF-κB inhibitor PDTC,the expression levels of KLF2 mRNA and protein at 6,12,24,and 48 hours after I/R were upregulated differently compared with the I/R group. The relative expression levels of KLF2 mRNA were 0. 61 ± 0. 04,0. 44 ± 0. 03,0. 34 ± 0. 02,and 0. 43 ± 0. 04, respectively. Those of KLF2 protein were 0. 60 ± 0. 02,0. 43 ± 0. 02,0. 33 ± 0. 01,and 0. 44 ± 0. 03, respectively,while the levels of TNF-αwere decreased. There were significant differences(all P<0. 05). There was a negative correlation between the KLF2 mRNA levels and the serum TNF-αlevels at each time point in the I/R group and the PDTC group( r= —0. 728 ,P<0. 05 ). Conclusions The expression levels of KLF2 mRNA in brain tissue are decreased after I/R,and it is negatively correlated with the serum TNF-α levels. It may be involved in the pathological process of I/R by NF-κB pathway mediated inflammatory reaction.

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