1.Effect of transforming growth factor beta 1/Sma-and Mad-related protein signal pathway in diabetic nephropathy and related drugs:a review
Huiyu JIA ; Zhongnan LI ; Guangliang CHEN
Chinese Journal of Pharmacology and Toxicology 2016;30(3):266-271
Transforming growth factor-β1(TGF-β1)has become an important biological marker and therapeutic target of clinical progression of chronic kidney diseases. Sma- and Mad-related protein (Smad)is a downstream signal transduction protein of the TGF-β family. TGF-β1 activates Smad2 and Smad3 before increasing the transcription of connective tissue growth factors in the nucleus. Smad3 promotes mesangial cell proliferation,extracellular matrix accumulation,epithelial-mesenchymal transition, leading to renal fibrosis. However,Smad2 and Smad7 play a negative regulatory role by inhibiting renal fibrosis. TGF-β1 specific inhibitor (SB431542,etc.) has antifibrosis effect,most of which is in the preclinical stage. The drugs on the market that are effective for DN,such as benzodiazepines,atorvastatin, losartan,and pirfenidone,can inhibit the expression of TGF-β1,while tripterygium wilfordii,cordyceps sinensis,and berberine can delay the process of diabetic nephropathy by reducing TGF-β1 levels.
2. Prenatal dexamethasone exposure induces chondrodysplasia in offspring fetal female rats and its underlying mechanism
Chinese Journal of Pharmacology and Toxicology 2019;33(1):54-62
OBJECTIVE To investigate the effect of prenatal dexamethasone exposure (PDE) on chondrogenesis of female fetal rats and those of dexamethasone treatment on gene expression of chondrocytes, and to explore the underlying mechanism. METHODS ?In vivo, Wistar female ratswere conceived naturally, and the PDE group was sc given dexamethasone 0.2 mg-kg"1 once a day for 9-20 d after gestation (GD9-20). Pregnant rats were sacrificed on GD20( and cartilage samples of female fetal rats were collected. Tho morphology of cartilege was observed by HE and saffranin O staining. The expressions of aggrecan, O-xylosyltransfefase I (XylT-1), pi, 3-glucuronosyl transferase I [GlcAT-1).,4-galactosyttransterase 7, (GalT-I), insulin-like growth factor-1 (IGF-1), IGF-1 receptor (IGF-1R). protein kinase B {AKT) and activator protein I (AP-1) mRNA in cartilage tissues were examined by realtime quantitative PCR (RT-PCR). The expressions of XylT-I . GlcAT-I . GalT-I . IGF-1. AKT and AP-1 were detected by immunohistochemistry. In vitro, GD20 Wistar female fetal rats were used to extract chondrocytes from fetal knee joints. Dexamethasone (100 and 500 nmol-L"'). IGF-1 (100 ug-L"'). IGF-1 R inhibitor NVP-AEW541 (1 umol-L"), AKT inhibitor MK-2206 (1 pmol-L") and AP-1 inhibitor SR-11302 (1 umol-L∗') were treated for 24 h. The content of glycosaminoglycan (GAG) in the cefl supeRNAtant was detected by DMB staining. The expressions of XylT-1 , GlcAT-1 , GalT-1 , IGF-1 R, AKT and AP-1 mRNA were detected by RT-PCR. The expressions of XylT-I , GlcAT-I and GalT-I protein were detected by Western blotting. RESULTS (J) In vivo the results of HE and saffranin O staining showed that the number of articular chondrocytes of female fetal rats in PDE group was reduced, the arrangement of surface chondrocytes was disorderty. and staining of cartilage matrix became kghter and uneven. The protein and mRNA expression of cartilage, XylT-I , GlcAT-I , GalT-I and proteins related to IGF-1/AKT/AP-1 pathway were reduced in PDE group compared with normal control group (P<0.05, P<0.01). @ In vitro compared with the normal control group, the contcnt of GAG in the supeRNAtant of chondrocytes of female fetal rats was decreased (P<0.05). and the mRNA expressions of XylT-I , GlcAT-I, GalT-I and proteins related with IGF-1/AKT/AP-1 pathways were deceased (P<0.05). Compared with the dexamethasone 500 nmol-L"1 group, IGF-1 100 pg∗L" increased the mRNA expression levels of the above proteins {P<0.05, P<0.01). Compared with the normal control group, the protein and mRNA expressions of XytT-I , GlcAT-I and GalT-| in IGF-1 treatment group were increased, while those in IGF-1R/AKT/AP-1 inhibitor treatment groups were decreased (P<0.05, F<0.01). Compared with the SR-11302 group, there was no significant change in the protein and mRNA expression levete of XylT-I, GlcAT-1 and GalT-I after co-treatment with IGF-1. CONCLUSION PDE induceds chondrodysplasia in female fetal rats, which is related to the insufficiency of cartilage matrix synthesis induced by decreasing expression of glycosyltransferases mediated by low basic activity of IGF-1/AKT/AP-1 pathway.
3.Effects of Danzhi Jiangtang Capsule on CXCL9 and IL-8 in Diabetic Model Rats
Zhongnan LI ; Yuanyuan XIONG ; Li LI ; Zhaohui FANG
Chinese Journal of Information on Traditional Chinese Medicine 2014;(12):45-47
Objective To investigate the effects of Danzhi Jiangtang Capsule on CXCL9 and IL-8 in type 2 diabetic model rats, and discuss the mechanism in TCM intervention in type 2 diabetes. Methods Fifty male SD rats were randomly divided into 5 groups:normal control group, high-dosage group of Danzhi Jiangtang Capsule, low-dosage group of Danzhi Jiangtang Capsule, pioglitazone group and model group. Normal control group was fed with basal diet, while the other groups were fed with high fat diet. A single intraperitoneal injection of STZ of 35 mg/kg was employed to establish the animal model of diabetes mellitus. When the diabetic rodent model was built, high-dosage group of Danzhi Jiangtang Capsule and low-dosage group of Danzhi Jiangtang Capsule were treated with 1.08 g/(kg?d) and 0.54 g/(kg?d) by gavage, pioglitazone group was treated with 10 mg/(kg?d) by gavage, the blank group and the model group were treated with physiological saline 5 mL/(kg?d) by gavage for 8 weeks. CXCL9, IL-8 and blood glucose, and lipid in serum of rats were determined with double antibody sandwich method. Results Expressions of CXCL9 and IL-8 in model group increased significantly, compared with the normal control group (P<0.05, P<0.01). Expressions of CXCL9 and IL-8 in high and low dosage Danzhi Jiangtang Capsule group significantly decreased, the blood glucose and lipid also decreased, compared with model group (P<0.01). Conclusion Danzhi Jiangtang Capsule has inhibitory effects on the high expression of inflammatory factors in diabetes, and can also lower bloodglucose, and regulate blood lipid.
4. Balanced steady-state free precession MRA for diagnosing renal artery stenosis: Meta-analysis
Chinese Journal of Interventional Imaging and Therapy 2019;16(1):46-51
Objective" To investigate the value of balanced steady-state free precession (B-SSFP) MRA for diagnosing renal artery stenosis (RAS) with Meta-analysis. Methods PubMed, EMbase and Cochrane Library databases were searched. English studies assessed B-SSFP MRA diagnostic performance in RAS patients were reviewed. Quality assessment was conducted by adopting the Quality Assessment of Diagnostic Accuracy Studies-2 checklist. Statistical analysis was adopted using the software of Meta Disc 1.4 and Stata 12.0. The summary ROC (SROC) curve was drawn, and pooled AUC, sensitivity, specificity, diagnostic odds ratio were calculated. Results A total of 12 articles including 21 results were enrolled, which had highly heterogeneous by using random effects models. In B-SSFP diagnosing RAS, meta-analysis showed the pooled sensitivity was 0.85 (95%CI [0.81, 0.88], I2=56.8%) and pooled specificity was 0.96 (95% CI [0.95, 0.97], I2=85.3%), the area under the SROC curve was 0.964 4, the pooled diagnostic odds ratio was 137.94 (95%CI [84.75, 224.50]). Regression analysis showed that heterogeneity may be derived from the year of publication (P=0.038). Conclusion: B-SSFP MRA is accurate and reliable for diagnosing RAS, and may be the first choice in patients with renal insufficiency.
5.Effect of Danzhi Jiangtang Capsules on Serum Interleukin-18, Cystatin C and Relative Biochemical Indexes in Patients with Early Diabetic Kidney Disease
Zhongnan LI ; Fan ZHANG ; Chao MA ; Yuting XING ; Demei DOU
Journal of Guangzhou University of Traditional Chinese Medicine 2017;34(2):153-157
Objective To observe the effect of Danzhi Jiangtang Capsules(DJC) on serum interleukin-18 (IL-18),cystatin C (CysC) and relative biochemical indexes in patients with early diabetic kidney disease(DKD),and to explore its protective action on the kidney.Methods Sixty-two hospitalized patients with early diabetic nephropathy (period 11-Ⅲ) in Endocrinology Department of the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine were divided into western medicine group and DJC group,31 cases in each group.The patients in western medicine group received conventional hypoglycemic drugs,and DJC group received DJC based on the treatment for the western medicine group.Before and after treatment,we observed the levels of serum IL-18,CysC,fasting plasma glucose (FPG),2-hour postprandial glucose (2hPG),glycosylated hemoglobin (HbA1c),serum creatinine (SCr),blood urea nitrogen (BUN),microalbumin (mAlb),urinary albumin /creatinine ratio (UACR),and estimated glomerular filtration rate (eGFR).Results The total effective rate was 90.0% in DJC group and 76.7% in the western medicine group,there being significant difference between the two groups(P < 0.05).After treatment,the main traditional Chinese medical syndrome scores of DJC group were significantly lower than those before treatment,and the improvement was better than that of the western medicine group (P < 0.05 or P < 0.01).After treatment,the serum levels of IL-18,CysC,2hPG,SCr,BUN,mAlb,UACR in the two groups were significantly lower than those before treatment (P < 0.05 or P < 0.01),while eGFR level was higher than that before treatment (P < 0.05 or P < 0.01),and the improvement effect (except for BUN) in the DJC group was superior to that in the western medicine group(P < 0.01).DJC had an effect on lowering the FPG and HbA1c (P < 0.05 or P < 0.01 compared with those before treatment),and the western medicine had no obvious effect on the two indexes (P > 0.05).The results of Spearman correlation analysis showed that IL-18 was correlated with CysC,IL-18 and CysC were correlated with HbA1c,mALB and uACR.Conclusion DJC can protect renal function of patients with early diabetic nephropathy.
6.Clinical application of dorsal carpometacarpal reversed island flap with dorsal metacarpal nerve to reconstruct finger
Zhongnan ZUO ; Bin LI ; Yongjun DU ; Xueliang DU
Chinese Journal of Microsurgery 2000;0(02):-
Objective To investigate the clinical effect of dorsal carpometacarpal reversed island flap with dorsal metacarpal nerve to reconstruct finger. Methods We designed the dorsal reverse carpal and metacarpal island flaps with nerve by using the adjacent two dorsal matacarpal arteries as blood-supply and applied the stand of bone and tendon in waste finger or the free iliac transplantation to reconstruct the every sensory finger. Results Eighten cases were survived completely, and the skin degloving injuries of the finger in 3 cases. The maximum of the flap was 9cm by 8cm. Patients were followed up 3 months to 2 years,7 weeks later pain sense of reconstructed finger was recovered. Sensation over S3 amounts to 89% of the digits. Two-point-discrimination of the digits was 5-10mm. After the operation, the reconstructed finger obtained good appearance, the sensory recovery approach normally. The patients have ability to fulfil daily activities. Conclusion This method has advantages as follow:simple and practical,high survive rate,low impairment,sensible and good appearance.
7. Self-expanding metallic stent implantation in treatment of acute left-side malignant colorectal obstruction
Chinese Journal of Interventional Imaging and Therapy 2019;16(4):211-214
Objective To investigate the application value of self-expanding metallic stent (SEMS) implantation under fluoroscopy combined with endoscopy for acute left-side malignant colorectal obstruction. Methods Clinical date of 49 patients with left-side malignant colorectal obstruction who underwent SEMS implantation under fluoroscopy combined with endoscopy were retrospectively analyzed. Results Stents were implanted successfully in 48 patients. The technical success rate was 97.96% (48/49). One patient was transferred to emergency surgery because the guidewire could not pass through the stenosis. After stent implantation, colorectal obstruction relieved in 47 patients, while one patient was transferred to emergency surgery for unimproved obstruction. Postoperative perforation occurred in one patient after stent implantation, while a small amount of blood in excrement were found in 5 patients and then relieved after symptomatic treatment. Stent migration occurred in 2 patients. Totally 21 patients received tumor resection procedure after the symptoms of intestinal obstruction remission, and the success rate of surgery was 100% (21/21). Conclusion SEMS implantation under fluoroscopy combined with endoscopy is safe and effective to alleviate acute left-side malignant colorectal obstruction.
8. Analysis of false-negative results for 2019 novel coronavirus nucleic acid test and related countermeasures
Jin LI ; Guangming YE ; Liangjun CHEN ; Jiajun WANG ; Yirong LI
Chinese Journal of Laboratory Medicine 2020;43(0):E006-E006
In December 2019, a cluster of patients with pneumonia of unknown cause were linked to a seafood wholesale market in Wuhan, China. Some studies found that the virus was a new kind of virus which had never been found in the human body. Then, the virus was named 2019 Novel Coronavirus (2019-nCoV) by the World Health Organization (WHO). 2019-nCoV nucleic acid detection is one of the essential indicators of NCP (Novel Coronavirus Pneumonia). Recently, some false-negative cases in China-Japan Friendship Hospital and Hangzhou Hospital led the clinical doctors to question the value of the nucleic acid detection. In this paper, more than 3 000 results of 2019-nCoV detection in Zhongnan Hospital, Wuhan University were analyzed. Attention should be paid to the root cause of false-negative results and the related countermeasures should be taken.
9.Bilateral superior cervical ganglionectomy attenuates cardiac remodeling and improves cardiac function in pressure-overloaded heart failure mice.
Ge Rui LI ; Hang LI ; Zhan LYU ; Ze CHEN ; Yang Gan WANG
Chinese Journal of Cardiology 2021;49(4):345-352
Objective: To investigate the effect of bilateral superior cervical ganglionectomy on cardiac remodeling and function in pressure-overloaded heart failure (HF) mice. Methods: Pressure-overloaded HF mouse model was produced by severe thoracic aorta banding (sTAB). Bilateral superior cervical ganglionectomy (SCGx) was performed 2 weeks after sTAB. Twenty four 6-week-old male C57BL/6 mice were randomized divided into 4 groups (n=6 each): control group: sham sTAB+sham SCGx; denervated group: sham sTAB+SCGx; HF group: sTAB+sham SCGx; denervated HF group: sTAB+SCGx. Cardiac function was measured by echocardiography at week 0, 1, 2, and 4 after sTAB, respectively. All mice were sacrificed at the end of week 4 and heart tissues were harvested. HE and Masson staining were performed. Immunohistochemical staining (IHC) for tyrosine hydroxylase (TH), adrenergic receptor β1 (AR-β1) and CD68 was performed. Western blot was used to determine the protein expression level of TH, B type natriuretic peptide (BNP), and AR-β1. Results: Left ventricular ejection fraction (LVEF) declined continuously in HF group. LVEF was similar between denervated HF group and control group at various time points (P>0.05). LVEF was significantly higher in denervated HF group than in HF group at the end of week 4 (P<0.05). HE staining showed that cross sectional cardiomyocyte area was significantly larger in HF group than in control group and denervated HF group (P<0.05), which was similar between denervated HF group and control group (P>0.05). Masson staining showed that fibrosis level was significantly lower in denervated HF group than in HF group (P<0.05). IHC showed that TH+nerves and CD68+ macrophages were significantly increased in HF mice as compared to control mice (P<0.05), whereas this change was abolished in denervated HF group. AR-β1 was significantly down-regulated in HF group compared with control group (P<0.05), which was not affected by denervation (P>0.05). Western blot demonstrated that the expression level of TH and BNP was significantly higher in HF group compared with the control group (P<0.05), whereas this difference was diminished in denervated HF group (P>0.05). Conclusion: Bilateral superior cervical ganglionectomy can reduce sympathetic innervation and macrophage infiltration in pressure overloaded failure heart, thus attenuate cardiac remodeling and improve cardiac function.
Animals
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Cross-Sectional Studies
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Ganglionectomy
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Heart Failure
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Male
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Mice
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Mice, Inbred C57BL
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Stroke Volume
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Ventricular Function, Left
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Ventricular Remodeling
10.Comparison of invasive dynamic blood pressure between superior mesenteric artery and common carotid artery in rats
Rui-ning Liu ; Xiao-jun Wei ; Shao-ping Li ; Cheng Jiang ; Yan Zhao
World Journal of Emergency Medicine 2020;11(2):102-108
BACKGROUND: The purpose of this study was to identify the consistency of invasive dynamic blood pressure (BP) monitoring between the superior mesenteric artery (SMA) and the common carotid artery (CCA).
METHODS: Eight male Sprague-Dawley rats were cannulated in SMA and CCA simultaneously for BP monitoring, respectively. The abdominal aorta was prepared for the induction of BP change through clamping/de-clamping by a microvascular clip. The dynamic BP monitoring was performed by a polygraph system. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) values would be recorded during different time periods: the baseline (T1), the increasing period after clamping (T2), the platform period during clamping (T3), the decreasing period after de-clamping (T4), and the final platform period (T5). Three trials were performed on each rat with 15-minute intervals between consecutive monitoring.
RESULTS: Systolic BP showed no significant differences between SMA and CCA. However, significant difference was found in diastolic blood pressure except at T5 (P=0.534). Mean arterial pressure of two arteries were signifi cantly different only at T1 (P=0.015). The strength of association was significantly high between BP measurements through SMA and CCA (P<0.001). The Bland- Altman analyses showed that mean bias of MAP changed no more than 5 mmHg and standard deviation less than 8 mmHg during T2 and T4, respectively.
CONCLUSION: The study indicates SMA might be an alternative site for invasive BP monitoring during abdominal aorta occlusion and release, especially in cerebrovascular-related research.