3.Negative modulation of NO for diaphragmatic contractile reduction induced by sepsis and restraint position.
Jian XIANG ; Su-Dong GUAN ; Xiang-He SONG ; Hui-Yun WANG ; Zhen-Yong GU
Journal of Forensic Medicine 2014;30(3):161-165
In practice of forensic medicine, potential disease can be associated with fatal asphyxia in restraint position. Research has demonstrated that nitric oxide (NO) and nitric oxide synthase (NOS) are plentifully distributed in skeletal muscle, contributing to the regulation of contractile and relaxation. In the current study, respiratory functions, indices of diaphragmatic biomechanical functions ex vivo, as well as NO levels in serum, the expressions of diaphragmatic inducible NOS (iNOS) mRNA, and the effects of L-NNA on contractility of the diaphragm were observed in sepsis induced by cecal ligation and puncture (CLP) under the condition of restraint position. The results showed that in the CLP12-18h rats, respiratory dysfunctions; indices of diaphragmatic biomechanical functions (Pt, +dT/dt(max), -dT/dt(max), CT, Po, force over the full range of the force-frequency relationship and fatigue resistance) declined progressively; the NO level in serum, and iNOS mRNA expression in the diaphragm increased progressively; force increased significantly at all stimulation frequencies after L-NNA pre-incubation. Restraint position 1 h in CLP12 h rats resulted in severe respiratory dysfunctions after relative stable respiratory functions, almost all the indices of diaphragmatic biomechanical functions declined further, whereas little change took place in NO level in serum and diaphragmatic iNOS mRNA expression; and the effects of L-NNA were lack of statistical significance compared with those of CLP12 h, but differed from CLP18 h group. These results suggest that restraint position and sepsis act together in a synergistic manner to aggravate the great reduction of diaphragmatic contractility via, at least in part, the negative modulation of NO, which may contribute to the pathogenesis of positional asphyxia.
Animals
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Asphyxia
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Diaphragm/physiology*
;
Muscle Contraction
;
Muscle, Skeletal
;
Nitric Oxide/metabolism*
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Rats
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Respiration Disorders
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Restraint, Physical
;
Sepsis
4.Biomechanical study on a net-fixation of Kirschner wire in treating depressed tibial plateau fractures.
Zhao-Xiang CHEN ; Wei ZHANG ; Hong-Hui HE ; Ming-Jiang LIU ; De-Hui ZENG
China Journal of Orthopaedics and Traumatology 2014;27(5):418-421
OBJECTIVETo evaluate the biomechanical properties of tibial plateau depressed fracture fixed with a net-fixation of Kirschner wires.
METHODSTwenty homemade fracture models were fixed with eight 1.5 mm Kirschner wires in a net-fixation; 20 homemade fracture models were fixed with two 3.5 mm cortical screws. Plane-compressed and dot-compressed test were made on each 10 models of the two groups. The maximal force of anti-ompress and stiffness were measured and evaluated.
RESULTSIn plane-compressed test,mean maximal force of anti-compress and stiffness for screw fixation was (1,925.31 +/- 444.26) N and (2.28 +/- 0.53) N/mm2, respectively, for net-fixation was (1,609.62 +/- 277.72) N and (1.90 +/- 0.33) N/mm2, respectively. There was no statistical difference between the two fixation methods (P > 0.05). In dot-compressed test,mean maximal force of anti-compress and stiffness for screw fixation was (411.13 +/- 233.88) N and (2.66 +/- 1.52) N/mm2,respectively,for net-fixation was (1,105.58 +/- 290.66) N and (7.18 +/- 1.89) N/mm2,respectively,the net-fixation was better than that of the screw fixation (P< 0.01).
CONCLUSIONTreatment of tibial plateau depressed fracture with a net-fixation of Kirschner wires is a biological fixation and is a reliably method.
Biomechanical Phenomena ; Bone Screws ; Fracture Fixation, Internal ; instrumentation ; Mechanical Phenomena ; Tibial Fractures ; surgery
5.Research progress of small molecular drugs targeting RNA
Xiao-li DU ; Hui-hui CHEN ; Xiang-yang YE ; Tian XIE ; Xing-rui HE
Acta Pharmaceutica Sinica 2022;57(10):2902-2913
At present, majority of the small molecular drugs used in clinics target proteins, they exert the efficacy through the binding to specific sites on the target protein. However, the "druggable" protein targets account for a small portion of the total number of proteins, and "non-druggable" proteins account for 80%, because of not having suitable drug binding sites. In the central rule, RNA is located in the upstream of proteins and controls the transcription of proteins. The research of small molecule drugs targeting RNA can solve the problem of protein "undruggable proteins" in some extent. This review summarizes the representative research achievements of small molecular drugs targeting RNA in recent years, and the screening methods applied to this field, with the focuses on the latest progress of small molecular drugs targeting novel coronavirus RNA.
6.Effect of pure total flavonoids from citrus on hepatic SIRT1/PGC-1alpha pathway in mice with NASH.
Zhi-Yun CHEN ; Jian-Shuang LI ; Jian-Ping JIANG ; Mao-Xiang YAN ; Bei-Hui HE
China Journal of Chinese Materia Medica 2014;39(1):100-105
OBJECTIVETo observe the effect of pure total flavonoids from Citrus (PTFC) on the hepatic fatty degeneration, inflammation, oxidative stress and SIRT1/PGC-1alpha expressions in mice with non-alcohol steatohepatitis (NASH), and discuss the action mechanism of PTFC on NASH.
METHODMice were given high-fat diet for 16 weeks to induce the NASH model. Since the seventh week after the model establishment, the mice were intervened with 100, 50 and 25 mg x kg(-1) x d(-1) PTFC for 10 weeks. The pathologic changes in hepatic tissues were observed with HE staining. The contents of TG, CHOL in hepatic tissue, as well as the levels of AST, ALT in serum were detected by using the biochemical process. The expression of SIRT1, PGC-1alpha and MnSOD mRNA in hepatic tissues were detected with Real-time PCR assay. SIRT1, PGC-1alpha protein and 8-OHdG expressions were determined with the immunohistochemical method. The SOD level in hepatic tissues was tested by the xanthine oxidase method. The MDA content in hepatic tissues was examined by the thiobarbituric acid method.
RESULTThe contents of TG, CHOL, NAFLD activity scores and ALT level in serum in hepatic tissues of mice in the model induced by fat-rich diet were obviously higher than that of the normal group (P < 0.010. The SIRT1, PGC-1alpha, MnSOD mRNA and protein expression in hepatic tissues were significantly lower than that of the normal group (P < 0.01). The expression of 8-OHdG and the content of MDA in hepatic tissues were obviously higher than that of the normal group (P < 0.01). After the intervention with different doses of PTFC, the NAFLD activity scores, the content of TG and the level of AST in serum were notably lower than that of the normal group (P < 0.01, P < 0.05); whereas the SIRT1, PGC-1alpha, MnSOD mRNA and protein expression were obviously higher than that of the normal group (P < 0.01, P < 0.05), with the significant decrease in the expression of 8-OHdG and the content of MDA (P < 0.01).
CONCLUSIONOxidative stress/lipid peroxidation enhancement in in NASH mice induced by high-fat diet may be related to the changes in SIRT1/PGC-1alpha signal transduction pathway. PTFC could enhance the anti-oxidant capacity in liver, relieve the damage of reactive oxygen during the fatty acid metabolic process, and prevent NASH from the occurrence and development by regulating the SIRT1/PGC-1alpha signal pathway.
Animals ; Citrus ; chemistry ; Fatty Liver ; drug therapy ; genetics ; metabolism ; Flavonoids ; chemistry ; pharmacology ; Inflammation ; drug therapy ; genetics ; metabolism ; Liver ; drug effects ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease ; Oxidative Stress ; drug effects ; genetics ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Sirtuin 1 ; genetics ; metabolism ; Transcription Factors ; genetics ; metabolism
7.Infect of pingshen decoction on serum HGF, Cys C and TGF-beta1 diabetic nephropathy in early stage.
Hui-Lan BAO ; Shang-He YE ; Shi-Xian LOU ; Xiao-Wen LU ; Xiang-Feng ZHOU
China Journal of Chinese Materia Medica 2014;39(6):1128-1131
Study the serum level of HGF, Cys C and TGF-beta1 in type 2 diabetic nephropathy (DN), the infect of Pingshen decoction on those index. Selected 69 cases of 2 type DN and randomly divided into therapy group (36 cases) and control group (33 cases). The therapy group were treated with Pingshen decoction 1 dose/d, bid po. The control group were treated with NephritisShu tablet, 6 tablet, tid po. 8 weeks was a course. Before and after treatment, we examine the serum level of HGF, Cys C and TGF-beta1 by ELISA and immunonephelometry, and compare with 30 cases of healthy control group. The study demonstrates that before treatment, the serum level of HGF in both groups were significantly lower than healthy control group (P < 0.01), but Cys C, TGF-beta1 were significantly higher (P < 0.01). After treatment, the serum level of HGF of both groups were increased. The serum level of HGF of therapy group were significantly higher than of control group (P < 0.01), but the serum level of Cys C and TGF-beta1 were significantly lower than control group (P < 0.01). The serum level of HGF was correlated negatively with Cys C,TGF-beta1. In control group, the UAER, urine beta2-MG and quantity of 24-hour urine protein were significantly decreased after treatment (P < 0.01). The index of urine of therapy group were significantly lower than control group (P < 0.01). Results indicate that test of serum level of HGF and Cys C,TGF-beta1 of diabetic nephropathy have important clinical significance. Pingshen decoction can effectively intervene in the serum level of HGF and Cys C, TGF-beta1 and index of urine.
Aged
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Aged, 80 and over
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Case-Control Studies
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Cystatin C
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blood
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Diabetic Nephropathies
;
blood
;
drug therapy
;
Drugs, Chinese Herbal
;
adverse effects
;
therapeutic use
;
Female
;
Hepatocyte Growth Factor
;
blood
;
Humans
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Male
;
Middle Aged
;
Transforming Growth Factor beta1
;
blood
9.Experimental study on intervention effect of Grifola frondosa on nonalcoholic steatohepatitis.
Xian-wei DAI ; Zhi-yun CHEN ; Mao-xiang YAN ; Bei-hui HE
China Journal of Chinese Materia Medica 2015;40(9):1808-1811
To study the preventive effect of Grifola frondosa on nonalcoholic steatohepatitis (NASH). The rat model of NASH was established by feeding high-fat diets for 12 weeks and intervened with 0.5 g · kg(-1) · d(-1) and 1.0 g · kg(-1) · d(-1) of C. frondosa powder suspensions. The degrees of hepatocyte fatty degeneration and inflammation were observed under the optical microscope with routine HE staining. The NAFLD activity scores (NAS) were calculated. Serum ALT, AST and hepatic TG and CHOL were tested by the biochemical method. The hepatic MDA was examined by thiobarbituric acid method. The hepatic SOD was tested by the xanthine oxidase test. The hepatic GSH-PX activity was determined by the dithio-nitrobenzoic acid method. Hepatic TNF-α and IL-6 were detected by the enzyme-linked immunosorbent assay (ELISA). The NASH model group induced by high-fat diets showed higher hepatic NAS, ser- um ALT, AST, CHOL and hepatic TG, CHOL, MDA, TNF-α, IL-6 (P < 0.01 or P < 0.05) and lower serum TG and hepatic SOD, GSH-PX (P < 0.01, P < 0.05) than the normal control group. After being intervened with different doses of G. frondosa, the NASH group revealed significantly lower hepatic NAS, serum ALT and hepatic TG, CHOL, MDA, TNF-α and IL-6 (P < 0.05) and higher hepatic SOD, GSH-PX (P < 0.05) than the model group. G. frondosa may prevent the further development of NASH by improving the disorder of lipid metabolism in rats with NASH induced by high-fat diets, relieving the level of oxidative stress and reducing the generation of inflammatory cytokines.
Animals
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Drugs, Chinese Herbal
;
administration & dosage
;
Grifola
;
chemistry
;
Humans
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Interleukin-6
;
metabolism
;
Liver
;
drug effects
;
metabolism
;
Male
;
Non-alcoholic Fatty Liver Disease
;
drug therapy
;
metabolism
;
Oxidative Stress
;
drug effects
;
Rats
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Rats, Sprague-Dawley
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Tumor Necrosis Factor-alpha
;
metabolism