Treatment of Uncomplicated Recurrent Urinary Tract Infection with Chinese Medicine Formula: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate Chinese medicine (CM) formula Bazheng Powder () as an alternative therapeutic option for female patients with recurrent urinary tract infection (RUTI).@*METHODS@#A randomized double-blinded trial was performed. Eligible female patients with RUTI were recruited from one hospital and two community health centers. By using a blocked randomization scheme, participants were randomized to receive a CM formula (10 herbs) for 4 weeks or antibiotics for 1 week, followed by 3 weeks of placebo. Clinical cure rate and microbiological cure and recurrence after treatment were evaluated.@*RESULTS@#A total 122 eligible patients were enrolled, with 61 cases in each group. The clinical cure rate by the intentto- treatment approach was 90.2% for the CM group and 82.0% for the antibiotics group (P>0.05). Bacteria were cleared from 88.5% (54/61) of patients in the CM group and 82.0% (50/61) in the antibiotics group. The recurrence rate in recovered patients at the 6-month follow-up was 9.1% (5/61) and 14.0 (7/61) in the CM and antibiotics groups, respectively (P>0.05).@*CONCLUSION@#CM formula Bazheng Powder is a good alternative option for RUTI treatment. (Registration No. NCT01745328).

Multi-drug resistant uropathogenic Escherichia coli and its treatment by Chinese medicine / 中国结合医学杂志

<p><b>OBJECTIVES</b>To investigate the resistance and virulence profiles of uropathogenic Escherichia coli (UPEC) and its treatment by Chinese medicine (CM) Fuzheng Qingre Lishi Formula (, FQLF).</p><p><b>METHODS</b>UPEC strains were isolated from recurrent urinary tract infections (UTIs) patients. Patient sensitivities to 17 antibiotics were tested by the disk diffusion method. Virulence genes were screened by plolymerase chain reaction. A mouse model was constructed using a multi-drug resistant and virulent UPEC strain and treated with FQLF or the antibiotic imipenem. The treatment efficacy was evaluated by bacterial clearance from urine and the urinary organs.</p><p><b>RESULTS</b>A total of 90 UPEC strains were collected, and 94.4% of the isolates were resistant to at least 1 antibiotic. Approximately 66.7% of the UPEC strains were multi-drug resistant. More than one virulence gene was found in 85.6% of the isolates. The extended-spectrum β-lactamases (ESBL)-positive strains were more resistant than the negative ones. The virulence gene number was positively correlated with the resistance number (P<0.05). A mouse model was successfully constructed using UPEC10. Treatment with either FQLF or antibiotics significantly cleared bacteria from the mouse urine after 14 days. In the untreated control, the bacteria lasted for 28 days. FQLF treatment of the UTI mouse model greatly reduced the bacterial number in the kidney and bladder, but could not completely clear the bacteria.</p><p><b>CONCLUSIONS</b>Multi-drug resistance is common among UPEC isolates, and the resistance is positively related with virulence. FQLF could treat UPEC UTIs, but could not completely clear the bacteria from the host.</p>

Chinese medicine syndrome distribution of chronic hepatitis B virus carriers in immunotolerant phase / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore Chinese medicine (CM) syndrome distribution of chronic hepatitis B virus (HBV) carriers in immunotolerant phase (ITP).</p><p><b>METHODS</b>One hundred and eighty-five chronic HBV carriers in ITP, seen in the Third Affiliated Hospital of Sun Yat-sen University from May 2009 to December 2010, were admitted in an observational study under the guidance of CM. Patients' CM symptoms and signs, demographics, liver biochemistries, and qualitative HBV DNA were recorded in the questionnaires. CM syndromes were then differentiated to 15 detailed types and analyzed by generalization. Lastly, the location, pathogenic factors and nature of the disease were also assessed.</p><p><b>RESULTS</b>When CM syndrome patterns were differentiated to 15 types, there were 27 (15%) no syndrome cases, 94 (50%) single syndrome cases and 64 (35%) compound syndromes cases. The main detailed syndromes included Liver (Gan)-qi depression (LQD), Kidney (Shen)-qi deficiency (KQD), Spleen (Pi)-qi deficiency (SQD) and Kidney-yang deficiency (KYAD). After CM syndromes generalized to five types, their frequency was Spleen-Kidney deficiency (SKD)>LQD>inner dampness-heat retention (IDHR)>Liver-Kidney deficiency (LKD)>blood stasis blocking collateral (BSBC). SKD and LQD occupied 64%. The disease location included Liver, Gallbladder (Dan), Spleen, Stomach (Wei) and Kidney. The pathogenic factors were mainly qi stagnation, qi deficiency, yang deficiency, concurrently dampness-heat and blood stasis. The deficiency syndrome was more than excess syndrome in its nature.</p><p><b>CONCLUSIONS</b>Most of chronic HBV carriers in ITP have their CM syndrome, and the most common types are SKAD, LQD. This study suggests that the natural history may be improved through breaking the state of immune tolerance or shorten the time of ITP by strengthening Spleen-Kidney and reliving Liver qi.</p>

Chinese integrative medicine: translation toward person-centered and balanced medicine / 中国结合医学杂志

Chinese integrative medicine (CIM) focuses on the integration of conventional medicine (biomedicine) with Chinese medicine (CM). Although the CIM field has witnessed several advancements, the definition and classification of CIM is not quite clear, given that an independent theory system has not yet been established in this field. Therefore, future research and studies should focus on the following objectives: (1) emphasizing CM features, (2) improving CIM positioning, and (3) establishing CIM standards. These concerted efforts will help CIM be at par with international standards and criteria. With the development of CIM, the world will embrace a new medical system providing person-centered treatment with a balanced medicine approach.

Dingxin recipe ( ) prevents ischemia/reperfusion-induced arrhythmias via up-regulating prohibitin and suppressing inflammatory responses / 中国结合医学杂志

<p><b>OBJECTIVE</b>To identify the underlying mechanisms of the protective effects of Dingxin Recipe (: , DXR), a Chinese compound prescription that has been used clinically in China for more than 20 years, on ischemia/reperfusion (I/R)-induced arrhythmias in rat model.</p><p><b>METHODS</b>A total of 30 rats were randomly divided into three groups: sham group, I/R group, and DXR-pretreated I/R (DXR-I/R) group. Rats in the DXR-DXRI/R group were intragastrically administrated with DXR (12.5 g/kg per day) for consecutive 7 days, while rats I/in the sham and I/R groups were administrated with normal saline. Arrhythmias were introduced by I/R and electrocardiograms (ECG) were recorded. Two-dimensional (2-D) polyacrylamide gel electrophoresis and matrix-matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used to identify assisted differentially expressed proteins. Immunohistochemistry, real-time quantitative polymerase chain reaction (RQ-RQPCR), Western blot, and enzyme-linked immunosorbent assay (ELISA) were performed to analyze proteins PCR), obtained in the above experiments.</p><p><b>RESULTS</b>DXR significantly reduced the incidence and mean duration of ventricular tachycardia and ventricular fibrillation and dramatically decreased the mortality, as well as arrhythmia score, compared with those of the I/R group. Among successfully identified proteins, prohibitin (PHB) and heart fatty acid binding protein (hFABP) were up-regulated in DXR-pretreated I/R rats compared with those of the I/R rats. In addition, compared with the I/R group, the level of glutathione (GSH) was elevated accompanied by reduced expressions of interleukin-6 (IL-6) and neutrophil infiltration in I/R rats with DXR pretreatment.</p><p><b>CONCLUSIONS</b>DXR could alleviate I/R-induced arrhythmias, which might be related to increased expression of PHB. The enhanced expression of PHB prevented against the depletion of GSH and consequently inhibited apoptosis of cardiomyocytes. Furthermore, up-regulation of PHB might ameliorate I/R-induced cell death and leakage of hFABP by suppressing neutrophil infiltration and IL-6 expressions.</p>

Effect of Tongxinluo superfine on experimental anginal model (contraction of collaterals) in rat with endothelial dysfunction / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effect of Tongxinluo superfine (TXL) on experimental anginal model induced by Arginine Vasopressin in rats with endothelial dysfunction.</p><p><b>METHOD</b>First, the endothelial dysfunction rat model was made by methionine-induced hyperhomocysteinemia (HHcy). The thoracic aorta were excised, and acetylcholine (Ach)-induced endothelium dependent relaxation and sodium nitroprusside (SNP) induced endothelium-independent relaxation were measured. Total plasma homocysteine (Hcy) concentrations were measured with automated fluorescence polarization immunoassay (FPIA). Enzyme-linked immunosorbent assay (ELISA) was used to detect plasma von Willebrand factor (vWF) level. Plasma nitric oxide (NO) contents were assayed by method of nitrate reductase. Then, the rat model of collaterals contraction (model group) was established by AVP intravenous injection in rats with endothelial dysfunction and the S wave change (DeltaS) and T wave depression in Lead II ECG were used as the index of angina severity. The nitric oxide (NO) contents in serum and the expression of myocardium eNOS mRNA were measured.</p><p><b>RESULT</b>Ach (0. 1-1000 nmol L(-1))-induced endothelium dependent relaxation (EDR) of aortic rings was significantly decreased in HHcy group. The endothelium-independent relaxation induced by SNP (0.001-10 micromol L(-1)) was not significantly different between the two groups. Plasma homocysteine concentrations and vWF levels in rats treated with methionine were higher than those of control group, while NO contents were significantly decreased in HHcy group compared with control. The results showed that L-methionine intake induced hyperhomocysteinemia in rats. Impaired EDR, increased vWF and decreased NO suggested the exist of endothelial dysfunction. DeltaS of model group increased from 1 min to 5 min and T wave of model group depressed at 2 min compared with that of control after the administration of vasopressin (0.5 U kg(-1)). The intragastric administration of TXL inhibited vasopressin-induced S wave change at 4 min and 5 min and T wave depression from 30 s to 3 min after AVP injection. The NO contents in serum and the expression of myocardium eNOS mRNA of TXL group were increased compared with model group.</p><p><b>CONCLUSION</b>Experimental angina induced by AVP injection is more severe in rats with endothelial dysfunction. Tongxinluo Superfine can protect against collaterals contraction in rats maybe by increasing the NO contents in serum and the expression of myocardium eNOS mRNA.</p>

Effect of delayed preconditioning induced by Sini decoction on myocardial cell apoptosis and its mitochondrial mechanism / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of myocardial cell apoptosis during delayed preconditioning induced by Sini decoction (SND).</p><p><b>METHOD</b>SD rats were divide into four groups: control, sham, I/R and SND groups. The rats in I/R group, left anterior descending coronary artery (LAD) was occluded for 1h and reperfused for 1 h. The rats in SND group were pretreated with Sini decoction (5 g x kg(-1) x d(-1)) for three days, the last treatment was pretreated 24 h before the index occlusion. Cell apoptosis was measured by flow cytometry, cytochrome C and bcl-xl were detected by Western blotting and the activity of caspase-3 was detected by assay kit.</p><p><b>RESULT</b>As compared with I/R group, apoptosis rate of myocardial cell, the release of cytochrome C from mitochondria and the activity of caspase-3 were significantly decreased, and the expression of bcl-xl protein was elevated in SND group.</p><p><b>CONCLUSION</b>The delayed preconditioning induced by Sini decoction decreased myocardial cell apoptosis. The mechanism may be related to the inhibition of mitochondria signal pathway of apoptosis.</p>

Study on sini decoction in treatment of intestinal ischemia-reperfusion injury in rats: mechanism relating to oxygen radical and bcl-2 protein / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the protective effect of Sini decoction (SND) on intestinal mucosa in rats with intestinal ischemia reperfusion (I/R) and the mechanism relating to oxygen radical and Bcl-2 protein expression.</p><p><b>METHOD</b>Thirty-two SD rats of both sexes were randomly divided into 4 equal groups: (1) control group in which sham operation was performed; (2) model group in which intestinal I/R was produced by clamping super mesenteric artery(SMA) for 1 hour and declamping SMA for 3 hours; (3) SND low dose group in which SND(3 g x kg(-1) x d(-1)) was given via stomach tube for 3 days before operation; (4) SND high dose group in which SND(6 g x kg(-1) x d(1)) was given via stomach tube, for 3 days before operation. A strip of small intestine was taken from distal end of ileum for light microscopic examination, Chiu's score and the detection of intestinal water content (IWC). Apoptosis of intestinal mucosa cell was examined by TUNEL method. Superoxide dismutase (SOD) activity, malondisldehyde (MDA) concentration of intestinal mucosa were detected. The protein express of Bcl-2 of intestinal mucosa was analyzed by immunochemistory.</p><p><b>RESULT</b>Intestinal /R resulted in histopathological changes in intestinal mucosa, increased Chiu's scores, apoptosis index, IWC and MDA content, and reduced SOD activity and the protein expression of Bcl-2 significantly (P < 0.01). The pretreatment of SND could attenuate the above changes significantly (P < 0.01), but there was no significant difference for the above variables between SND low dose group and SND high dose group (P > 0.05). Apoptosis index was significantly negatively correlative to SOD activity in model group and two SND groups. There were significantly negative correlation between apoptosis index and protein expression of Bcl-2 in model group and SND low dose group.</p><p><b>CONCLUSION</b>SND can attenuate intestinal mucosa injury following intestinal U/R, which is related to reducing intestinal mucosa cell apoptosis by removing oxygen free radical and upregulating the protein expression of Bcl-2.</p>

Effects of external counterpulsation on shear stress and production of nitric oxide and cGMP in canines with myocardial infarction / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of external counterpulsation (ECP) on shear stress and signal transduction in canines with myocardial infarction.</p><p><b>METHODS</b>Nineteen healthy dogs were randomly divided into control, ischemia, and ischemia plus ECP groups. Myocardial infarction was induced in the latter two groups by ligation of the left anterior descending artery (LAD). Serum and aorta NO levels of the dogs were determined by modified nitrate reductase method, and serum and aorta cyclic guanosine monophosphate (cGMP) levels by radioimmunoassay.</p><p><b>RESULTS</b>The shear stress in the truncus brachiocephalicus decreased after LAD ligation, but increased significantly after 2 h of ECP treatment. Serum and aorta NO levels in ECP and control groups were significantly higher than those in the ischemic group (P<0.05). Serum and aorta cGMP levels in control group and ECP group after LAD ligation were also significantly higher than those in the ischemic group (P<0.05).</p><p><b>CONCLUSION</b>ECP can increase the shear stress and increase NO and cGMP levels in dogs with myocardial ischemia, which might be an important mechanism of ECP for protection of the ischemic myocardium.</p>

Effects of irbesartan on nitric oxide system in the heart of diabetic rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of irbesartan for heart protection and on heart nitric oxide (NO) system in diabetic rats.</p><p><b>METHODS</b>Thirty adult male Wistar rats were randomly divided into three equal groups, namely control group, diabetes group and irbesartan group. Streptozotocin (STZ, 50 mg/kg) was injected to the abdomen to induce diabetes in the rats. After treatment for 12 weeks, the rats were sacrificed and the urine volume, body weight, ratio of heart to body weight, plasma glucose and glycosylated hemoglobin (HbA1c) were measured. NO levels in the serum and myocardium were determined. Inducible nitric oxide synthase (iNOS) expression was determined by immunohistochemistry, and iNOS mRNA detected by RT-PCR.</p><p><b>RESULTS</b>Urine volume, ratio of heart to body weight, plasma glucose, HbA1C, NO levels in the urine, blood and myocardium in diabetic and irbesartan rats were significantly greater than those of normal controls (P<0.05). The ratio of heart to body weight and NO levels of urine, serum and heart tissue in rats of irbesartan group were significantly decreased as compared with those of diabetes rats (P<0.05). Myocardium iNOS mRNA and protein expression decreased significantly in irbesartan group, but not in diabetes group.</p><p><b>CONCLUSIONS</b>The abnormality in NO and iNOS mRNA expression might be related to diabetic cardiomyopathy. Irbesartan can decrease iNOS mRNA and protein expressions and reduce NO levels in STZ-induced diabetic rats.</p>

Effects of Sini decoction on vascular stenosis after iliac artery balloon injury and oxidative stress in rabbits / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of Sini decoction (SND) in preventing vascular restenosis and protecting against oxidative stress after rabbit iliac artery balloon injury.</p><p><b>METHODS</b>Twenty-four male New Zealand albino rabbits were equally randomized into control group, model group and SND group. Rabbits in the control group were fed with common forage, and those in the model and SND groups with high-fat diet. Two weeks later, the iliac arteries of the rabbits in the latter two groups were subjected to balloon injury. Four weeks after the operation, the rabbits were killed and the vascular structure was observed by scanning electron microscope and optical microscope, with the serum cholesterol level, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level determined.</p><p><b>RESULTS</b>Scanning electron microscopy showed that the endothelial cell lining in the iliac artery of the control and SND group remain regular, but the arteries in the model group presented with desquamated and exposure of the collagen fibril beneath the endothelium. Optical microscope revealed narrowed vascular lumen, thicken intima and numerous arteriosclerotic plaques in the model group in comparison with the control group, whereas the vascular lumen and intima thickness remained basically normal in SND group. The levels of total cholesterol, low-density lipoprotein cholesterol and triglyceride were decreased with high-density lipoprotein cholesterol levels increased in SND group, which was not observed in the model group. The serum SOD activity was higher in the control group than in the model and SND groups, but SND group had higher serum SOD activity than the model group. The serum MDA level was lower in the control group than in the other two groups, but SND group had lower MDA level than the model group.</p><p><b>CONCLUSION</b>SND can alleviate intimal hyperplasia and vascular stenosis in injured rabbit iliac artery, possibly in relation to increased SOD activity and decreased lipid peroxidation as a result of SND treatment.</p>

Role of NF-kappaB in the induction of delayed preconditioning in rat heart by pretreatment with Sini decoction / 中国中药杂志

<p><b>OBJECTIVE</b>The present study was designed to investigate whether Sini decoction (SND) containing several chinese medicinal herbs, could induce delayed preconditioning-like effect in rat heart and the possible mechanism.</p><p><b>METHOD</b>In anesthetized open-chest Sprague Dawley rats, left anterior descending coronary artery (LAD) was occluded for 1 h and reperfused vided into four groups: Sham ( n = 8) group in which the surgical procedure was identical to other groups,but the LAD ligature was not ligated; I/R group (n = 8) in which the LAD of rat hearts was subjected to the index occlusion; IPC/SWOP group (n = 8) in which the LAD was occluded for three cycles of 5-minute episodes of preconditioning ischemia followed by 5-minute episodes of reperfusion 24 hours prior to the index occlusion; SND group (n = 8) in which rats were pretreated with Sini decoction (5 g x kg(-1) d(-1)) for three days, the last treatment was pretreated 24 h before the index occlusion. Myocardial infarct size, the activity of superoxide dismutase( SOD) and the content of malondialdehyde (MDA) in myocardial tissue were measured. The mRNA expression of MnSOD and Cu-ZnSOD were detected by RT-PCR. The expression of P65 subunit of NF-kappaB was determined by immunohistochemistry assay.</p><p><b>RESULT</b>As compared with I/R group, myocardial infarct size and the amount of MDA in myocardial tissue were significantly decreased, the activity of SOD and the mRNA expression of MnSOD were increased, the translocation of NF-kappaB was detected and furthermore the expression of NF-kappaB was significantly elevated in SND group as well as in IPC/SWOP group. The mRNA expression of Cu-ZnSOD was lowered in I/R, SND and IPC/SWOP groups, and there was no significant difference among these groups.</p><p><b>CONCLUSION</b>The results suggest that Sini decoction can induce delayed preconditioning-like effect in rat heart and the activation of NF-kappaB may play an important role in it.</p>

Protective effects of Sini decoction on adriamycin-induced heart failure and its mechanism: role of superoxide dismutase / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the role of superoxide dismutase (SOD) in Adriamycin (ADR)-induced heart failure and the protective effects of Sini decoction (SND).</p><p><b>METHOD</b>SD rats were randomly divided into three groups, control group, heart failure group and SND group. ADR was injected in the rats of heart failure group and SND group by caudal vein. After injection, the rats in SND group were given SND (3.75 g x kg(-1) x d(-1), p.o.). Three weeks later, cardiac function, content of malondialdehyde (MDA) of both myocardium and mitochondria and activity of Cu-Zn SOD and Mn SOD were measured. The mRNA expression of Cu-Zn SOD and Mn SOD were also detected by RT-PCR.</p><p><b>RESULT</b>Compared with control group, LVSP and +/- dp/dt max were obviously decreased, while LVEDP was markedly increased in the heart failure group. The mRNA expression and the activity of Cu-Zn SOD and Mn SOD in heart failure group were obviously lower than that in the controls'. In addition, the MDA content of both myocardium and mitochondria were clearly increased in heart failure rats. In SND-treated rats, the cardiac function, the activity and the mRNA expression of Cu-Zn SOD and Mn SOD were significantly elevated and the content of MDA was reduced, which had no statistic difference with the rats in control group.</p><p><b>CONCLUSION</b>The data suggest that oxidative stress is present in the mitochondria of myocardium in ADR-induced heart failure rats and it can be eased by SND. The mechanism may be closely related to SOD.</p>

Specific inhibiting effects of Ilexonin A on von Willebrand factor-dependent platelet aggregation under high shear rate / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Ilexonin A (IA), purified from the Chinese herbal medicine Maodongqing (Ilex pubescens Hook, et Arn) has been commonly used in south China to treat thrombotic disorders. In this study, we aimed to study the inhibiting effects and mechanism of IA on von Willebrand factor (vWF)-dependent high shear-induced platelet aggregation.</p><p><b>METHODS</b>vWF-dependent high shear (10,800 s(-1)) induced aggregation of platelets obtained from normal donors in the presence or absence of IA was measured by a modified cone-plate viscometer and shear-induced vWF binding was measured by quantitative flow cytometry with monoclonal antibody known to bind exclusively to the C-terminal domain of vWF (LJ-C3) directly labeled with fluorescein isothiocyanate (FITC). P-selectin surface expression was also measured by a similar method with FITC conjugated anti-P-selectin monoclonal antibody (WGA1).</p><p><b>RESULTS</b>Shear-induced platelet aggregation was inhibited by IA in a dose-dependent manner. The extent of aggregation decreased from (78.6 +/- 4.6)% in the absence of IA to (36.5 +/- 2.1)% in the presence of IA (3.3 mmol/L) (P < 0.0001, n = 9) with a high shear rate of 10800 s(-1). vWF binding and P-selectin expression were also inhibited by IA in a dose dependent manner. The number of binding FITC-LJ-C3 molecules increased after exposure of platelet-rich plasma to a high shear rate of 10800 s(-1) for 6 minutes, but this shear-induced increased binding platelet surface vWF molecules and P-selectin expression can be decreased in the presence of IA.</p><p><b>CONCLUSION</b>vWF binding and vWF mediated platelet activation, aggregation occurring under high shear rate were inhibited by IA. IA may be a unique antithrombotic drug inhibiting the vWF-GP Ibalpha interaction, and may thus facilitate drug design targeting arterial thrombosis.</p>

Experimental study on effect of sini decoction on myocardial endothelin in myocardial ischemic rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the molecular mechanism of effect of Sini Decoction (SND) on myocardial endothelin (MET) in myocardial ischemic rats.</p><p><b>METHODS</b>Sprague-Dawley rats were randomly divided into 3 groups, the normal control group, the ischemia group and the SND group. Myocardial ischemia was produced by pituitrin in the latter two groups. The content, immunohistochemical assay and gene expression of MET-1 were determined in all the three groups and compared.</p><p><b>RESULTS</b>The content of MET in the SND group was significantly lower than that in the ischemia group (P < 0.01). Immunohistochemical examination showed that MET-1 was mainly located at the cardiac muscle cells and vascular endothelial cells with the grey scale obviously lower in the ischemia group than that in the control group and the SND group (P < 0.01). While RT-PCR showed that the grey scale of PCR product band in the ischemia group was significantly higher than that in the other two groups (P < 0.01).</p><p><b>CONCLUSION</b>SND could significantly lower MET content, it may be related to the effect of SND in inhibiting MET-1 gene expression and protein synthesis.</p>