BACKGROUND:No uniform standard for constructing the animal model of exercise-induced myocardial ischemia injury results in the incomparability among research results and impedes the development of sport medicine especial y in the cardiovascular field;thereby, it is imperative to reach an agreement in constructing criteria.
OBJECTIVE:To explore the method of establishing the rat model of myocardial ischemia induced by running.
METHODS:Total y 96 female Sprague-Dawley rats were randomly divided into rest control group, isoprenaline group and 10 exercise groups (1-and 3-time moderate-intensity exercise groups, 1-, 2-and 3-week moderate-intensity exercise groups, 1-and 3-time high-intensity exercise groups, 1-, 2-and 3-week high-intensity exercise groups). After exhaustive exercise, myocardium was col ected for morphological observation by hematoxylin-eosin staining, serum levels of myocardial enzymes and cardiac troponin I were detected, and the expressions of Bcl-2 and Bax were detected by real-time PCR.
RESULTS AND CONCLUSION:(1) Hematoxylin-eosin staining showed that the damage degree was more severe with the time of exercise, and the high-intensity exercise groups were more severe than those in the moderate-intensity exercise groups. (2) The activity of serum glutamic-oxaloacetic transaminase and lactic dehydrogenase was significantly increased after 1-week moderate-intensity exhaustive exercise (P<0.05 or P<0.01). From the beginning of the 3-time high-intensity exhaustive exercise, the activity of glutamic-oxaloacetic transaminase and lactic dehydrogenase was significantly increased (P<0.05 or P<0.01). (3) Cardiac troponin I content change trend was basical y the same as glutamic-oxaloacetic transaminase and lactic dehydrogenase changes, but cardiac troponin I content in the moderate-intensity exhaustive exercise groups was significantly higher than that in the rest control group until 2 weeks. The Bcl-2/Bax ratios in al exercise groups were significantly lower than that in the rest control group (P<0.05 or P<0.01);those in the 1-and 3-time high-intensity exercise groups were significantly higher than in the isoprenaline group (P<0.05 or P<0.01);and those in moderate-intensity groups were higher than in the isoprenaline group (P<0.05 or P<0.01). (4) In conclusion, 2-week high-intensity and 3-week moderate-intensity exhaustive exercise can induce myocardial ischemia injury, and pathological analysis, serum levels of myocardial enzymes and cardiac troponin I can be used as the evaluation indexes, while apoptosis regulation genes just as the reference index.

Objectives To study the effect of mesenchymal stem cells on the aging rat kidney and to explore the underlying mechanism. Methods Rat models of senile kidney were built with hypodermic injection of D-galactose daily. Injections of MSCs of 3 × 10<'6>were given to each rat through vena caudalis and CFSE was used as a tracing label to detect the distribution of MSCs in vivo. After 24 h, rats were dissected and their kidneys were frozen for section. MSCs were observed with Fluophot and quantitative analysis of the various parameters of kidney was performed under a light microscope with B12000 image analysis system.The contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in serum and kidney were measured wtih hydroxylamine and chromatometry. The expression of VEGF and P16 mRNA in kidney tissue was detected with real-time PCR and Western blotting. Results MSCs was found homing in the rat kidney,and the glomerular size, sklerosis-rate and the average cell count of glomerulus in the treated group were different from those of the model group (P<0.05). In the treated group, the activity of SOD was significantly higher and the content of MDA was lower in serum and kidney than that in the model control group (P<0.05). The expression of VEGF mRNA and protein in the kidneys of MSCs group increased significantly as compared with the model group (P<0.05). The expression of P16 mRNA and protein in the kidney of MSCs group decreased significantly compared with the model group (P<0.05). Conclusion MSCs can increase the expression of VEGF while decrease the expression of P16, so as to play a key role in the anti-aging on rat kidney.

Objective To observe the efficacy and side effects of exemestane in postmenopausal breast cancer patients with bone metastasis.Methods One hundred and ten postmenopausal breast cancer patients with bone metastasis were treated with exemestane 25 mg.Results In the evaluable data from 110 patients,the complete remission(CR)was encountered in 7 cases,partial remission(PR)in 28 cases,with a total response rate of 31.8％ ;Thirty nine patients had stabled diseases for more than 24 weeks.It produced a clinical benefit (CR + PR + SD)over 24 weeks in 74 cases(67.3％).Diseases progressed in 12 of the cases(10.9％).The patients with positive ER and PR status had a higher chance to be benefited from the treatment than those with negative receptor status.The clinical efficacy was not correlated with treatment history,pathological subtypes and bone,liver,lung and lymph node metastasis(x2 =0.045,0.078,0.200,P ＞ 0.05).No severe adverse effects were observed.Conclusion Exemestane is effective to treat bone metastasis of breast cancer with minor adverse reactions and good tolerability.

Objective:To evaluate the effect and safety of monoclonal antibodies to calcitonin gene-related peptide and its receptor (CGRP-mAbs) on migraine.Methods:Database of PubMed, Embase, Cochrane, CNKI, Wangfang digital journals were searched for randomized controlled trials (RCTs) of CGRP-mAbs in treatment of migraine. Quality of enrolled literature was assessed by the software of Review Manager 5.3 and software of StataMP14 was employed to conduct meta analysis.Results:A total of 13 RCTs were included, including 6 218 adult migraine patients (experimental group: 2 679 patients, placebo group: 3 539 patients). Meta analysis suggested that CGRP-mAbs for preventive treatment of migraine significantly reduced the monthly migraine days from baseline (standardized mean difference (SMD)=-0.35, 95% CI-0.4--0.3) and monthly acute migraine-specific medication consumption from baseline (SMD=-0.38, 95% CI-0.43--0.32), as compared with placebo group. CGRP-mAbs for preventive treatment of migraine significantly increased the ≥50% reduction from baseline in migraine days per month ( RR=1.65, 95% CI 1.54-1.76). The adverse events were similar between the CGRP-mAbs group and placebo group ( RR=1.06, 95% CI 1.01-1.10). Conclusion:CGRP-mAbs are effective and safe for preventive treatment of migraine.

Objective To investigate the role of irisin in exercise-induced improvement of renal function in type 2 diabetic rats. Methods Forty male SD rats aged 4-6 weeks were randomized into normal control group, type 2 diabetes mellitus model group, diabetic exercise (DE) group and diabetic irisin (DI) group (n=8). The rats in DE group were trained with treadmill running for 8 weeks, and those in DI group were given scheduled irisin injections for 8 weeks. After the treatments, blood biochemical parameters of the rats were examined, and renal histopathology was observed with HE, Masson and PAS staining. Western blotting was used to detect the protein expression levels in the rats' kidneys. Results The diabetic rats showed significantly increased levels of fasting insulin, total cholesterol, triglyceride, serum creatinine and blood urea nitrogen with lowered serum irisin level (all P<0.05). Compared with those in DM group, total cholesterol, triglyceride, serum creatinine and blood urea nitrogen levels were decreased and serum irisin levels were increased in both DE and DI groups (all P<0.05). The rats in DM group showed obvious structural disorders and collagen fiber deposition in the kidneys, which were significantly improved in DE group and DI group. Both regular exercises and irisin injections significantly ameliorated the reduction of FNDC5, LC3-Ⅱ/Ⅰ, Atg7, Beclin-1, p-AMPK, AMPK and SIRT1 protein expressions and lowered of p62 protein expression in the kidneys of the diabetic rats (all P<0.05). Conclusion Both exercise and exogenous irisin treatment improve nephropathy in type 2 diabetic rats possibly due to irisin-mediated activation of the AMPK/SIRT1 pathway in the kidneys to promote renal autophagy.

Objective To investigate the role of irisin in exercise-induced improvement of renal function in type 2 diabetic rats. Methods Forty male SD rats aged 4-6 weeks were randomized into normal control group, type 2 diabetes mellitus model group, diabetic exercise (DE) group and diabetic irisin (DI) group (n=8). The rats in DE group were trained with treadmill running for 8 weeks, and those in DI group were given scheduled irisin injections for 8 weeks. After the treatments, blood biochemical parameters of the rats were examined, and renal histopathology was observed with HE, Masson and PAS staining. Western blotting was used to detect the protein expression levels in the rats' kidneys. Results The diabetic rats showed significantly increased levels of fasting insulin, total cholesterol, triglyceride, serum creatinine and blood urea nitrogen with lowered serum irisin level (all P<0.05). Compared with those in DM group, total cholesterol, triglyceride, serum creatinine and blood urea nitrogen levels were decreased and serum irisin levels were increased in both DE and DI groups (all P<0.05). The rats in DM group showed obvious structural disorders and collagen fiber deposition in the kidneys, which were significantly improved in DE group and DI group. Both regular exercises and irisin injections significantly ameliorated the reduction of FNDC5, LC3-Ⅱ/Ⅰ, Atg7, Beclin-1, p-AMPK, AMPK and SIRT1 protein expressions and lowered of p62 protein expression in the kidneys of the diabetic rats (all P<0.05). Conclusion Both exercise and exogenous irisin treatment improve nephropathy in type 2 diabetic rats possibly due to irisin-mediated activation of the AMPK/SIRT1 pathway in the kidneys to promote renal autophagy.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

ObjectiveTo explore the correlation between dryness and energy metabolism of Atractylodis Rhizoma， and to analyze the difference of medicinal properties between Atractylodes lancea and A. chinensis. MethodA total of 110 healthy SD rats were randomly divided into 11 groups， including normal group， volatile oil of A. lancea 1-5 group （S1-S5 group， doses of 447， 473， 442， 489， 496 mg·kg^-1） and volatile oil of A. chinensis 1-5 group （N1-N5 group， doses of 197， 118， 281， 222， 185 mg·kg^-1）， the administration volume was 0.01 mL·g^-1 with intragastric administration for 21 days. Dryness effect of A. lancea and A. chinensis on rats was evaluated by comparing the body weight， drinking water volume， urine volume， whole blood viscosity and pathological sections of submandibular gland stained with hematoxylin-eosin （HE）. The expression of aquaporin 2 （AQP2） in rat kidney was measured by immunohistochemistry， the mRNA expressions of cytochrome C oxidase subunit 7A2 （COX7A2） and succinate dehydrogenase （SDH） complex subunit D （SDHD） in liver tissue were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The contents of SDH， lactate dehydrogenase （LDH） and sodium ion-potassium ion-adenosine triphosphatase （Na⁺-K⁺-ATPase） in rat plasma were determined by colorimetry. The quality of A. lancea and A. chinensis was evaluated by coefficient of variation method， and Pearson correlation coefficient was used to analyze the correlation between dryness and energy metabolism. ResultCompared with the normal group， the amounts of drinking water and urine in volatile oil of A. lancea group and volatile oil of A. chinensis group increased， and the submandibular gland acini atrophied， the whole blood viscosity of rats in the volatile oil of A. lancea group increased significantly （P<0.01）， the expression levels of COX7A2 and SDHD mRNA， the activities of SDH， LDH and Na⁺-K⁺-ATPase increased significantly （P<0.01）， and the expression of AQP2 in kidney decreased significantly （P<0.01）. Compared with the normal group， the expression level of COX7A2 mRNA， SDH activity and whole blood viscosity in the volatile oil of A. chinensis group increased （P<0.05， P<0.01）， the AQP2 and SDH mRNA expression levels， LDH and Na⁺-K⁺-ATPase activities had no significant difference. The comprehensive score analysis of each index showed that the effect of volatile oil of A. lancea on dryness and energy metabolism was stronger than that of volatile oil of A. chinensis， and there was a positive correlation between dryness index and energy metabolism index. ConclusionThe two indexes show that medicinal properties of A. lancea is stronger than that of A. chinensis， and energy metabolism is closely related to the dryness of Atractylodis Rhizoma. It is suggested that it is reasonable to evaluate the dryness effect of Atractylodis Rhizoma from the perspective of energy metabolism， which can further enrich the evaluation indexes of medicinal properties.

ObjectiveTo study the differences in volatile oil content of bran-processed Atractylodes lancea and its standard decoction concentrate and freeze-dried powder， as well as the differences in the types and contents of chemical components in volatile oil， and to clarify the quality value transmitting. MethodTen batches of A. lancea rhizoma were collected and prepared into raw products and bran-processed products of A. lancea， standard decoction concentrate and freeze-dried powder of bran-processed A. lancea in order to extract the volatile oil， and the transfer rate of volatile oil in each sample was calculated. Quantitative analysis of the main chemical components（β-eudesmol， atractylon， atractylodin） in each volatile oil was performed by gas chromatography（GC） on the HP-5 quartz capillary column（0.32 mm×30 m， 0.25 μm） with a flame ionization detector（FID）， a split ratio of 10∶1 and a temperature program（initial temperature at 80 ℃， hold for 1 min， rise to 150 ℃ at 10 ℃·min^-1， hold for 10 min， rise to 155 ℃ at 0.5 ℃·min^-1， hold for 5 min， rise to 240 ℃ at 8.5 ℃·min^-1， hold for 8 min）. Cluster analysis and principal component analysis（PCA） were used to explore the overall differences in types and contents of chemical components between the standard decoction concentrate and freeze-dried powder. ResultThe transfer rates of volatile oil in the bran-processed products， standard decoction concentrate and freeze-dried powder were 70.51%， 1.57% and 40.90%， respectively. The average transfer rates of β-eudesmol， atractylon and atractylodin in the volatile oil of bran-processed A. lancea were 58.45%， 48.49% and 55.64%， respectively. In the standard decoction concentrate， only β-eudesmol and atractylodin were detected， and their average transfer rates were 0.22% and 0.10%， respectively. And only β-eudesmol was detected in the freeze-dried powder with the average transfer rate of 8.37%. The results of cluster analysis and PCA showed that there are obvious differences in the types and contents of chemical components between the standard decoction concentrate and freeze-dried powder. ConclusionThe quality value transmitting between bran-processed A. lancea and its standard decoction concentrate and freeze-dried powder is stable， and if the freeze-dried powder is selected as the reference material of dispensing granules， appropriate amount of volatile oil should be added back to make it consistent with the quality of the standard decoction concentrate.

Traditionally, Tripterygium hypoglaucum (Levl.) Hutch (THH) are widely used in Chinese folk to treat rheumatoid arthritis (RA). This study aimed to investigate whether the anti-RA effect of THH is related with the gut microbiota. The main components of prepared THH extract were identified by HPLC-MS. C57BL/6 mice with adjuvant-induced arthritis (AIA) were treated with THH extract by gavage for one month. THH extract significantly alleviated swollen ankle, joint cavity exudation, and articular cartilage destruction in AIA mice. The mRNA and protein levels of inflammatory mediators in muscles and plasma indicated that THH extract attenuated inflammatory responses in the joint by blocking TLR4/MyD88/MAPK signaling pathways. THH extract remarkably restored the dysbiosis of the gut microbiota in AIA mice, featuring the increases of Bifidobacterium, Akkermansia, and Lactobacillus and the decreases of Butyricimonas, Parabacteroides, and Anaeroplasma. Furthermore, the altered bacteria were closely correlated with physiological indices and drove metabolic changes of the intestinal microbiota. In addition, antibiotic-induced pseudo germ-free mice were employed to verify the role of the intestinal flora. Strikingly, THH treatment failed to ameliorate the arthritis symptoms and signaling pathways in pseudo germ-free mice, which validates the indispensable role of the intestinal flora. For the first time, we demonstrated that THH extract protects joint inflammation by manipulating the intestinal flora and regulating the TLR4/MyD88/MAPK signaling pathway. Therefore, THH extract may serve as a microbial modulator to recover RA in clincial practice.ver RA in clincial practice.
Mice ; Animals ; Gastrointestinal Microbiome ; Tripterygium ; Myeloid Differentiation Factor 88/genetics* ; Toll-Like Receptor 4/genetics* ; Mice, Inbred C57BL ; Arthritis, Experimental/drug therapy*