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ObjectiveTo observe the effects of Sinisan on behaviors and NOD-like receptor protein 3 （NLRP3） inflammasomes of depressed rats induced by chronic unpredictable mild stress （CUMS） and further explore the anti-depressant mechanism of Sinisan. MethodFifty male rats were randomly divided into a normal group， a model group， an NLRP3 inhibitor （MCC950） group （10 mg·kg-1）， and low- （2.5 g·kg-1） and high-dose （5 g·kg-1） Sinisan groups， with 10 rats in each group. The depression model was induced by 42 d CUMS in rats except for those in the normal group. Drug intervention was performed on the 22nd day of modeling by gavage in the Sinisan groups and by intraperitoneal injection in the MCC950 group. Except for the MCC950 group， the remaining four groups received 10 mg·kg-1 physiological saline by intraperitoneal injection， while the rats in the model group， the normal group， and the MCC950 group were administered with 3 mL of physiological saline by gavage. Twenty-one days later， the sucrose preference test and open field test were performed. Western blot was used to detect the protein expression of NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， cysteinyl aspartate-specific protease-1 （Caspase-1）， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， ionized calcium-binding adapter molecule 1 （Iba1）， and CD68 in the hippocampus of rats in each group. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） in the hippocampus of rats. Nissl staining and TUNEL were used to assess the pathological changes and apoptosis level in the hippocampal CA1 region of rats， respectively. ResultThe sucrose preference rate and consumption volume in the sucrose preference test， the total distance， the percentage of central movement distance， and the percentage of residence time in the open field test of rats in the model group were lower than those in the normal group （P<0.01）. Compared with the model group， the Sinisan groups and the MCC950 group showed improved depression-like behaviors， apoptosis level in the hippocampal CA1 region， and neuron loss to varying degrees. Sinisan could reduce the levels of IL-1β， IL-18， Bax， Iba1， and CD68 in the hippocampus （P<0.05， P<0.01）， increase the level of Bcl-2 （P<0.05， P<0.01）， and inhibit the protein expression of NLRP3， ASC， and Caspase-1 related to NLRP3 inflammasomes （P<0.05， P<0.01）. ConclusionSinisan can improve the depression-like behaviors and pathological damage of hippocampal neurons in CUMS-induced rats， and the mechanism may be related to the inflammatory response mediated by the NLRP3 inflammasome signaling pathway.
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Objective:To observe the effect of modified Shuyuwan in amyloid precursor protein/ presenilin 1 （APP/PS1） dementia mice on cognitive and memory impairment and to explore its mechanism. Method:The 40 APP/PS1 mice were divided into model group （given Physiological saline）， low and high-dose modified Shuyuwan （14，64 g·kg<sup>-1</sup>）group， and donepezil group （1 mg·kg<sup>-1</sup>） and 10 wild mice were set as the blank control group （given Physiological saline）. All of the mice were administered intragastrically for 35 days. The memory and space exploration ability of mice was detected by Morris water maze， the morphology of mouse hippocampal neurons were observed by Nissl staining. The deposition of <italic>β </italic>amyloid 1-42（A<italic>β</italic><sub>1-42</sub>） in mouse hippocampus was detected by immunohistochemistry， and the expression of ionized calcium-binding adapter molecule 1（Iba1）， a marker of hippocampal microglia （MG） and Nitric oxide synthase（iNOS）， a marker of actived MG， were detected by immunofluorescence. The protein expression of NLR family pyrin domain containing 3（Nlrp3）， Apoptosis-associated speck-like protein containing a Caspase-recruitment domain （ASC）， cysteine protease-1（Caspase-1）and interleukin-1 beta （IL-1<italic>β</italic>） were detected by Western blot， and the expression of IL-1<italic>β</italic>， tumor necrosis factor-<italic>α</italic>（TNF-<italic>α</italic>）and interleukin-18 （IL-18） mRNA were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Result:Compared with the blank control group， the memory and space exploration ability of the model group were significantly reduced （<italic>P</italic><0.05）， the number of hippocampal neurons decreased， the deposition of A<italic>β</italic><sub>1-42</sub> increased， the markers of actived MG Iba1，iNOS increased， the protein expression of Nlrp3， ASC， Caspase-1， IL-1<italic>β</italic> increased significantly （<italic>P</italic><0.05）， and the mRNA expression of IL-1<italic>β</italic>， IL-18， and TNF-<italic>α</italic> increased significantly （<italic>P</italic><0.05）. Compared with model group， the Chinese medicine group can improve the APP/PS1 mice's space exploration ability and memory ability （<italic>P</italic><0.05）， increase the number of hippocampal neurons， reduce A<italic>β</italic><sub>1-42</sub> deposition， reduce the activation of MG， and reduce the protein expression of Nlrp3， ASC， Caspase-1 and IL-1<italic>β</italic> （<italic>P</italic><0.05）， and reduced the expression of IL-1<italic>β</italic> mRNA （<italic>P</italic><0.05）. Conclusion:Modified Shuyuwan can reduce the expression of IL-1<italic>β</italic> and other inflammatory factors in the hippocampus of APP/PS1 mice by inhibiting the Nlrp3/ASC/Caspase-1 pathway， and relieve nerve inflammation and pathological injury of AD.
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Objective:To observe the effect of quadriceps femoris spasticity on the movement parameters in stroke patients during obstacle crossing. Methods:From October, 2017 to November, 2018, 20 stroke patients were divided into spasticity group (n = 11) and non-spasticity group (n = 9) based on the score of modified Ashworth Scale (MAS) of quadriceps femoris. A 10-camera 3D motion analysis system and two force plates were used to synchronously measure the movement parameters of the patients during obstacle crossing of 15 cm high, such as step length, step width, anterior-posterior velocity of the center of mass (COMAPV) and medio-lateral velocity of the center of mass, toe-obstacle distance of unaffected limb, toe-obstacle clearance of affected limb, heel-obstacle distance, double support phase, and the swing phases of affected and unaffected limb. Results:Compared with the non-spasticity group, the COMAPV decreased as both affected and unaffected limb above the obstacle in the spasticity group (F > 10.006, P < 0.01), as well as the toe-obstacle distance and step length before obstacle crossing (F > 13.456, P < 0.01); while, the double support phase and the step width after obstacle crossing increased (F > 4.533, P < 0.05). Conclusion:The quadriceps femoris spasticity may make the strategy of obstacle crossing more carefully for stroke patients, and less efficiently.
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The central nervous system can produce a variety of neuroimmune factors including interleukin-6. This article reviewed the expression and signaling pathways of interleukin-6 and its receptors in the central nervous system, and advances in interleukin-6 in the regulation of central nervous system related diseases, cognitive behaviors and synaptic function, which suggested that interleukin-6 involves in various physiological or pathological functions in the central nervous system and affects central nervous system in multiple layers such as protein expression, signal transduction, neurological function, and synaptic transmission. Interleukin-6 is expected to be a biological marker in the specific state of the central nervous system. In addition, interleukin-6 can regulate the function of neurons and synapses and is an important molecule involved in synaptic transmission, synaptic plasticity, and learning and memory. Strengthening the research on the biological function and mechanism of interleukin-6 and timely regulating the interleukin-6 expression will provide a new perspective for the treatment of the central nervous system related diseases.
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The central nervous system can produce a variety of neuroimmune factors including interleukin-6. This article reviewed the expression and signaling pathways of interleukin-6 and its receptors in the central nervous system, and advances in interleukin-6 in the regulation of central nervous system related diseases, cognitive behaviors and synaptic function, which suggested that interleukin-6 involves in various physiological or pathological functions in the central nervous system and affects central nervous system in multiple layers such as protein expression, signal transduction, neurological function, and synaptic transmission. Interleukin-6 is expected to be a biological marker in the specific state of the central nervous system. In addition, interleukin-6 can regulate the function of neurons and synapses and is an important molecule involved in synaptic transmission, synaptic plasticity, and learning and memory. Strengthening the research on the biological function and mechanism of interleukin-6 and timely regulating the interleukin-6 expression will provide a new perspective for the treatment of the central nervous system related diseases.
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Emotional disorder is one of the main clinical symptoms of autism spectrum disorder(ASD),which is related to the lack of emotional awareness,social cognition and alexithymia. It is often manifested as difficulty in recognizing,distinguishing and processing emotional information of oneself and others,resulting in making inappropriate emotional reactions. Children and adolescents with ASD often participate in school bullying as the perpetrator,victim,or victim-perpetrator,and this brings about a series of negative physical and mental effects on them. Bullying prevention should not only include interventions for core symptoms and comorbidities of ASD,but also involve building partner empathy and social skills,teacher responsibility and supportive services,parental involvement,and social integration.
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For women planning pregnancy after tubalsterilization,they have to choose tubal recanalization or vitro fertilization(IVF).The important factors fordetermining the successful pregnancy after recanali-zation are the age of patient,the remaining length oftube,the type of sterilization initially performed and thetechnique of tubal recanalization.For women 40 years whoare with electrocoagulation as the method of steriliza-tion,they are suitable for IVF.Nevertheless,for the restones,there is no evidence showing which strategy islikely to be more effective.
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A series of novel benzimidazole and benzothiazole derivatives were designed and synthesized as inhibitors of SIRT1-SIRT3. The target compounds were synthesized from potassium O-ethyldithiocarbonate through a three-step route. The structures of the obtained compounds were elucidated by 1H NMR and HR-MS. Of all compounds, six showed potent SIRT2-inhibitory activities with IC50 values ranging from 2.8 to 21.2 μmol·L-1. Among them, compound 10c displayed the most potent SIRT2-inhibitory activities (IC50 = 2.8 μmol·L-1), with more than 35-fold selectivity over SIRT1 and SIRT3 (IC50>100 μmol·L-1).
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<p><b>OBJECTIVE</b>To assess nutritional status and define gender- and age-specific handgrip strength (HGS) cut-point values for malnutrition or nutritional risk in elderly inpatients.</p><p><b>METHODS</b>A cross-sectional study of 1,343 elderly inpatients was conducted in the Chinese PLA General Hospital. Nutrition Risk Screening (NRS 2002) and Subjective Global Assessment (SGA) were administered. Anthropometric measurements and blood biochemical indicators were obtained using standard techniques. The gender- and age-specific receiver operating characteristic (ROC) curves were constructed to evaluate the HGS for nutritional status by SGA and NRS 2002. Sensitivity, specificity, and areas under the curves (AUCs) were calculated.</p><p><b>RESULTS</b>According to NRS 2002 and SGA, 63.81% of elderly inpatients were at nutritional risk and 28.22% were malnourished. Patients with higher HGS had an independently decreased risk of malnutrition and nutritional risk. The AUCs varied between 0.670 and 0.761. According to NRS 2002, the optimal HGS cut-points were 27.5 kg (65-74 years) and 21.0 kg (75-90 years) for men and 17.0 kg (65-74 years) and 14.6 kg (75-90 years) for women. According to SGA, the optimal HGS cut-points were 24.9 kg (65-74 years) and 20.8 kg (75-90 years) for men and 15.2 kg (65-74 years) and 13.5 kg (75-90 years) for women.</p><p><b>CONCLUSION</b>Elderly inpatients had increased incidence of malnutrition or nutritional risk. HGS cut-points can be used for assessing nutritional status in elderly inpatients at hospital admission in China.</p>
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Asian People , Hand Strength , Physiology , Inpatients , Nutritional Status , PhysiologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of silencing ADP-ribosylation factor 6 (Arf6) on the proliferation, migration, and invasion of prostate cancer cell line PC-3 and the possible molecular mechanisms.</p><p><b>METHODS</b>Three Arf6-specific small interfering RNA (siRNA) were transfected into cultured prostate cancer cell line PC-3. Arf6 expression was examined by real-time PCR and Western blotting. MTT assay, wound healing assay, and Transwell migration and invasion assay were used to observe the effect of Arf6 silencing on the proliferation, migration, and invasion ability of PC-3 cells. The levels of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), ERK1/2, p-AKT, AKT and Rac1 were detected by Western blotting.</p><p><b>RESULTS</b>Transfection of siRNA-3 resulted in significantly decreased Arf6 mRNA and protein expression with inhibition rates of (91.88±3.13)% and (86.37±0.57)%, respectively. Arf6 silencing by siRNA-3 markedly suppressed the proliferation, migration and invasion of PC-3 cells and reduced the expression levels of p-ERK1/2 and Rac1.</p><p><b>CONCLUSION</b>Silencing of Arf6 efficiently inhibits the proliferation, migration, and invasion of PC-3 cells in vitro, and the underlying mechanisms may involve the down-regulation of p-ERK1/2 and Rac1.</p>
Subject(s)
Humans , Male , ADP-Ribosylation Factors , Genetics , Metabolism , Cell Line, Tumor , Cell Movement , Down-Regulation , Mitogen-Activated Protein Kinase 1 , Metabolism , Mitogen-Activated Protein Kinase 3 , Metabolism , Neoplasm Invasiveness , Prostatic Neoplasms , Pathology , RNA Interference , RNA, Messenger , Genetics , Metabolism , RNA, Small Interfering , Genetics , Real-Time Polymerase Chain Reaction , Transfection , Wound Healing , rac1 GTP-Binding Protein , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the association of maternal body composition and dietary intake with the risk of gestational diabetes mellitus (GDM).</p><p><b>METHODS</b>A total 154 GDM subjects and 981 controls were enrolled in a prospective cohort study in 11 hospitals from May 20, 2012 to December 31, 2013. Bioelectrical impedance analysis and dietary surveys were used to determine body composition and to evaluate the intake of nutrients in subjects at 21-24 weeks' gestation (WG). Logistic regression analysis was applied to explore the relationships of maternal body composition and dietary intake with the risk of GDM morbidity.</p><p><b>RESULTS</b>Age, pre-pregnant body weight (BW), and body mass index (BMI) were associated with increased risk of GDM. Fat mass (FM), fat mass percentage (FMP), extracellular water (ECW), BMI, BW, energy, protein, fat, and carbohydrates at 21-24 WG were associated with an increased risk of GDM. In contrast, fat free mass (FFM), muscular mass (MM), and intracellular water (ICW) were associated with a decreased risk of GDM.</p><p><b>CONCLUSION</b>Maternal body composition and dietary intake during the second trimester of pregnancy were associated with the risk of GDM morbidity.</p>
Subject(s)
Adult , Female , Humans , Pregnancy , Asian People , Body Composition , Body Mass Index , Cohort Studies , Diabetes, Gestational , Epidemiology , Diet , Diet Surveys , Feeding Behavior , Pregnancy Trimester, Second , Risk FactorsABSTRACT
The purpose of this study is to systematically investigate the characteristics of absorption and metabolism of oxymatrine (OMT) using rat intestinal perfusion model. Ultra performance liquid chromatography (UPLC) and high performance liquid chromatography-electrospray ionization-quadrupole-time of flight mass spectrometry (HPLC-ESI(+)-Q-TOF-MS) were used to test absorption of OMT in intestine at 100, 200 and 400 µmol · L(-1). The absorption rate and permeability of OMT is not dependent on concentration, but through passive absorption in intestine (P > 0.05). In the rat intestine, the absorbed amount of OMT was significantly different in four sections of the intestine in an order of duodenum > jejunum > ileum > colon (P < 0.05). OMT is metabolized into two metabolites in duodenum and jejunum, and matrine (MT) is the major one.
Subject(s)
Animals , Rats , Alkaloids , Metabolism , Chromatography, High Pressure Liquid , Intestinal Absorption , Intestines , Metabolism , Quinolizines , Metabolism , Spectrometry, Mass, Electrospray IonizationABSTRACT
<p><b>OBJECTIVE</b>To investigate activation of brown adipose tissue (BAT) stimulated by medium-chain triglyceride (MCT).</p><p><b>METHODS</b>30 Male C57BL/6J obese mice induced by fed high fat diet (HFD) were divided into 2 groups, and fed another HFD with 2% MCT or long-chain triglyceride (LCT) respectively for 12 weeks. Body weight, blood biochemical variables, interscapular brown fat tissue (IBAT) mass, expressions of mRNA and protein of beta 3-adrenergic receptors (β3-AR), uncoupling protein-1 (UCP1), hormone sensitive lipase (HSL), protein kinase A (PKA), and adipose triglyceride lipase (ATGL) in IBAT were measured.</p><p><b>RESULTS</b>Significant decrease in body weight and body fat mass was observed in MCT group as compared with LCT group (P<0.05) after 12 weeks. Greater increases in IBAT mass was observed in MCT group than in LCT group (P<0.05). Blood TG, TC, LDL-C in MCT group were decreased significantly, meanwhile blood HDL-C, ratio of HDL-C/LDL-C and norepinephrine were increased markedly. Expressions of mRNA and protein of β3-AR, UCP1, PKA, HSL, ATGL in BAT were greater in MCT group than in LCT group (P<0.05).</p><p><b>CONCLUSION</b>Our results suggest that MCT stimulated the activation of BAT, possible via norepinephrine pathway, which might partially contribute to reduction of the body fat mass in obese mice fed high fat diet.</p>
Subject(s)
Animals , Male , Mice , Adipose Tissue, Brown , Adiposity , Dietary Fats , Pharmacology , Ion Channels , Genetics , Metabolism , Mice, Inbred C57BL , Mitochondrial Proteins , Genetics , Metabolism , RNA, Messenger , Genetics , Metabolism , Triglycerides , Chemistry , Pharmacology , Uncoupling Protein 1 , Weight LossABSTRACT
<p><b>OBJECTIVE</b>To investigate whether resveratrol (RES) plays a protective role in hypothermic preserved isolated rat hearts and whether it is mediated by regulation of silent information regulator protein-1 (Sirt-1) expression.</p><p><b>METHODS</b>The Langendorff model of isolated rat heart was used. After stored in different Celsior solution at 4 degrees C for 9 h, SD rat hearts were randomly divided into 7 groups: blank control group;9 h group (soley hypothermic preservation for 9 h); RES group (3, 10, 30 micromol/L RES treatment plus hypothermic preservation for 9 h ), niacinamide (NAM) group (40 micromol/L NAM added in Celsior solution plus hypothermic preservation for 9 h), RES + NAM group (30 micromol/L RES and 40 micromol/L NAM were added in Celsior solution plus hypothermic preservation for 9 h). The morphological changes of cardiomyocytes were detected by the HE staining with the light microscope. The mRNA and protein expression levels of Sirt-1 were detected by Real-Time PCR and Western blot respectively.</p><p><b>RESULTS</b>(1) Compared with the blank control group, myocardiocytes were injured remarkably in the 9 h group and the Sirt-1 mRNA and protein expression levels were decreased significantly (P < 0.01); (2) Compared with the 9 h group, rat myocardial injury was alleviated gradually in 3, 10, 30 micromol/L RES group and the Sirt-1 mRNA and protein expression levels were increased in a dose-dependent manner (P < 0.05); (3) The above protective effects of RES were attenuated by Sirt-1 inhibitor NAM.</p><p><b>CONCLUSION</b>RES can protect myocardiocytes from injury caused by long range hypothermic preservation and this protective effect maybe mediated by upregulation of Sirt-1 expression.</p>
Subject(s)
Animals , Male , Rats , Cryopreservation , Heart , Organ Preservation , Rats, Sprague-Dawley , Sirtuin 1 , Metabolism , Stilbenes , PharmacologyABSTRACT
Objective To investigate the status on health-related knowledge and skills among the college students. Methods 5070 Chinese students from 28 universities or colleges were sampled, using the multiple-stage stratified, purposive and convenient mixed sampling method. A cross-sectional investigation on health literacy was conducted with self-designed questionnaire, and SPSS 13.0 was used to statistically analyze the data. Results The average scores on health-related related knowledge and skills among the subjects was 74.139 ± 12.0223, with 38.4% on basic health-related literacy (scores≥80). The rate (1.1%) of passing the margin line set for the awareness on chronic disease prevention appeared to be the lowest. And there noticed significant differences (P＜0.05) in different regions, types, and genders on the basic health-related knowledge and skills as well as on the prevalence rates of total and each dimensional health-related literacy among universities and colleges. Regions and types of universities and colleges were the main influencing factors on the levels of health-related knowledge and skills among the college students. Conclusion The prevalence of basic health-related knowledge and skills was low and the prevalence rates of health-related knowledge and skills were differently distributed among student populations under study.
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To screen potential human soluble epoxide hydrolase (hsEH) inhibitors, a high-throughput screening model in 384-well microplate with total volume of 50 microL was established. Recombinant hsEH was cloned and expressed in E. coli. and its specific substrate PHOME was synthesized. The HTS model was based on fluorescence analysis with enhanced sensitivity and specificity (Z' = 0.65). A total of 47 360 samples (including 25 040 compounds and 22 320 natural products) were screened, of which 950 samples with inhibition greater than 80% were selected for further rescreening. Finally, two compounds with high inhibitory activity were identified, whose IC50 value were 8.56 and 4.31 micromol x L(-1), separately. The results indicated that the method was stable, sensitive, reproducible and also suitable for high-throughput screening.
Subject(s)
Drug Evaluation, Preclinical , Methods , Enzyme Inhibitors , Chemistry , Epoxide Hydrolases , Chemistry , Metabolism , Escherichia coli , Metabolism , High-Throughput Screening Assays , Methods , Inhibitory Concentration 50 , Recombinant Proteins , Metabolism , Reproducibility of Results , Sensitivity and Specificity , Spectrometry, Fluorescence , Methods , Substrate SpecificityABSTRACT
<p><b>OBJECTIVE</b>To investigate effects of medium- and long-chain fatty acid triacylglycerols (MLCT) on body fat and serum lipid in overweight and hypertriglyceridemic subjects.</p><p><b>METHODS</b>A double-blind, controlled clinical trial was carried out, in which 112 subjects with hypertriglyceridemia were enrolled and divided into two groups, there were 56 subjects in each group. One group was randomized to consume long-chain fatty acid triacylglycerol (LCT), and the other to MLCT. All volunteers were asked to consume 25 - 30 g test oil daily for consecutive 8 weeks. Anthropometric measurements of body weight, body fat weight, waist circumference(WC), hip circumference(HC), WHR (ratio of WC/HC), total fat weight, subcutaneous fat area, visceral fat area, and serum biochemical variables of glucose, total cholesterols(TC), triglycerides(TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C)were measured at the initial and final time of the study.</p><p><b>RESULTS</b>11 subjects were excluded from the study because of various reasons. Of the 101 included cases, there were 50 (male subject 34, 68.0%) and 51 (male subject 33, 64.7%) subjects left in LCT and MLCT group respectively. The proportion of men in MLCT (64.7%, 33/51) was not significantly different (chi(2) = 0.1227, P > 0.05) compared to those in LCT (68.0%, 34/50). The average age of MLCT was (54.2 +/- 12.5) which was not significantly different (t = 0.39, P > 0.05) compared to those in LCT (53.2 +/- 13.0); Body mass index (BMI) of MLCT was (25.9 +/- 3.3) kg/m(2), which was not significantly different (t = 0.08, P > 0.05) compared to those of LCT (25.9 +/- 2.4) kg/m(2). After consumption of test oil for 8 weeks, extent of decrease in BMI, percent of body fat, subcutaneous fat, serum TG and serum LDL-C in overweight subjects of MLCT were (-0.73 +/- 0.61) kg/m(2), (-1.53 +/- 1.32)%, (-16.29 +/- 19.25) cm(2), (-0.57 +/- 0.86) mmol/L and (-0.05 +/- 0.64) mmol/L respectively, those in overweight subjects of LCT were (-0.19 +/- 0.61) kg/m(2), (-0.58 +/- 1.02)%, (4.69 +/- 19.06) cm(2), (0.65 +/- 1.10) mmol/L and (0.38 +/- 0.58) mmol/L respectively, all of them were significantly different (the value of t were -2.70, -2.43, -3.20, -3.81 and -2.09 respectively, all of P value were less than 0.05).</p><p><b>CONCLUSION</b>Consumption of MLCT can reduce body fat weight and serum triacylglycerol and LDL-C in overweight hypertriglyceridemic subjects under an appropriate dietary regime.</p>