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Objective:To investigate the application value of magnetic-controlled capsule endoscopy (MCE) for small intestine disease screening in physical examination population.Methods:Physical examination data of 1 230 individuals who received MCE examination from January to December 2019 in institute of Health Management were collected and retrospectively analyzed, and then divided into the gastrointestinal symptoms group and the group without gastrointestinal symptoms. Statistical analysis included the completion rate of MCE, the detection rate for small intestine disease in two groups, the relation between the gastrointestinal symptoms and small intestine diseases.Results:The mean age of the subjects was (54.4±17.3) years. The success rate of completion was 99.43%, and the detection rate of intestine diseases was 30.09%(368/1 230). Different genders and symptoms had no effect on the passage time of MCE through the small intestines, but the passage time of MCE through the small intestines in the age group younger than 50 years old [(242.9±88.7) min] was significantly less than in the age group greater than or equal to 50 years old [(336.4±112.1) min]( P<0.05). The detection rate of a duodenal bulbal ulcer and duodenitis was 1.73% (11/635) and 6.14% (39/635) respectively, in the symptomatic group, which were significantly higher than in the asymptomatic group 0.17%(1/595)及2.02%(20/595)( P<0.05). However, there was no significant difference in the detection rate of positive lesions between the two groups. Conclusion:There is a certain incidence of small intestinal diseases in people undergoing physical examinations. Magnetic-controlled capsule endoscopy can effectively complete the screening and diagnosis of small intestinal diseases while completing stomach examination, which is an effective tool for early diagnosis and prevention of small intestinal diseases in people undergoing physical examinations.
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ObjectiveTo observe the effects of the water extracts of Trichosanthis Radix-Polygonati Rhizoma at different ratios on glucose and lipid metabolism in KKAy mice with spontaneous type 2 diabetes and explore the mechanism of the extract in alleviating insulin resistance based on phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/forkhead box O1 （FoxO1） signaling pathway. MethodThe 8-week-old C57BL/6J male mice were taken as the normal control group， and KKAy male mice of the same age were randomly assigned into a model group， a metformin group， Trichosanthis Radix-Polygonati Rhizoma groups at the ratios of 1∶1 （Trichosanthis Radix 30 g， Polygonati Rhizoma 30 g）， 1∶3 （Trichosanthis Radix 15 g， Polygonati Rhizoma 45 g）， and 1∶5 （Trichosanthis Radix 10 g， Polygonati Rhizoma 50 g） according to blood glucose level and body weight， with 6 mice in each group. The administration lasted for 8 weeks， and the body weight （BW） and fasting blood glucose （FBG） of mice were recorded at the same time points of the 2nd， 4th， 6th， and 8th weeks， respectively. Oral glucose tolerance test （OGTT） was performed at the 7th week. After drug administration， the serum levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， and fasting insulin （FINS） were measured， and homeostasis model assessment-insulin resistance （HOMA-IR） index was calculated. The liver tissue samples were stained with hematylin-eosin （HE） and periodic acid-Schiff （PAS） for observation of the fat distribution and glycogen content. The protein levels of PI3K， Akt， p-Akt， FoxO1， and p-FoxO1 in the liver were determined by Western blot. ResultCompared with the normal group， the model group showed increased food intake， FBG， glucose tolerance， FINS， HOMA-IR， TC， TG， and LDL-C （P<0.01）， and down-regulated protein levels of PI3K， Akt， phosphorylaison （p）-Akt， FoxO1， and p-FoxO1 in the liver （P<0.01）. Compared with the model group， Trichosanthis Radix-Polygonati Rhizoma lowered FBG and HOMA-IR （P<0.05， P<0.01）. In particular， the combination at the ratio of 1∶3 showed the best performance （P<0.01） comparable to metformin. Furthermore， Trichosanthis Radix-Polygonati Rhizoma at different ratios lowered blood glucose at different time points of OGTT （P<0.05） and TC and LDL-C （P<0.01）. Additionally， the combination at the ratio of 1∶3 reduced TG （P<0.01）. The liver of mice in the drug administration groups showed regular morphology， with few lipid droplets and rich glycogen. Western blot showed that Trichosanthis Radix-Polygonati Rhizoma up-regulated the protein levels of PI3K and p-Akt， down-regulated the protein level of FoxO1， and up-regulated the protein level of p-FoxO1 （P<0.05）. ConclusionTrichosanthis Radix-Polygonati Rhizoma， especially at the ratio of 1∶3， lowered the FBG， TC， LDL-C， and HOMA-IR index， promoted liver glycogen synthesis， and reduced steatosis in KKAy mice， which may be related to the regulation of PI3K/Akt/FoxO1 signaling pathway in the liver.
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ObjectiveTo investigate the effect of Chuanshanlong granule on Toll-like receptor 4 （TLR4）/myeloid differentiation protein 88 （MyD88）/nuclear transcription factor -κB （NF-κB） signaling pathway， and to explore the mechanism of its treatment of autoimmune thyroiditis （AIT） in rats. MethodForty AIT models were established following excess iodine and injection of porcine thyroglobulin and Freund's adjuvant into Lewis rats for six weeks. Then the rats were randomly divided into the model group， Chuanshanlong granule low-， medium- and high-dose group （0.52， 1.03， 2.06 g·kg-1·d-1）， with ten in each group. Rats in the Chuanshanlong granule low-， medium- and high-dose groups were separately given 0.01 mL·g-1·d-1 Chuanshanlong granule， and those in the normal group and the model group were given the same volume of deionized water for eight weeks. Serum of rats was taken to measure thyroglobulin antibody （TgAb） and thyroid peroxidase antibody （TPOAb） by enzyme-linked immunosorbent assay （ELISA）， and the concentrations of free triiodothyronine （FT3）， free thyroxine （FT4） and thyroid stimulating hormone （TSH） were detected. The rat thyroid lobes were stained with hematoxylin and eosin （HE）， and the pathological changes were observed under light microscope. In addition， the relative expression of TLR4， MyD88， NF-κB protein and mRNA was determined by immunohistochemistry and real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the conditions in the normal group， the serum concentrations of TPOAb and TgAb （P<0.01） and FT3 and FT4 （P<0.01） increased and TSH decreased （P<0.01） in the model group. Compared with the conditions in the model group， the concentrations of TPOAb and TgAb in the Chuanshanlong granule treatment groups reduced （P<0.01）， and the concentrations of FT3 and FT4 were lowered （P<0.01） while TSH increased （P<0.01） in the Chuanshanlong granule high-dose group. HE staining showed that there was lymphocyte infiltration in the thyroid follicular space， a large number of destroyed or diminished follicular cavities， decreased colloid content， and thinned or destroyed follicular wall in the model group， while the thyroid lymphocyte infiltration in the Chuanshanlong granule treatment groups was significantly less and the structure of thyroid follicles was more complete than those in the model group. Compared with the normal group， the model group had up-regulated relative expression of TLR4， MyD88 and NF-κB protein （P<0.01） and mRNA （P<0.01）. Compared with the model group， the Chuanshanlong granule high-dose group had down-regulated relative expression of TLR4 protein and mRNA （P<0.05）， MyD88 protein （P<0.01） and mRNA （P<0.05）， and NF-κB protein and mRNA （P<0.01）. ConclusionChuanshanlong granule may play a therapeutic role in AIT by inhibiting the activation of TLR4/MyD88/NF-κB signaling pathway.
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Objective:To investigate the application value of magnetic-controlled capsule endoscopy (MCE) for small intestine disease screening in physical examination population.Methods:Physical examination data of 1 230 individuals who received MCE examination from January to December 2019 in Health Research institutes were collected and retrospectively analyzed, and then divided into the gastrointestinal symptoms group and the group without gastrointestinal symptoms. Statistical analysis in cluded the completion rate of MCE, the detection rate for small intestine disease in two groups, the relation between the gastrointestinal symptom and small intestine diseases.Results:The mean age of the subjects was (54.4±17.3) years. The success rate of completion was 99.43%, and the detection rate of intestine diseases was 30.09%(368/1 230). Different genders and symptoms had no effect on the passage time of MCE through the small intestines, but the passage time of MCE through the small intestine in the age group younger than 50 years old [(242.9±88.7) min] was significantly less than in the age group greater than or equal to 50 years old [(336.4±112.1) min]( P<0.05). The detection rate of a duodenal bulbal ulcer and duodenitis was 1.73% (11/635) and 6.14% (39/635), respectively, in the symptomatic group, which were significantly higher than in the asymptomatic group 0.17%(1/595)及2.02%(20/595)( P<0.05). However, there was no significant difference in the detection rate of positive lesions between the two groups. Conclusion:There is a certain incidence of small intestinal diseases in people undergoing physical examinations. Magnetic-controlled capsule endoscopy can effectively complete the screening and diagnosis of small intestinal diseases while completing stomach examination, which is an effective tool for early diagnosis and prevention of small intestinal diseases in people undergoing physical examinations.
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Objective@#To explore the relationship between parental self efficacy consistency with children s social development,and to provide a reference basis for promoting children s social development.@*Methods@#During September to October of 2019, cluster sampling method were used to select 905 children and their parents from 2 kindergarten (senior , mid and junior class) and 2 primary schools (grade one to grade three) in Bengbu. Children s social development and parental self efficacy were assessed by the Strengths and Difficulties Questionnaire(SDQ) and the parenting sense of competence Scale, respectively. Ordinal Logistic regression was used to analyze the relationship between parenting efficacy consistency with children s social development.@*Results@#Prevalence of emotional problems, conduct problems, hyperactivity attention inability，peer problems, and abnormal prosocial behtavior was 8.95%，6.30%， 18.01%, 14.03%，7.40% and 5.41%，respectively, which were negatively associated with parental self efficacy( P <0.01). Consistent parenting sense of competence, children s emotion, hyperactivity attention inability, moral behavior and prosocial behavior anomaly detection rate lowest, mother parenting self efficacy were higher than the father, children s enotion, conduct behavior, hyperactivity attention inability and prosocial behavior anomaly detection rate is highest, when the father parenting self efficacy was higher than that of mothers, Children s conduct behavior and hyperativity attention inability had the highest detection rate( Z =6.57, 7.58,7.25, 7.06, P <0.05). Children with higher maternal parenting self efficacy were more likely to develop emotional, conduct behavior, hyperactivity attention inability and prosocial behavior abnormalities, and children with higher father parenting self efficacy were more likely to develop conduct behavior and hyperactivity attention inability ( P <0.05).@*Conclusion@#Parental self efficacy and its consistency are related to child social development.It is suggested that parents should improve the parenting efficiency and the quality of companionship, optimize the family relations, and create a harmonious atmosphere.
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Objective@#To understand the current situation of the social development between only children and firstborn of young age, so as to provide a reference for the promotion of the social development of young children.@*Methods@#Stratified cluster sampling method was used to select 734 only children and firstborn children aged 3-9 in two kindergartens and two primary schools from grade 1 to grade 3 for questionnaire survey in Bengbu City. The content included the general information of children and their parents and the social assessment of children.@*Results@#The rate of emotional symptoms in firstborn children(27.8%) was higher than those of only children (17.6%)( χ 2=9.45, P <0.01). The results of univariate analysis showed that the rate of hyperactivity and inattention in social development of both only children and firstborns decreased with the increase of family socioeconomic status ( P < 0.05 ). Multivariate Logistic regression analysis of only children showed that only children with high economic status had a lower risk of hyperactivity and inattention and had a higher risk of peer interaction( P <0.05). The prosocial behavior of girls was better than that of boys in the aspect of social development of only children and firstborn children( OR =1.70, 2.85, P <0.05). For only children, the occurrence risk of being difficult was lower when the primary caregiver was parents than grandparents( OR =1.63, P < 0.05 ). For firstborn children, the risk of being difficult in nuclear families was lower than that in third generation families( OR = 2.14 , P <0.05). Multivariate analysis of the only child showed that boys had higher risk of hyperactive attention and less prosocial behavior than girls ( OR =2.24, 1.70, P <0.05), and a lower risk of developing mood disorders than girls( OR =0.57, P <0.05). The social development of only children varied among different grades, and the risk of abnormal prosocial behavior was lower with the increase of grades ( P <0.05).@*Conclusion@#Higer family social status is positively associated with children s social development level. But parents with high economic status should also avoid too much material and spiritual doting. Parents should strengthen their own learning to enhance the level of socialized education, raising siblings equally, improve the quality of parent child relationship, and promote the all round development of children s socialization level.
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OBJECTIVE：To evaluate the efficacy ，safety and econom y of donepezil in the treatment of Alzheimer ’s disease （AD），so as to provide evidence-based evidence for clinical rational drug use. METHODS ：Retrieved from PubMed ，Embase，the Cochrane Library ，CNKI，Wanfang database ，CBM and health technology assessment （HTA）organization websites ，systematic review/Meta-analysis，economic evaluation and HTA reports about donepezil in the treatment of AD were collected during the inception to Feb. 2021. Data extraction and quality evaluation were carried out for the literature that met the inclusion and exclusion criteria，and the research results were summarized and analyzed qualitatively. RESULTS ：A total of 26 studies were included ， including 15 systematic reviews/Meta-analysis ，and 11 economic studies ；HTA reports were not included. The results showed that in terms of effectiveness ，compared with placebo ，donepezil could significantly improve the cognitive function ，activity of daily life，mental behavior and overall function of AD patients （P＜0.05）；compared with rivastigmine ，donepezil could significantly improve cognitive function of AD patients （P＜0.05）；compared with galantamine ，donepezil could significantly improve cognitive function and overall function （P＜0.05），but there was no statistical significance in terms of improving mental behavioral symptoms（P＞0.05）；there was no statistical significance between donepezil and memantine in improving cognitive function ， psychobehavioral symptoms and activities of daily living in AD patients （P＞0.05），but donepezil was weaker than memantine in overall functional （P＜0.05）. In terms of safety ，there was no significant difference in the tolerance and mortality in patients using donepezil and placebo （P＞0.05）；donepezil was better tolerated than rivastigmine and galantamine （P＜0.05）；there was no significant difference in the incidence of ADR for donepezil compared with placebo ， metamine and other non-placebo mail：15201008872@163.com controlled drugs （P＞0.05）. Economic studies showed that # compared with rivastigmine ，placebo and no AD-related drug treatment，donepezil could prolong quality adjusted life years （QALY）and saved medical costs ，which was more cost-effective. Compared with conventional treatment for basic disease and memantine，although donepezil could prolong QALY ，whether it had economic advantages still needed to confirmed in combination with national or regional health resource conditions. CONCLUSIONS ：Donepezil is ralatively effective ，safe and economical in the treatment of AD.
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Objective:The response surface methodology (RSM) and Box-Behnken design were adopted to optimize the preparation for citrus oils β-cyclodextrin microspheres inclusion compound. And the physical characterization and heat stability were evaluated.Methods:The best preparation technology included inverse emulsion polymerization and saturated water solution method, with volatile oil weight ratio and microspheres, microspheres and water feeding ratio, inclusion temperature as impact factors, inclusion rate as the response value, establish regression model,. We explored the orange peel naphtha beta ring paste by microscopy, infrared spectroscopy (IR), differential scanning calorimetry (DSC) and heat stability test.Results:The best preparation technology included the essential oil with beta ring paste microspheres ( V: m), the ratio of 1:10, beta ring paste small ball and the ratio of water (m: V) for 1:15, and inclusion temperature for 41 ℃. The average encapsulation efficiency and the average rate of yield under optimized conditions were 62.21% and 85.24%, respectively. The physical characterization and thermal stability tests demonstrated that the β-cyclodextrin microsphere inclusion complex of volatile oil from Citrus was successfully prepared and the physical properties were stable. Conclusion:The preparation method of citrus oils β-cyclodextrin microspheres inclusion compound by using the response surface methodology.
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Abstract@#In recent years, the incidence of allergic diseases in children and adolescents has been on the rise globally, which has become an important public health problem. It is important to identify modifiable risk factors for allergic diseases in this group. In this paper, through research review on the association between sleep behavior and allergic diseases in children and adolescents, it is suggested that sleep deficiency, sleep disorder and sleep rhythm disturbance are closely related to children s allergic diseases, which provides a new concept for prevention of allergic diseases through sleep behavioral improvement.
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Objective@#To explore the characteristics of pain sensitivity of autism spectrum disorder (ASD), and to provide reference for clinical comprehensive intervention of ASD.@*Methods@#A case-control study was conducted to investigate the characteristics of pain sensitivity in 142 ASD children and 142 normal children using the items related to pain sensitivity in the Autism Treatment Evaluation Checklist (ATEC). In addition, two recognized ASD model mice (BTBR mice and model mice induced by VPA) were selected as experimental group. The thermal pain threshold and mechanical pain threshold of BTBR mice were measured by electroshock seizure threshold and Von Frey filament test, and the differences of pain characteristics between BTBR mice and control mice were compared, the thermal pain threshold of model mice induced by VPA (VPA rats) was measured by electroshock seizure threshold, and the differences between BTBR mice and control mice (Con) were compared.@*Results@#There was significant difference in pain sensitivity between ASD group and control group (χ 2=0.81，P<0.05), and the sensitivity of ASD children to pain was significantly lower than that of normal control children. The pain sensitivity of BTBR mice and C57BL/6 mice on the 42 nd day after birth was measured. The T-test analysis showed that the time taken for BTBR and C57BL/6 mice to retract their feet on the 42 nd day after birth (3.62±0.38,3.02±0.33)s (t=3.28,P<0.01), and the mechanical pain threshold (9.75±3.58,0.55±0.93)s (t=7.44,P<0.01). The detection of thermal stinging pain in VPA rats and con rats on the 9 th, 11 th, 13 th and 15 th day after birth was detected. The results of t test were as follows:P9(11.34±1.38,9.81±1.64)g, P11(11.37±1.98,9.36±1.11)g, P13(11.53±1.38,9.51±1.01)g and P15(12.05±2.91,8.74±1.60)g (t=-2.79,-2.25,3.95,3.95,P<0.05).@*Conclusion@#Compared with normal control children, ASD children show insensitivity to pain which is further supported by two types of animal models for ASD.
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Objective:To evaluate the systemic absorption and safety of multiple doses of topical tazarotene/betamethasone dipropionate cream in healthy subjects and patients with psoriasis.Methods:From September 2008 to April 2009, 12 healthy subjects collected from Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College were randomly and equally divided into tazarotene 0.15%/betamethasone dipropionate 0.15% cream group and tazarotene 0.2%/betamethasone dipropionate 0.2% cream group; these subjects were instructed to apply 0.03 g of the test drug per day on each of the 4 body sites, including the flexor aspects of bilateral forearms, waist and back, for 7 consecutive days, and venous blood samples were obtained before, and 1, 3, 5 and 7 days after the start of drug application. From October 2010 to August 2011, 60 patients with non-cephalic psoriasis collected from the Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College were randomly divided into 3 groups at a ratio of 3∶1∶1, i.e., tazarotene 0.05%/betamethasone dipropionate 0.05% cream group ( n = 36) and tazarotene 0.05% gel group ( n = 12) topically treated with a cream vehicle in the morning and the test drug at night, and betamethasone dipropionate 0.05% cream group ( n = 12) topically treated with the test drug twice a day (once in the morning and again in the evening) ; the treatment lasted 6 consecutive weeks, and venous blood samples were collected before, and 2, 4 and 6 weeks after drug application. Liquid chromatography-tandem mass spectrometry was performed to determine the concentrations of tazarotenic acid and betamethasone in plasma. During the trial, adverse events in the subjects were recorded, routine blood and urine examinations were carried out, and liver and kidney function were evaluated before and after treatment. Results:The plasma concentrations of tazarotenic acid and betamethasone in the 12 healthy subjects were below the lower limit of quantitation (0.04 μg/L) after 1-, 3-, 5- and 7-day treatment. After the consecutive treatment, tazarotenic acid and betamethasone were detected in 2 (5.56%) and 4 (11.11%) patients respectively at week 2, 4 or 6 in the tazarotene 0.05%/betamethasone dipropionate 0.05% cream group, and the highest plasma concentrations of tazarotenic acid and betamethasone were 0.112 and 0.201 μg/L respectively; in the betamethasone dipropionate 0.05% cream group, betamethasone was detected in 2 of 12 patients, and the highest plasma concentration of betamethasone was 0.112 μg/L. No test drug-related systemic adverse reactions or laboratory abnormalities were observed in any of the healthy subjects or patients.Conclusion:Multiple doses of topical tazarotene/betamethasone dipropionate cream has advantages of little systemic absorption, no long-term accumulation and good systemic safety.
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Objective:To evaluate the role of heme oxygenase-1 (HO-1)-induced endogenous protection in lipopolysaccharide (LPS)-caused apoptosis in rat alveolar macrophages and the relationship with endoplasmic reticulum stress.Methods:Alveolar macrophages of rats were randomized into 4 groups ( n=32 each) using a random number table method: control group (group C), LPS group (group L), Con siRNA group and HO-1 siRNA group. Cells were cultured normally in group C, and 10 μg/ml LPS was added to the culture medium in the other three groups. Con siRNA and HO-1 siRNA transfection was performed at 48 h before adding LPS in Con siRNA and HO-1 siRNA groups. At 24 h of treatment with LPS, MTT method was used to measure the cell viability, flow cytometry was used to determine the cell apoptosis rate, and Western blot was used to detect the expression of glucose regulatory protein 78 (GRP78), phosphorylated kinase receptor-like endoplasmic reticulum kinase (p-PERK), CCAAT/enhancer-binding protein homologous protein (CHOP), phosphorylated type I endoplasmic reticulum transmembrane protein kinase (p-IRE-1), phosphorylated stress-activated protein kinase (p-JNK) and caspase-12. Results:Compared with group C, the cell viability was significantly decreased, cell apoptosis rate was increased, and the expression of HO-1, GRP78, CHOP, p-PERK, p-IRE-1, p-JNK and caspase-12 was up-regulated in the other three groups ( P<0.05). Compared with group L, the cell viability was significantly decreased, cell apoptosis rate was increased, and the expression of HO-1 was down-regulated, and the expression of GRP78, CHOP, p-PERK, p-IRE-1, p-JNK and caspase-12 was up-regulated in group HO-1 siRNA ( P<0.05), and no significant change was found in each parameter in group Con siRNA ( P>0.05). Compared with group Con siRNA, the cell viability was significantly decreased, cell apoptosis rate was increased, and the expression of HO-1 was down-regulated, and the expression of GRP78, CHOP, p-PERK, p-IRE-1, p-JNK and caspase-12 was up-regulated in group HO-1 siRNA ( P<0.05). Conclusion:The mechanism of HO-1-induced endogenous protection is related to inhibiting endoplasmic reticulum stress and then reducing LPS-induced apoptosis in alveolar macrophages of rats.
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Objective:To evaluate the relationship between melatonin receptors and mitochondrial fission proteins and to clarify the mechanism of melatonin alleviating lipopolysaccharide(LPS)-induced damage to type Ⅱ alveolar epithelial cells of rats.Methods:The rat type Ⅱalveolar epithelial cells were seeded in 6-well plates at a density of 2×10 5 cells/ml and divided into 5 groups ( n=10 each) using a random number table method: control group (C group), LPS group (L group), LPS plus melatonin group (LM group), LPS plus melatonin receptor blocking group (LL group), and LPS plus melatonin plus melatonin receptor blocker group (LML group). The model of LPS-induced damage to cells was established by incubating with LPS 10 μg/ml for 24 h. Melatonin 0.1 mmol/L and/or melatonin receptor blocker luzindole 0.2 μmol/L was added in LM group, LL group and LML group.The concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay after the end of incubation.The mitochondrial respiratory control rate (RCR) was measured by GENMED purified mitochondrial RCR quantitative detection kit in each group.Western blot was used to detect the expression of dynamin-related protein 1 (Drp1) and mitochondrial adaptor fission 1 (Fis1). Results:Compared with C group, the concentrations of TNF-α and IL-6 in culture medium were significantly increased, RCR was decreased, and the expression of Drp1 and Fis1 was up-regulated in L, LM, LL and LML groups ( P<0.05). Compared with L group, the concentrations of TNF-α and IL-6 in culture medium were significantly decreased, RCR was increased, and the expression of Drp1 and Fis1 was down-regulated in LM group ( P<0.05), and no significant change was found in parameters mentioned above in LL group ( P>0.05). Compared with LM group, the concentrations of TNF-α and IL-6 in culture medium were significantly increased, RCR was decreased, and the expression of Drp1 and Fis1 was up-regulated in LML group ( P<0.05). Conclusion:The mechanism by which melatonin attenuates LPS-induced damage to type Ⅱ alveolar epithelial cells is related to activating melatonin receptors and inhibiting the expression of mitochondrial fission proteins in rats.
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Objective:To evaluate the relationship between heme oxygenase-1/carbon monoxide (HO-1/CO) signaling pathway and mitochondrial fission in lipopolysaccharide (LPS)-challenged alveolar type Ⅱ epithelial cells (AECⅡ) of rats.Methods:The cultured AECⅡ were subcultured and inoculated in 96-well plates (about 2 × 10 5 cells/ml) and divided into 7 groups ( n=12 each) using a random number table method: blank control group (group C), LPS group (group L), carbon monoxide release molecule-2 (CORM -2) + LPS group (group CL), HO-1 inducer hemin+ LPS group (group HL), HO-1 inhibitor ZnPP-Ⅸ+ LPS group (group ZL), CORM-2+ ZnPP-Ⅸ+ LPS group (group CZL) and hemin+ ZnPP-Ⅸ+ LPS group (group HZL). In group C, the cells were continuously incubated and received no treatment.Cells were incubated with LPS 10 μg/ml in group LPS. In CL, HL and ZL groups, cells were incubated with 100 μmol/L CORM-2 for 1 h, with 20 μmol/L hemin for 1 h and with 10 μmol/L ZnPP- Ⅸ for 0.5 h, respectively, and then the cells were incubated with 10 μg/ml LPS.In group CZL, the cells were incubated with 100 μmol/L CORM-2 for 1 h, then with 10 μmol/L ZnPP-Ⅸ for 0.5 h, and finally with 10 μg/ml LPS.In group HZL, the cells were incubated with 20 μmol/L hemin for 1 h, then with 10 μmol/L ZnPP-Ⅸ for 0.5 h, and finally with 10 μg/ml LPS.Cell viability was evaluated by methyl thiazolyl tetrazolium assay at 48 h of culture or incubation with LPS.The expression of HO-1, dynamin-related protein 1 (Drp1) and mitochondrial fission protein 1 (Fis1) was determined using Western blot. Results:Compared with group C, the cell viability was significantly decreased, and the expression of HO-1, Drp1 and Fis1 was up-regulated in other six groups ( P<0.05). Compared with group L, the cell viability was significantly increased, the expression of HO-1 was up-regulated, and the expression of Drp1 and Fis1 was down-regulated in CL and HL groups, the cell viability was decreased, HO-1 expression was down-regulated and the expression of Drp1 and Fis1 was up-regulated in group ZL ( P<0.05), and no significant change was found in the parameters mentioned above in CZL and HZL groups ( P>0.05). Compared with CL and HL groups, the cell viability was significantly decreased, HO-1 expression was down-regulated, and the expression of Drp1 and Fis1 was up-regulated in group ZL ( P<0.05). Conclusion:HO-1/CO signaling pathway can inhibit mitochondrial fission, which exerts endogenous protection when LPS induces injury to AEC Ⅱ in rats.
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Objective:To investigate the effect of Guilu Erxian Jiao (GEJ) on the negative feedback function of hypothalamic-pituitary-adrenal (HPA) axis and its possible mechanism in rats with post-traumatic stress disorder(PTSD).Methods:The PTSD rat model was established using single prolonged stress (SPS). Ninety six SD rats were randomly divided into control group (control), model group (SPS), GEJ group (GEJ) and paroxetine group (PRX) according to the random number table with 24 rats in each group. Except the control group, the rats in the other groups were constructed using the PTSD model. On the 8th day after the establishment of the model, the rats of the GEJ group (3.6 g/kg) and the PRX group (10 mg/kg) were respectively given the drug by gavage for 21 days. The rats in control group and SPS group were given the same amount of distilled water once a day for 21 days. After continuous administration for 21 days, 12 rats were randomly selected from each group for the dexamethasone suppression test (DST), then 6 rats were selected for the RT-PCR, and the remaining 6 rats were used for immunohistochemistry. The contents of plasma adrenocorticotrophic hormone (ACTH) were measured by Elisa. The expression levels of glucocorticoid receptor (GR), mineralocorticoid receptor (MR), adrenocorticotropic hormone releasing factor Ⅰ receptor (CRF1R) and adrenocorticotropic hormone releasing factor Ⅱ receptor (CRF2R) were detected by RT-PCR and immunohistochemistry.Results:(1) In DST, plasma ACTH level in SPS group was significantly lower than that in control group((145.89±19.41)μg/L, (203.59±35.78)μg/L, t=3.16, P<0.01), and that in the PRX group and GEJ group were significantly higher than that in SPS group((218.47±37.55)μg/L, t=3.98, P<0.01; (205.33±66.54)μg/L, t=3.26, P<0.01). (2) RT-PCR results showed that, in hippocampus, the GR mRNA and MR mRNA expressions in SPS group were significantly higher than those in control group((1.29±0.02), (1.00±0.06), t=6.88, P<0.01; (1.38±0.02), (1.00±0.05), t=7.97, P<0.01), and that in the GEJ group significantly decreased comparing to SPS group((0.96±0.07), t=7.87, P<0.01; (0.86±0.13), t=11.03, P<0.01). (3) Immunohistochemical results showed that, in hippocampus, the positive cell expressions of GR and MR in the SPS group were significantly higher than those in control group((84.33±12.82), (69.33±8.19), t=2.50, P<0.05; (77.33±6.65), (56.33±11.79), t=2.25, P<0.05), and that in the GEJ group significantly were lower than SPS group((68.33±4.55), t=2.67, P<0.05; (59.50±4.18), t=2.25, P<0.05). In amygdala, the positive cells expression of GR, MR and CRF1R in the SPS group significantly decreased compared with the control group((62.67±6.89), (77.17±10.70), t=3.10, P<0.05; (60.50±11.66), (91.83±15.63), t=3.43, P<0.05; (54.50±19.96), (88.17±22.43), t=2.31, P<0.05); and that in GEJ group significantly increased compared with the SPS group((74.33±5.85), t=2.11, P<0.05; (83.67±12.55), t=2.53, P<0.05; (88.67±16.28), t=2.35, P<0.05). Conclusion:GEJ can inhibit the enhanced HPA axis negative feedback function induced by SPS, which may be related to regulating expression of GR, MR and CRF1R in the hippocampus and amygdala.
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OBJECTIVE：To explore the mechanism of Hippophae rhamnoides in the treatment of Alzheimer ’s disease （AD）， and to provide theoretic reference for further exploring the material basis. METHODS ：TCMSP，Uniprot，GeneCards database were used to screen the active components of H. rhamnoides ，targets and AD-related target gene. The “ingredients-targets-related diseases”network was constructed by Cytoscape 3.7.1 software. STRING database was adopted to construct protein interaction （PPI）network，molecular docking was conducted between the potential targets with high degree values and active components of H. rhamnoides . The gene ontology （GO）analysis and Kyoto encyclopedia of genes and genomes （KEGG）pathway enrichment analysis were performed by Clue GO for the potential target of H. rhamnoides in the treatment of AD. Totally 50 mice were randomly divided into blank group ，model group [ D-galactose 120 mg/（kg·d），AlCl3 solution 20 mg/（mL·d）]，positive drug group [oxiracetam 260 mg/（kg·d）]，seabuckthorn oil extract group [ 1.6 g/（kg·d）]，seabuckthorn polyphenols group [1.6 g/（kg·d）]，with 10 mice in each group. The mice was given relevant medicine intragastrically and modeling agent ；blank group was given constant volume of distilled water intragastrically ，once a day ，for consecutive 60 d. The learning and memory abilities were detected by Morris water maze test ；the levels of immune factors in hippocampus tissue were measured by ELISA. Pathological morphology of hippocampus tissue was observed by HE staining. The mechanism of H. rhamnoides in the treatment of AD was validated preliminarily. RESULTS ：Totally 22 active components of H. rhamnoides （quercetin，kaempferol，isorhamnetin， β-carotene，β-sitosterol） may affect biological processes such as nuclear receptor activity ，lipopolysaccharide-mediated signal pathway，and may affect 114 methabolism pathways such as IL- 17 signal transduction pathway ，TNF signal transduction pathway by regulating 147 targets such as serine/threonine kinase coding protein （AKT1），amino terminal kinase （JUN）and mitogen activated protein kinase （MAPK1）. The results of molecular docking showed that binding scores of the main active components of H. rhamnoides and the main target proteins were all above 4.25，which showed good binding activity. Results of pharmacology experiment showed that H. rhamnoides extract could shorten the escape latency of AD model mice ，increased the times of crossing platform，relieved hippocampus injury of cerebral tissue ，and decreased the contents of inflammatory factors TNF-α，IL-1β，IL-6 and IL- 17 in hippocampus of cerebral tissue. CONCLUSIONS ：The active components of H. rhamnoides can regulate multiple targets in the important pathway of AD ；animal experiments preliminarily verify that H. rhamnoides can relieve the hippocampus injury and improve the learning and memory ability of AD model mice by inhibiting the expression of inflammatory factors.
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Objective@#To observe the short-term changes of Body Mass Index (BMI) and Waist Circumference (WC) in junior high school students in Harbin, and to explore its association with the changes of high-sensitivity C-reactive protein (hs-CRP) in the same period. Furthermore, to analyze the value of hs-CRP to predict the BMI and WC changes in children and adolescents.@*Methods@#Convenient sampling method was used,and the students in grades 6 and 7 in junior high school in Harbin were selected by stratified clicstering. Physical examination and serum hs-CRP were performed for two consecutive years. According to the results of the two surveys, the subjects were divided into control group (normal → normal), case group (abnormal → abnormal), improved group (abnormal → normal) and progression group (normal → abnormal). The multinomial logistic regression was used to analyze the predictive value of hs-CRP changes for BMI and WC changes.@*Results@#The rate of overweight and obesity among samples from junior high school was 30.6%. The increment of BMI in female was more obvious than that in male(U=17 358.0，P<0.05). Both increments in BMI and WC were positively correlated with increments in hs-CRP(P<0.05). The risk of occurrence of "BMI always abnormal" and "WC always abnormal" increased sequentially in hs-CRP "normal → abnormal", "abnormal → normal" and "abnormal → abnormal", were 3.45 times, 5.98 times and 38.84 times of "BMI is always normal", respectively; and were 3.45 times, 4.26 times and 28.50 times of "WC is always normal", respectively. The risk of "BMI improvement" was 7.70 times more than that of BMI "always normal" when hs-CRP "abnormal → normal".@*Conclusion@#The prevalence of overweight and obesity in junior high school students in Harbin is high. The BMI increases faster in female from junior high school. The trends of change of BMI and WC are consistent with the trend of change of hs-CRP. The “hs-CRP change” has a good predictive value for BMI and WC development.
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Objective@#To evaluate the role of heme oxygenase-1 (HO-1) on lipopolysaccharide (LPS)-induced activation of NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasomes in alveolar macrophages of rats.@*Methods@#NR8383 cells of rat alveolar macrophages cultured in vitro were seeded in 96-well plates at a density of 4×104 cells/ml and divided into 4 groups (n=48 each) using a random number table method: control group (group C), group LPS (group L), LPS+ HO-1 siRNA group (group L+ HO-1 siRNA), and LPS+ Con siRNA group (group L+ Con siRNA). The cells were cultured in normal culture atmosphere in group C. NR8383 cells were stimulated with 10 μg/ml LPS in L, L+ HO-1 siRNA and L+ Con siRNA groups.Cells were transfected with HO-1 siRNA at 48 h before stimulation with LPS in group L+ HO-1 siRNA and with Con siRNA at 48 h before stimulation with LPS in group L+ Con siRNA.The cells were collected and incubated for 24 h after stimulation with LPS for measurement of the cell viability, expression of HO-1 and NLRP3 mRNA (by real-time polymerase chain reaction), expression of HO-1, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1 (by Western blot), and concentrations of interleukin-1beta (IL-1β) and interleukin-18 (IL-18) in the supernatant (by enzyme-linked immunosorbent assay).@*Results@#Compared with group C, the cell viability was significantly decreased, the expression of HO-1 and NLRP3 protein and mRNA, ASC and caspase-1 was up-regulated, and the IL-1β and IL-18 concentrations were increased in L, L+ HO-1 siRNA and L+ Con siRNA groups (P<0.05). Compared with group L, the cell viability was significantly decreased, the expression of HO-1 protein and mRNA was down-regulated, and the expression of NLRP3 protein and mRNA, ASC and caspase-1 was up-regulated, and the IL-1β and IL-18 concentrations were increased in group L+ HO-1 siRNA (P<0.05), and no significant change was found in the parameters mentioned above in group L+ Con siRNA (P>0.05).@*Conclusion@#HO-1 is involved in LPS-induced activation of NLRP3 inflammasomes in alveolar macrophages of rats.
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Objective@#To analyze and explore the clinical characteristics and prognosis of patients with "double hit" multiple myeloma (MM) .@*Methods@#We retrospectively analyzed 89 MM patients in our department of Shanghai Changzheng Hospital from 2010-2016. All patients were assayed by fluorescence in situ hybridization (FISH) and TP53 gene sequencing, based on Dr. Walker BA proposed the "double hit" MM concept, and then the clinical features and prognosis were evaluated.@*Results@#In the results, 15 (16.85%) cases harbored "double hit" showed the median PFS of 8.4 months and the median OS 22.2 months, which was significantly lower than non-"double hit" patients with median PFS 14.2 months and the median OS 39.2 months, respectively (P<0.05) . Multivariate analysis displayed that the "double hit" was an independent poor prognostic factor on PFS (HR=2.171, 95%CI 1.206-3.907, P=0.010) and OS (HR=4.106, 95%CI 2.116-7.969, P<0.001) . Moreover, "double hit" MM patients had the higher adverse prognosis risk, which showed the shorter median OS and PFS than stage III of R-ISS patients (PFS 8.4 vs 11.8 months; OS 22.2 vs 24.3 months, P<0.05, respectively) .@*Conclusion@#Patients with "double hit" MM have a very poor clinical prognosis. Prospective clinical studies are urgently needed to improve these extra high risk patients.
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Objective@#To evaluate the effect of dexmedetomidine on mitochondrial dynamics in mice with endotoxin-induced acute lung injury (ALI).@*Methods@#Thirty clean-grade healthy adult male C57BL/6 mice, weighing 20-25 g, aged 2 months, were divided into 3 groups (n=10 each) using a random number table method: control group (group C), endotoxin-induced ALI group (group LPS) and endotoxin-induced ALI plus dexmedetomidine group (group LPS+ DEX). In LPS and LPS+ DEX groups, lipopolysaccharide (LPS) 10 mg/kg was injected via the caudal vein to establish the model of endotoxin-induced ALI.In group LPS+ DEX, dexmedetomidine 50 μg/kg was intraperitoneally injected at 30 min before injection of LPS, while the equal volume of normal saline was given instead in C and LPS groups.The mice were sacrificed at 6 h after LPS administration, and lung tissues were obtained for examination of the pathological changes (with a light microscope) which were scored and for determination of the level of reactive oxygen species (ROS) and expression of mitochondrial fusion proteins mitofusin 1 (Mfn1), Mfn2, optic atrophy 1 (OPA1), dynamin-related protein 1 (Drp1) and fission protein 1 (Fis1)(using Western blot).@*Results@#Compared with group C, the lung injury scores and ROS level in lung tissues were significantly increased, the expression of Mfn1, Mfn2 and OPA1 was down-regulated, and the expression of Drp1 and Fis1 was up-regulated in LPS and LPS+ DEX groups (P<0.05). Compared with group LPS, the lung injury scores and ROS level in lung tissues were significantly decreased, the expression of Mfn1, Mfn2 and OPA1 was up-regulated, and the expression of Drp1 and Fis1 was down-regulated in group LPS+ DEX (P<0.05).@*Conclusion@#Dexmedetomidine can reduce endotoxin-induced ALI through maintaining the mitochondrial fusion-fission balance in mice.