Duhuo Jisheng Decoction treats gouty arthritis by inhibiting NLRP3 inflammasome activation / 中国组织工程研究

BACKGROUND:The activation of NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome has been found to be an important factor in the pathogenesis of gouty arthritis,and the activation of NLPR3 inflammasome can be effectively inhibited by regulating the PTEN-induced kinas 1(PINK1)/Parkin signaling pathway. OBJECTIVE:To investigate the effect of Duhuo Jisheng Decoction on the PINK1/Parkin/NLRP3 signaling pathway. METHODS:(1)Animal experiment:Male Sprague-Dawley rats were randomly divided into control group,model group,positive control group(Qiushuixian tablets 0.3 mg/kg),and low-,medium-,and high-dose Duhuo Jisheng Decoction groups(6.9,13.8,and 27.6 g/kg,respectively).A rat gouty arthritis model was constructed by injecting monosodium urate crystal suspension into the right hind ankle joint cavity of rats in all the groups except for the control group.(2)Cell experiment:Human monocytes(THP-1)were divided into blank control group,model group,Duhuo Jisheng Decoction-containing serum group,and PINK1 siRNA+Duhuo Jisheng Decoction-containing serum group.The cells in each group except the blank control group were stimulated with sodium urate to establish an in vitro gouty arthritis model.(3)The swelling degree,joint circumference,gait score,joint inflammation index and degree of pathological grading in the ankle joints of rats were observed.Enzyme-linked immunosorbent assay was used to detect the levels of uric acid,C-reactive protein,NLRP3,and interleukin 1β.Immunoblotting assay was used to detect the levels of proteins related to the PINK1/Parkin/NLRP3 pathway.Tetramethyl azolidine blue assay was used to detect cell activity.Immunofluorescent double staining was performed to detect the level of mitophagy.Immunofluorescence was used to detect the expression of NLRP3 and interleukin 1β. RESULTS AND CONCLUSION:(1)Compared with the control group,rats in the model group showed elevated ankle swelling and ankle circumference at 6-48 hours(P<0.05),elevated gait scores and joint inflammation indexes at 24 and 48 hours(P<0.05),elevated serum uric acid and C-reactive protein levels,degree of pathological classification,expression of PINK1,Parkin,and NLRP3 proteins,and interleukin 1β level in synovial tissues(P<0.05).Compared with the model group,the protein expression levels of PINK1 and Parkin in all the Duhuo Jisheng Decoction groups were elevated,while the levels of the other indexes were decreased(P<0.05).(2)Compared with the model group,NLRP3 activity,interleukin 1β level and mitochondrial outer membrane translocator protein 20 protein level in the Duhuo Jisheng Decoction-containing serum group were decreased(P<0.05),while the proliferation inhibition rate,PINK1,Parkin and LC3B protein level were increased(P<0.05).Compared with the model group,the mitochondrial autophagy level of cells in the Duhuo Jisheng Decoction-containing serum group was elevated(P<0.05),while NLRP3 and interleukin 1β protein levels were decreased(P<0.05).(3)Compared with the Duhuo Jisheng Decoction-containing serum group,the mitochondrial autophagy level of cells in the PINK1 siRNA+Duhuo Jisheng Decoction-containing serum group was decreased(P<0.05),and the expression levels of NLRP3 and interleukin 1β were elevated(P<0.05).To conclude,Duhuo Jisheng Decoction inhibits the activation of NLRP3 inflammasome by regulating the PINK1/Parkin signaling pathway, thereby exerting a therapeutic effect on gouty arthritis.

Exosomes derived from neural stem cells regulates neural stem cells and applicates in nervous system diseases / 中华神经医学杂志

In recent years, studies have shown that transplanted neural stem cells (NSCs) help neural tissues regenerate and return to normal through paracrine action rather than just replacing cells. Exosomes are essential paracrine mediators that can participate in cell communication through substance transmission. This review focuses on NSCs regulated by exosomes and their application in treatment of nervous system diseases, in order to provide important references for further research and clinical application of NSCs exosomes..

Prevalence of allergic diseases and associated factors among schoolaged children in Shanghai / 中国学校卫生

Objective@#To examine the prevalence of allergic diseases in schoolaged children from Shanghai and to explore related factors so as to produce epidemiological data regarding allergic diseases in children.@*Methods@#Multistage cluster sampling was used to carry out the study in Shanghai from April to June 2019. A total of 10 686 children aged 7-12 years from 17 primary schools participated in the survey. The International Study of Asthma and Allergies in Childhood (ISAAC)Scale was used to evaluate allergic diseases. Multivariate Logistic regression analysis was performed to analyze the related factors.@*Results@#The overall prevalence of allergic diseases among schoolaged children in Shanghai was 47.0%. A higher prevalence was observed among boys (50.4% vs 43.3% in girls, χ2=54.44, P<0.01). Common allergic diseases included asthma (13.9%), allergic rhinitis (18.2%), and atopic dermatitis (34.3%). The Logistic regression analysis showed that the common risk factors of asthma, allergic rhinitis and atopic dermatitis included the following:male gender (OR=1.52,1.44,1.22); mother has a bachelors degree or above (OR=1.26,1.77,1.84); family history of allergic diseases (OR=2.87,4.24,2.57); only child (OR=1.16,1.28,1.22); curtain cleaning frequency <1 time/month (OR=1.41,1.79,1.77); room not cleaned daily (OR=1.14,1.18,1.20); and dust exposure frequency ≥1 time/month (OR=1.45,1.56,1.42), all P<0.05. These three types of allergic diseases were also associated with unique risk factors that dependent on socialenvironmentalbehavioral factors.@*Conclusion@#Compared with previous data, the prevalence of allergic diseases among schoolaged children in Shanghai increased significantly in 2019. The related influencing factors involve multiple variables including demographics, environmental exposure and behavior, which warrant further exploration.

Efficacy analysis of radical intensity-modulated radiotherapy combined with concurrent chemotherapy for treatment of metastatic nasopharyngeal carcinoma / 肿瘤研究与临床

Objective To investigate the clinical effects of radical intensity-modulated radiotherapy (IMRT) combined with concurrent chemotherapy in the treatment of metastatic nasopharyngeal carcinoma. Methods Ninety patients with metastatic nasopharyngeal carcinoma in the First Affiliated Hospital of Hainan Medical University from August 2010 to April 2015 were selected as the research objects. All the patients were randomly divided into the observation group (45 cases) and the control group (45 cases) according to the random lottery envelope. The control group was treated with conventional chemotherapy treatment, and the observation group was treated with radical IMRT based on the treatment of the control group. The efficacy of the patients in both groups was evaluated after the treatment for 4 periods. Results The effective rate in the observation group was higher than that in the control group [66.7 % (30/45) vs. 33.3 % (15/45); χ2= 4.552, P＜ 0.05]. In the observation group, there were 3 cases of radiation esophageal injury and 3 cases of lung injury, and the incidence rate was 13.3 % (6/45), bringing the better treatment outcome. The incidence of side effects such as hair loss, nausea and vomiting, liver and kidney damage, bone marrow suppression in the observation group was 71.1 % (32/45), which was higher than that in the control group [66.7 % (30/45)] and there was no significant difference (χ 2= 0.331, P＞ 0.05). All the patients were followed up. 1 yeas and 2 year survival rates in the observation group were 95.6 % (43/45) and 86.7 % (39/45) respectively, while the control group were respectively 75.6 % (34/45) and 64.4 % (29/45) (χ2values were 6.393 and 5.309, both P＜0.05). Conclusion Radical IMRT combined with concurrent chemotherapy for metastatic nasopharyngeal carcinoma can improve the therapeutic effect and show good safety, and the radiation damage would not affect the treatment process.

Expression of high-risk HPV and ATM in human laryngeal squamous cell carcinoma and its clinical significance / 实用医学杂志

Objective To study the expression of human papillomavirus ( HPV) and ATM protein in laryngeal squamous cell carcinoma (LSCC), and discuss the correlation among the expression and its prognosis Method The expression of HPV16/18 mRNA was detected by PCR , and the expression of ATM proteins by immunohistochemical method in 63 LSCC specimens and 30 specimens of normal tissue adjacent to cancer. Results The positive expression rates of HPV16 /18 and ATM protein in LSCC group were 39.7% (25 /63) and 41. 3% (26 /63) respectively and those of HPV16 /18 and ATM protein in normal group were 9.5% ( 6/63 ) and 83.3% (25 /30) respectively. There was no correlation between the expression of ATM and HPV16/18 in LSCC. The accumulative 5-year survival rates of HPV16/18 positive group and HPV16/18 negative group in 63 patients were 69.8% and 52.6% respectively ,and there was no significant difference (P> 0.05. The accumulative 5-year survival rates of ATM positive group and ATM negative group in 63 patients were 65.4%and 45.9% respectively and there was no significant difference (P>0.05. Conclusion Both HPV16/18 and ATM are abnormally expressed in LSCC , but there is no correlation between the expression of HPV16/18 and ATM and the expression and its prognosis.

Inhibitory effect of kaempferol on inflammatory response of lipopolysaccharide-stimulated human mast cells / 药学学报

This study is to investigate the inhibitory effect of kaempferol on inflammatory response of lipopolysaccharide(LPS)-stimulated HMC-1 mast cells. The cytotoxicity of kaempferol to HMC-1 mast cells were analyzed by using MTT assay and then the administration concentrations of kaempferol were established. Histamine, IL-6, IL-8, IL-1β and TNF-α were measured using ELISA assay in activated HMC-1 mast cells after incubation with various concentrations of kaempferol (10, 20 and 40 µmol.L-1). Western blot was used to test the protein expression of p-IKKβ, IκBα, p-IκBα and nucleus NF-κB of LPS-induced HMC-1 mast cells after incubation with different concentrations of kaempferol. The optimal concentrations of kaempferol were defined as the range from 5 µmol.L-1 to 40 µmol.L-1. Kaempferol significantly decreased the release of histamine, IL-6, IL-8, IL-1β and TNF-α of activated HMC-1 mast cells (P<0.01). After incubation with kaempferol, the protein expression of p-IKKβ, p-IKBa and nucleus NF-κB (p65) markedly reduced in LPS-stimulated HMC-1 mast cells (P<0.01). Taken together, we concluded that kaempferol markedly inhibit mast cell-mediated inflammatory response. At the same time, kaempferol can inhibit the activation of IKKβ, block the phosphorylation of IκBα, prevent NF-KB entering into the nucleus, and then decrease the release of inflammatory mediators.

Analysis of inhaled allergens in the patients with chronic rhinosinusitis in Hainan province / 实用医学杂志

Objective To understand the distribution of inhaled allergens throughout Hainan province and explore effective preventive measures against allergen by examining the serum allergen of patients with chronic rhinosinusitis (CRS), which will provide evidence for specific immunotherapy for treating CRS. Methods Three hundred and eighteen CRS patients underwent Phadiatop blood test by using the UniCAP 100 , a completely automatic autoanalyser. Allergen-specific IgE of 7 common allergens were tested and the concentration of total immunoglobulin E (TIgE) was collected and evaluated. Results The positive rates of the serum TIgE and inhaled allergens were 64.15% and 37.74% respectively. The incidences of the positive serum SIgE is 33.96%. Among the positive cases, 28.30% of the inhaled allergens were dermatophagoides pteronyssinus, 27.36% for tropical mites, 21.07% for dermatophagoides farinae, 13.52% for cockroach, 11. 64% for house dust, 7. 86% for cat dander and 0.63% for dog dander. The incidences of positive TIgE and SIgE were not significantly different between patients with nasal polyps and sinusitis only. Conclusions Dermatophagoides pteronyssinus, tropical mites and dermatophagoides farinae are the main inhaled allergens for CRS patients in Hainan.

Feeling Technological Power in the Conflict of Human with SARS / 中华医学教育探索杂志

To briefly look back the fighting history of human against pestilence,we proved that human civilization was developed and perfected in the conflict with pestilence continuously.In the early 21st century,SARS,as a sort of severe acute infectious diseases,indulged in wilful persecution all over the world and brought new panic,crisis and challenges to us.However,modern technological advancement improved human power against natural disasters and plagues,and SARS was prevented and controlled in a short period.These achievements thoroughly showed power of modern technology.

Preparation of ~(99)Tc~m-ASON-EGF and its pharmacokinetic features in rabbits / 第三军医大学学报

Objective To prepare and explore the pharmacokinetic parameters for ~ 99 Tc~ m -ASON-EGF in healthy rabbits. Methods ~ 99 Tc~ m -ASON-EGF was prepared according to previous methods and its changes of concentration in blood were measured by radioactivity counts per minute. The experimental data were dealt with by 3p97 software and its true compartment model was estimated by AIC value, R~ 2 value, the 1/c and F test. Subsequently, its half-life of distribution (T_ 1/2 ?), half-life of elimination (T_ 1/2 ?), central compartment volume of distribution (Vc), total apparent volume of distribution (Vd) and total rate of clearance (CL) were calculated by the software. Finally, the binding rate of plasma protein was determined by trichloroacetic acid precipitation. Results The best model of ~ 99 Tc~ m -ASON-EGF in vivo was two-compartment model and its T_ 1/2 ?, T_ 1/2 ?, Vc, Vd and CL were 5.28 min, 89.23 min, 67.8 ml, 915.6 ml and 7.1 ml/min respectively. After being incubated with fresh plasma for 1.5 h, its binding rate was 10.69%. Conclusion Its process of transportation in healthy rabbits is fitted to two-compartment model and the pharmacokinetic properties are desirable.

Preparation of ~(99m) Tc-MAG_3-ASON and distribution in breast carcinoma-bearing nude mouse model / 重庆医科大学学报

Objective:To discuss the preparation of ~(99m) Tc-labelled antisense oligonucleotide (ASON) and its distribution in breast carcinoma-bearing nude mouse model.Methods:N-hydroxysuccinimide ester of mercaptoacetylglycylglycylglycine (NHS-MAG_3) was synthesized by one step.A 15-mer single-stranded phosphorothioate ASON complementary to c-erbB2 oncogene mRNA was coupled with NHS-MAG_3 and labelled with ~(99m) Tc subsequently.~(99m)Tc-MAG_3-ASON was purified on a gel filtration column of Sephadex G25,then its stability was evaluated,and finally the distribution was detected in breast carcinoma-bearing nude mice model.Results: The average labeling efficiency of 99mTc-MAG_3-ASON was 70.6%,and the radiochemical purity was 94.3% after being labelled at room temperature for 4h. When incubated with fresh human serum, the radiochemical purity of ~(99m) Tc-MAG_3-ASON was 93.8%. The serum protein binding of ~(99m) Tc-MAG_3-ASON was 11.8%.The highest uptake of breast carcinoma was 6.09%ID/g at 2hs.Conclusion:~(99m)Tc-MAG_3-ASON has desirable stability,higher uptake in breast carcinoma and may provide a new sensitive tool for diagnostic imaging and therapy for breast carcinoma in the future.

Study of Pharmacokinetic Properties for ~(99m)Tc-MAG_3-ASON / 重庆医科大学学报

Objective: To study the pharmacokinetic properties of 99mTc-labeled chelic polymer of MAG3-ASON.Methods: Chelic polymer of 99mTc-MAG3-ASON was prepared according to former methods.Subsequently,this chelic polymer change of concentration was determined by radioactivity counts per minute(CPM),and its half-life of distribution(T1/2?),the half-life of elimination(T1/2?),the central compartment volume of distribution(Vc),the total apparent volume of distribution(Vd) and the total rate of clearance(CL) were calculated by means of 3P97 software.Finally,its rate of binding to serum protein was measured by trichloroacetic acid precipitation.Results: The T1/2?,the T1/2?,the Vc,the Vd and the CL were 2.11min,95.19min,114.9ml,2430.8ml and 17.7ml/min,respectively.After being incubated with fresh human serum for 1.5h,its rate of binding to serum protein was 11.82%.Conclusion: The process of transportation for chelic polymer of 99mTc-MAG3-ASON in vivo is consistent with two-compartment model and it has desirable pharmacokinetic properties.Therefore,it may be used for diagnostic imaging and therapy of cancer.