OBJECTIVES: To evaluate the protective effect of Schistosoma japonicum cystatin (rSj-Cystatin) in a mouse mode of "two-hit" sepsis. METHODS: Sixty male C57BL/6 mice randomized equally into sham-operated group, protein group, "two-hit" modeling group, and protein intervention group. In the former two groups, the mice received an intraperitoneal injection of 100 μL PBS followed by exposure of the cecum and then by intraperitoneal injection of 100 μL PBS or 25 μg rSj-Cystatin 30 min later; In the latter two groups, 100 μL PBS containing LPS (5 mg/kg) was injected intraperitoneally 24 h before cecal ligation and puncture (CLP), and 100 μL PBS or 25 μg rSj-Cystatin were injected 30 min after CLP. At 12 h after rSj-Cystatin treatment, 6 mice from each group were sacrificed for detection of TNF-α, IL-6, IL-10, TGF-β, iNOS and Arg-1 in the serum, spleen, liver, lung and kidney tissues using ELISA, for examinations of liver, lung and kidney pathologies with HE staining, and for analysis of CD3⁺CD4⁺CD25⁺Foxp3⁺ T cell percentage in the spleen using flow cytometry. The remaining mice were observed for general condition and 72-h survival. RESULTS: The 72-h survival rates in the 4 groups were 100%, 100%, 0% and 20%, respectively, showing significant differences between the latter two groups. The mouse models of "two-hit" sepsis exhibited obvious tissue pathologies and significant elevations of TNF-α and IL-6 in both the serum and tissue homogenate, which were significantly ameliorated by rSj-Cystatin treatment. Treatment with rSj-Cystatin also increased IL-10 and TGF-β levels and spleen CD3⁺CD4⁺CD25⁺Foxp3⁺ T cell percentage. The septic mouse models also showed increased iNOS levels in all the detected tissues and a decreased Arg-1 level in the kidney, and these changes were obviously improved by rSj-Cystatin treatment. CONCLUSIONS rSj-Cystatin has a protective effect against "two-hit" sepsis in mice by regulating the inflammatory microenvironment.
Animals ; Mice ; Sepsis/drug therapy* ; Male ; Schistosoma japonicum/chemistry* ; Mice, Inbred C57BL ; Cystatins/therapeutic use* ; Interleukin-10/metabolism* ; Interleukin-6/blood* ; Tumor Necrosis Factor-alpha/blood* ; Disease Models, Animal ; Transforming Growth Factor beta/metabolism*

Arachidonic acid can be transformed into a variety of metabolites that trigger an inflammatory response through cyclooxygenase, lipoxygenase, cytochrome P450 enzymes, and other metabolic pathways. Moreover, it plays a key role in the occurrence and development of inflammatory diseases. In recent years, multi-target drugs based on the arachidonic acid metabolic pathway have become an important direction of anti-inflammatory drug research. This article summarizes the opportunities and challenges of arachidonic acid metabolic pathways as well as their interference in the development of anti-inflammatory drugs, reviews the research progress of multi-target drug design, synthesis, and anti-inflammatory activity based on the arachidonic acid metabolic pathway, and discusses the difficulties and prospects of multi-target drugs based on metabolic pathways in anti-inflammatory drug development, aiming to provide some reference and inspiration for the study of multi-target anti-inflammatory drugs based on the arachidonic acid metabolic pathway.

Nitroxide radicals are a kind of stable organic free radicals.Due to the presence of N-O·and unpaired electrons in its structure,it has many characteristics,and thus can be used as a spin marker to explore the mechanism of biological reactions;with its magnetic properties,it can be used for the development of multifunctional magnetic molecular materials and used as a polymerization inhibitor and catalyst in organic reactions.More importantly,it has a variety of biological activities such as anti-oxidation and anti-tumor,and so has attracted much attention in the research and development of new drugs.For example,the spin labeling of nitroxide radicals on anticancer drug podophyllotoxin can enhance the efficacy and reduce the toxicity,and can be easily to be absorbed by the body,thus obtaining a new anti-cancer drug 4-[4″-(2″,2″,6″,6″-tetramethyl-1″-piperidinyloxy nitroxide radical)amino]-4′-demethyl epipodophyllotoxin(GP-7).It is an effective way to seek new drugs by introducing pharmacophore to modify nitroxide radicals or it can be spin-labeled on active natural products to obtain new compounds with high efficiency and low toxicity.The research progress of derivatives and its biological activitives of nitroxide radicals are summarized,aiming to provide theoretical basis for the developing and utilizing of nitroxide radicals and searching for new drugs.

OBJECTIVE: The present study investigated how mild moxibustion treatment affects the intestinal microbiome and expression of NLRP3-related immune factors in a rat model of intestinal mucositis (IM) induced with 5-fluorouracil (5-Fu). METHODS: Forty male Sprague-Dawley rats were randomly divided into control, chemotherapy, moxibustion and probiotics groups. The IM rat model was established by intraperitoneal injection of 5-Fu. Mild moxibustion treatment and intragastric probiotic administration were provided once daily for 15 days. Tissue morphology, serum levels of inflammatory factors and the expression levels of tight junction proteins, caspase-1, gasdermin D and NLRP3 were evaluated in colon tissue, through hematoxylin and eosin staining, electron microscopy, enzyme-linked immunosorbent assay, Western blotting, quantitative real-time reverse transcription polymerase chain reaction and immunofluorescence. Gut microbiome profiling was conducted through 16S rRNA amplicon sequencing. RESULTS: Moxibustion and probiotic treatments significantly increased the expression levels of tight junction proteins, reduced cell apoptosis and the expression levels of caspase-1, gasdermin D and NLRP3; they also decreased the serum levels of tumor necrosis factor-α, interleukin (IL)-6, IL-1β and IL-18, while increasing serum levels of IL-10. Moxibustion and probiotic treatments also corrected the reduction in α-diversity and β-diversity in IM rats, greatly increased the proportion of the dominant bacterial genus Lactobacillus and reduced the abundance of the genera Roseburia and Escherichia in chemotherapy-treated rats to levels observed in healthy animals. We also found that these dominant genera were firmly correlated with the regulation of pyroptosis-associated proteins and inflammatory factors. Finally, moxibustion and probiotic treatments elicited similar effects in regulating intestinal host-microbial homeostasis and the expression of NLRP3 inflammasome-related factors. CONCLUSION Moxibustion exerts its therapeutic effect on IM by ameliorating mucosal damage and reducing inflammation. Moreover, moxibustion modulates the gut microbiota, likely via decreasing the expression levels of the NLRP3 inflammasome.

Objective To explore the effect of WeChat combined with 5A management model on the uncertainty in illness and the quality of life in patients with inflammatory bowel disease(IBD). Methods By convenience sampling, totally 64 patients with IBD hospitalized in Department of Gastroenterology, East Wing of the Second People's Hospital of Lianyungang in Jiangsu Province from April to December of 2018 were selected as research objects, and divided into the experimental group and control group, with 32 cases in each group according to their enrolling time. Both of the two groups received routine nursing care and health education, on the basis of that, the experimental group was implemented by the WeChat combined 5A nursing model. The two groups were compared in terms of the uncertainty in illness and quality of life before and after intervention. Results Finally, 31 valid samples were achieved in the experimental group and 30 in the control group. After intervention, each dimensional scores of sense of uncertainty in illness of the experimental group were lower than the control group with statistical significances(P＜0.01). After intervention, the total score of quality of life in the experimental group as well as the dimensional scores of "intestinal symptoms", "emotional symptom", and "social function" were all higher than the control group with statistical significances(P＜0.05), there was no statistical difference in the scores of "constitutional symptoms" dimension between the two groups (P＞ 0.05). Conclusions Wechat combined 5A nursing model can improve the uncertainty in illness of the IBD patients and improve their quality of life.

Objective: To explore the correlation between the parameters of the mandible and parameters of cervical vertebrae and craniofacial bone in class Ⅱ skeletal patients in Northeast China and to establish correlation equations expressing the relationship between the mandible and cervical vertebrae and craniofacial bone directly and quantitatively for the clinical diagnosis and treatment of orthodontics and orthognathics and for prediction. Methods : The mandible, cranial facial bone and cervical vertebrae of 201 children and adolescents aged 8 to 20 years were measured using digital cranial lateral tablets. All of the cases were divided into male (n=75) and female (n=126) groups using a sensitivity analysis method based on genetic algorithms to select the craniofacial bone and cervical bone with strong sensitivity to mandible parameters and to establish relevant equations. Results : Through sensitivity analysis, the parameters with the strongest correlation between the measured values of the mandible were H4 and SN, those with a strong correlation were SN-Ar, the anterior and posterior high ratio SGo/NGn, the Y axis angle and mandibular angle Ar-Go-Gn. The established equation was as follows: males: Ar-Pg=28.415+1.818×H4+0.746×SN(r2=0.056 8, P < 0.001); females: Ar-Pg=15.168+1.706×H4+0.675×SN+0.31×SN-Ar-0.29×Y axis angle (r2=0.611, P < 0.001). No significant difference was found between the predicted values obtained by the established equations and measured values (P > 0.05). Conclusion The mandibular length equation established by sensitivity analysis and genetic algorithms is statistically significant and can predict a certain degree of growth and development.

Objective To explore the diagnostic value of ESWAN in uterine fibroids by analyzing the ESWAN signal of uterine fibroid. Methods Conventional MRI and ESWAN were carried out in thirty-seven patients with uterine fibroids.The differences of ESWAN indexes between uterine fibroids and myometrium were analyzed by paired t-test.The value of ESWAN on diagnosing uterine fibroids was analyzed by receiver operating characteristic curve(ROC curve).Results The magnitude value,phase value,R2* value and T2*value of uterine fibroids were 1 661.69 ± 45.24,(0.006 7 ± 0.007 7)Hz,(26.69 ± 1.04)Hz and(34.68 ± 1.73)ms,respectively.The magnitude value,phase value,R2* value and T2* value of myometrium were 1 790.95 ± 49.04,(0.013 1 ± 0.011 8)Hz,(22.35 ± 0.84)Hz and(42.53 ± 2.16)ms.The magnitude value,phase value and T2* value of uterine fibroids were lower than those of myometrium (P=0.008,P=0.659 and P=0.002).While the R2* value of of uterine fibroids was higher than that of myometrium(P=0.001). The area under curve(AUC)of magnitude value,phase value,R2* value and T2* value were 0.604,0.553,0.666 and 0.662.Conclusion ESWAN can show the differences between uterine fibroids and myometrium ，while the ability to independently diagnose uterine fibroids was modest.

OBJECTIVE:To study the effect of Shui medicine Asarum insigne polysaccharide on glycolipid metabolism,renal function and oxidative stress in rats with experimental type 2 diabetes,and provide reference for its development and use. METH-ODS:60 SD rats were randomly divided into normal control group,model control group,positive control group (Irbesartan tab-lets,0.02 g/kg) and A. insigne polysaccharide low-dose,medium-dose,high-dose groups (calculated by crude drug as 2,4,8 g/kg),10 in each group. Except for normal control group,rats in other groups were intraperitoneally injected streptozotocin 75 mg/(kg·d)to induce model with diabetes. After modeling,rats in each administration group were intraperitoneally injected relevant medicines,and rats in normal control group and model control group were intragastrically administrated 5% carboxymet hylcellu-lose sodium solution,twice a day,for 42 d. After administration,UV spectrophotometer was used to detect the glycogen content in liver tissue. Automatic biochemical analyzer was used to detect 24 h urine output,24 h urinary protein content of rats,levels of tri-glyceride (TG),cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),high-density lipoprotein cholesterol (HDL-C), creatinine (Cr),urea nitrogen (BUN) in serum,and levels of superoxide dismutase (SOD),glutathione peroxidase (GSH-Px), catalase(CAT),superoxide dismutase(ROS),malondialdehyde(MDA)in kidney tissue. RESULTS:Compared with normal con-trol group,glycogen content in liver tissue of rats in model control group was decreased(P<0.05);24 h urine output and 24 h uri-nary protein content were increased(P<0.05);levels of TG,TC,LDL-C in serum were increased(P<0.05),and HDL-C level was decreased (P<0.05);levels of SOD,CAT,GSH-Px in kidney tissue were decreased (P<0.05),and levels of ROS,MDA were increased(P<0.05). Compared with model group,except that there were no significant differences in the improvement of uri-nary protein content,HDL-C level in serum,24 h urine out-put in A. insigne polysaccharide low-dose group,above-men-tioned indexes in each administration group were obviously im-proved (P<0.05). CONCLUSIONS:A. insigne polysaccha-ride can regulate lipid metabolic disorders,and improve renal function and antioxidant capacity of rats.

Objective:To optimize the parameters of the equation of sagittal craniofacial structures with different classes of malocclusion using genetic algorithms(GAS), and to explore the rules .Methods:A total of 240 patients with average angle malocclusion aged 8-18 years old were divided into three groups: Angle Class Ⅰ(n=79), Angle Class Ⅱ(n=76)and Angle Class Ⅲ(n=85) groups.In each group 10 cases were randomly selected as the test samples, the rest as the experimental samples.The cephalometric analysis was performed on all the patients'' cephalograms, and the results of Ba-N,Ba-A,Ba-S,S-Ptm,Ptm-A,Ba-Ar,Ar-Go,Go-PoG,Ba-PoG and N-S-Ar were analyzed by two independent samples t-test and One-Way ANOVA. The relevant influencing factors of craniofacial structures were found.The parameters of the equation was optimized to obtain the relevant equations using GAS.The predicted values of the optimized equation were compared with the measured values.Results:There were no significant differences in sex between Angle Class Ⅰ, Class Ⅱ and Class Ⅲ groups(P> 0.05);when the men and women with the same type were combined,the Ba-A,Ptm-A,Ar-Go,and Ba-PoG had statistically significant differences between Angle Class Ⅰ, Class Ⅱ, and Class Ⅲ groups (P<0.05).The correlation analysis results showed that in Angle Class Ⅰgroup:Ba-A was positively correlated with Ba-N (r=0.683),Ptm-A was positively correlated with Go-PoG (r=0.738), Ar-Go was positively correlated with Ba-PoG (r=0.833), and negatively correlated with Go-PoG (r=-0.560) and Ba-PoG was positively correlated with Go-PoG (r=0.669);in Angle class Ⅱ group,Ba-A was positively correlated with Ba-PoG and Ba-N(r=0.884,r=0.883), Ptm-A was positively correlated with Ba-A (r=0.742),Ar-Go was positively correlated with Ba-PoG (r=0.401)and negatively correlated with Go-PoG (r=-0.317) and Ba-PoG was positively correlated with Ba-A and Go-PoG(r=0.883,r=0.488);in Angle Class Ⅲ group,Ba-A was positively correlated with Ba-N and Ba-PoG(r=0.891,r=0.829),Ptm-A was positively correlated with Ba-A (r=0.807)and negatively correlated with Ba-S (r=-0.404),Ar-Go was positively correlated with S-Ptm (r=0.548) and Ba-PoG was positively correlated with Ba-A (r=0.829).The equation of sagittal craniofacial structure with different occlusal classes was established by GAS.In Angle Class Ⅰgroup:Ba-A(mm)=10.963 9+0.859 8×Ba-N,Ptm-A(mm)=6.897 6+0.557 0×Go-PoG,Ar-Go(mm)=-2.548 2+0.511 8×Ba-PoG-0.5272×Go-PoG,Ba-PoG(mm)=17.515 6+1.021 3×GO-POG;in Angle Class Ⅱ group:Ba-A(mm)=-2.121 3+0.567 6× Ba-PoG+0.513 2× Ba-N,Ptm-A(mm)=13.788 7+0.349 4×Ba-A,Ar-Go(mm)=2.447 7+0.368 8×Ba-PoG-0.427 9×Go-PoG,Ba-PoG(mm)=-7.140 2+0.751 3×Ba-A+0.295 4×Go-PoG;in Angle Class Ⅲgroup:Ba-A(mm)=3.281 0+0.545 3×Ba-N+0.394 4× Ba-PoG,Ptm-A(mm)=3.535 8+0.63 1×Ba-A-0.614 2×Ba-S,Ar-Go(mm)=-9.002 1+1.004 3×S-Ptm,Ba-PoG(mm)=-2.091 2+1.057 5×Ba-A.There were no significant differences between the predicted values of GAS and the measured data (P> 0.05), and the error was small.Conclusion: The optimal relation equation of craniofacial structure of sagittal malocclusion is established by GAS with the quantitative regularity.

Objective To investigate the safety and effectiveness of mesh and non-mesh techniques in laparoscopic repair of large hiatal hernias (LRLHH).Methods A retrospective clinical controlled study of mesh and non-mesh techniques in LRLHH form January 2006 to August 2014 was performed.Results A total of 83 and 36 patients were recruited to mesh and non-mesh group respectively.There were no significant differences in operation time,operation bleeding volume,hospitalization time or complications between the two groups.Main symptoms were significantly improved during the postoperative long-term follow-up in both groups.The improvement of dysphagia in mesh group showed no significant difference [22.9％ (19/83) VS 12.0％ (10/83),P=0.066],however,non-mesh group showed significant difference [30.6％ (11/36) VS 5.6％ (2/36),P=0.006].Rate of dysphagia alleviation in non-mesh group was significantly higher than that in mesh group [25.0％ (9/36) VS 10.8％ (9/83),P =0.048].Mesh-related complications of esophageal erosions occurred in 5 patients (6.0％) in mesh group,including esophageal stenosis in 3 patients,esophageal-cardiac stricture in 1 patient.Recurrent hernia occurred in 1 patient (1.2％) in mesh group and 3 patients (8.3％) in non-mesh group (P =0.082).Conclusion LRLHH with mesh should be individualized.The use of mesh in LRLHH reduces the recurrence rate,but may lead to some complications.