The aim of this study was to investigate the therapeutic effects and potential mechanism of c(RGDyK) peptide modified mesenchymal stem cell exosomes loaded with ginsenoside Rg1 (G-Rg1) on ischemic stroke. Thread-tying method was used to establish SD rats transient middle cerebral occlusion model (tMCAO). The model rats were randomly divided into tMCAO group, Exo group, free G-Rg1 group, Exo-Rg1 group and cRGD-Exo-Rg1 group, and sham group was used as control. The infarct volume was measured by 2, 3, 5-triphenyltetrachloride (TTC) staining, the changes of neuron and endothelium were observed by immunofluorescence, and the expression of related proteins was detected by Western blotting. The results showed that cRGD-Exo-Rg1 up-regulated the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factors (HIF-1α) by activating PI3K/AKT pathway, thus promoting angiogenesis and neurogenesis, effectively reducing the volume of cerebral infarction and improving neural function. In addition, the delivery of cRGD-Exo-Rg1 to ischemic brain tissue up-regulated the expression of occludin and claudin-5, and reduced the injury of blood-brain barrier. Taken together, cRGD-Exo-Rg1 was effective in the treatment of ischemic stroke by promoting angiogenesis and neurogenesis, which provided experimental evidence for the potential clinical benefits of other neuroprotective therapies.
Rats ; Animals ; Ischemic Stroke/drug therapy* ; Rats, Sprague-Dawley ; Phosphatidylinositol 3-Kinases ; Vascular Endothelial Growth Factor A/metabolism* ; Exosomes/metabolism* ; Ginsenosides/therapeutic use*

Objective To investigate the effects of minocycline on cell viability and neurite outgrowth of pheochromocytoma cells (PC12) after oxygen‐glucose deprivation(OGD) injury .Methods PC12 cells were exposed to OGD insult for 2 ,4 ,6 ,8 h to estab‐lish a cerebral ischemia model in vitro .High‐differentiated PC12 cells were cultivated and randomly divided into three groups :con‐trol group ,OGD group and various doses of minocycline(0 .1 ,1 .0 ,10 .0 μM) treated group .24 h after OGD‐reperfusion ,PC12 cells viability was assessed by CCK‐8 assay ,the neurite was labeled with MAP‐2 by immunofluorescence and neurite length was meas‐ured by the Image‐Pro Plus 7 .0 software ,GAP‐43 protein expression was determined by Western blotting .Results Compared to the OGD groups ,minocycline induced a concentration‐dependent increase in cells viability [(46 .1 ± 2 .9)% vs .(77 .0 ± 2 .5)% ,P<0.01],improvedneuriteoutgrowthandincreasedtheexpressionofGAP‐43proteininPC12cellsafterOGDinjury([(0.34±0.04) vs .(2 .11 ± 0 .10) ,P<0 .01] .Conclusion Minocycline could protect against oxygen glucose deprivation injury and promote neurite outgrowth .This finding suggests minocycline may be a novel therapy for cerebral ischemia .

Objective : To screen the RNA binding proteins interacting with NBV nonstructural protein σNS in host cells and to analyze their bioinformatics functions. Methods : In this study , the eukaryotic expression vector pEF⁃HA⁃MB⁃S3 of NBV σ NS was constructed and transfected into HEK293T cells after verification. After RNase A treatment , the obtained protein lysate was enriched by immunoprecipitation to enrich σNS binding proteins , identified and analyzed by LC⁃MS/MS mass spectrometry , and the properties and specific functions of proteins were discovered with the help of related Bioinformatics tools. Results : In this study , 32 candidate RNA binding proteins interacting with NBV σNS proteins were successfully screened , and the results of bioanalysis showed that these proteins were mainly located in cytoplasm and nucleus , and were mainly involved in biological processes such as cell metabolism , biological regulation , virus translation and transcription. Conclusion This study preliminarily analyzes the function of RNA binding proteins interacting with NBV σNS , which lays a foundation for further study on the mechanism of σNS protein in NBV life cycle.

Background and purpose:For stageⅠ non-small cell lung cancer (NSCLC), video-assisted thoracic segmentectomy is given much attention to by thoracic surgeon because of the less tissue damages. However, video-assisted thoracic lobectomy is still considered as the standard treatment in the world. Therefore, this study was to evaluate the clinical effect after video-assisted thoracic segmentectomy and lobectomy in patients with stageⅠ NSCLC in order to provide reference for clinical application.Methods:The comparative studies on video-assisted thoracic segmentectomy and lobectomy treating stage I NSCLC were retrieved from PubMed, Web of Science, EMBASE, the Cochrane Library, CNKI, CBM, VIP, and Wanfang Data. All data were acquired until July 2015. Literature screening according to data extraction and quality assessment was completed by two reviewers independently. Meta-analysis was conducted by RevMan 5.3 software which was offered by Cochrane network.Results:A total of 11 articles involving 1 677 patients were ifnally included. The results of meta-analysis indicated that: for stageⅠ NSCLC, compared with video-assisted thoracic lobectomy, the effect of video-assisted thoracic segmentectomy was alike in total mortality (OR=0.77, 95%CI: 0.48 to 1.21,P=0.25), 5-year mortality (OR=0.77, 95%CI: 0.52 to 1.14,P=0.19) and systemic complications (OR=0.76, 95%CI: 0.53 to 1.09,P=0.13), but could reduce blood loss [difference in means (MD)=-41.16, 95%CI: -59.46 to -22.86,P<0.000 1], chest tube duration (MD=-0.29, 95%CI: -0.49 to -0.09,P=0.005) and the length of hospital stay (MD=-0.74, 95%CI: -1.44 to -0.05,P=0.04).Conclusion:Compared with video-assisted thoracic lobectomy, video-assisted thoracic segmentectomy can signiifcantly reduce blood loss, chest tube duration and length of hospital stay. However, the two kinds of operation methods achieved the same effects on the total mortality, 5-year mortality and systemic complications. Thoracoscopic segmentectomy may be an alternative to thoracic lobectomy.

OBJECTIVE: To determine the effect of curcumin on diabetic nephropathy in db/db mice and its possible mechanism. METHODS: Ten female db/db mice were randomly divided into 2 groups: one was treated with curcumin at 200 mg/(kg.d) and the other was a placebo group. Five age-matched db/m mice were grouped as the controls. In the curcumin group, curcumin was administered to db/db mice for 18 weeks. At the end of the experiment, the blood glucose and albumin were measured, and the kidney tissue sections were stained with PAS to observe the pathological changes. The expression of collagen IV and FN in the kidney was detected by immunohitochemistry staining. Western blot was used to detect the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and IκB in the kidney. RESULTS: Compared with db/m mice, the weight and blood glucose of db/db mice were markedly increased, accompanied with heavy proteinuria, glomerulus hypertrophy, mesangial area expansion, thickening of basement membrane and ECM deposition. The phosphorylation of STAT3 was upregulated and the degradation of IκB was increased. Compared with the db/db mice, curcumin significantly decreased the urinary albumin, inhibited the phosphorylation of STAT3 and the degradation of IκB, and reduced the expression of collagen IV and FN in the kidney. CONCLUSION Curcumin can obviously decrease albuminuria and attenuate glomerular sclerosis in diabetic db/db mice by inhibiting phosphorylation of STAT3 and degradation of IκB.
Albuminuria ; Animals ; Blood Glucose ; Collagen Type IV ; metabolism ; Curcumin ; pharmacology ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; drug therapy ; Female ; Fibronectins ; metabolism ; I-kappa B Proteins ; metabolism ; Kidney ; drug effects ; metabolism ; Mice ; Phosphorylation ; Proteinuria ; STAT3 Transcription Factor ; metabolism

Animal medicine is a unique part of traditional Chinese medicine. They have strong effects, but their effective compounds are not entirely known. The efficiency and safety of animal medicines can't be effectively controlled by current quality assurance system and evaluation method, which has deeply influenced the development of animal medicines. Biological assay does not focus on efficacy of single component, but directly reflects the pharmacodynamics and safety of animal medicines by biological effect. With the development of biotechnology, many new technologies have emerged, such as biochip and high content analysis. Based on the related targets, pathways and key biochemical factors, the field of biological assay has been expanded. With advantages of pharmacology andoverall controllability, as well as the characteristics of in line with the quality control of Chinese Medicine, biological assay will become one of the important development directionsfor quality standardization of animal medicines.

In this study, the model of Propionibacterium acnes/lipopolysaccharide (P. acnes/LPS)-induced acute liver injury in mice was employed to investigate the protective effects of Fuzheng Yanggan Fomula (FYF) on acute liver injury. The effects of FYF on the contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and interleukin-1β (IL-1β) in the serum, and the levels of malondialdehyde (MDA), oxygen radical absorbance capacity (ORAC), and glutathione (GSH) were examined in the livers of mice treated with P. acnes/LPS; The protein expression levels of Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), cysteinyl aspartate specific proteinase-1 (caspase-1), and IL-1β in liver tissues were detected by Western blot; Furthermore, hematoxylinendash-eosin (HE) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and immunohistochemical assay were used to observe pathological changes, apoptosis index, and inflammation infiltration of the liver tissue sections. All animal welfare and experimental procedures were followed by the Animal Ethics Committee of Jinan University. We conclude that FYF could alleviate P. acnes/LPS induced pathological damage and inflammatory infiltration in the liver of mice. Meanwhile, FYF decreases the contents of ALT, AST, IL-1β, and MDA, increases the contents of ORAC and GSH, and downregulates the expression of caspase-1 and IL-1β proteins. Collectively, these findings suggested that FYF could alleviate P. acnes/LPS induced acute liver injury in mice by inhibiting the activation of NLRP3 inflammasome, which provides a theoretical basis and a new drug target for the prevention and treatment of liver injury.

Spinal cord injuries is an extremely serious central nervous system injury. The clinical prognosis is very poor. Patients are often associated with lifelong disabilities or paralysis. Regulating NSCs to repair spinal cord injuries is unanimously considered to be a very potential option for the treatment of this type of disease. China has a large population and a large number of patients with spinal cord injuries. Actively regulating spinal cord NSCs is of great significance for the regeneration and repair of spinal cord injuries. Endogenous NSCs avoid many disadvantages of exogenous stem cell transplantation, and have a broader prospect in the treatment of spinal cord injuries. The Wnt signaling pathway plays a very important role in the differentiation of NSCs and the development of the nervous system. However, the molecular mechanism of the proliferation and differentiation of NSCs during regeneration and repair after spinal cord injuries is still not fully understood. This article mainly describes the research progress of Wnt pathway regulating NSCs in the regeneration and repair of spinal cord injuries.

Objective To investigate the clinical efficacy of open reduction and internal fixation with K-wires for old Gartland Ⅲ supracondylar fracture in children.Methods A retrospective case series study was conducted on 49 children with old Gartland Ⅲ supracondylar humeral fracture admitted from June 2012 to January 2017.There were 35 boys and 14 girls,with average age of 6.1 years (range,3.4-11.5 years).The duration from initial trauma to operation ranged from 22 days to 60 days (mean,29.8 days).There were five cases of radial nerve injury,one case of median nerve injury,and one case of Volkmann ischemic contracture.All patients were surgically treated with open reduction and internal fixation with K-wires + plaster external fixation.Six patients with nerve injury underwent neurological exploration and release.Nerve partial fracture was seen in one patient during operation,and nerve repair was performed.The fracture healing and complications were observed.At the final follow up,Flynn's criteria was applied to evaluate the elbow joint function.The humerus length and transverse diameter of humeral condyle between the healthy limb and the suffered one were compared to evaluate the humerus growth.Results All patients were followed up for 6-24 months,with an average of 12.5 months.All fractures were healed,with no fracture redisplacement or bone nonunion occurred.The neurological symptoms of six patients with nerve injury disappeared after two months.One patient had superficial skin infection at the incision and recovered after treatment.Six patients (12％) developed cubitus varus deformity after operation.At the final follow-up,the clinical and radiographic outcomes were assessed via Flynn's criteria,and the results were excellent in 37 patients,good in five,fair in one,and poor in six patients,with an excellent and good rate of 86％.There were no significant differences in the humerus length [(189.3 ± 27.8) mm vs.(190.6 ± 28.8) mm] and transverse diameter of humeral condylar [(29.5 ± 3.5) mm vs.(29.7 ± 3.6) mm] (P ＞ 0.05) between the healthy limb and the suffered one,respectively.Conclusion For old Gartland type Ⅲ supracondylar humeral fracture in children,open reduction and internal fixation with K-wires + plaster external fixation can attain satisfactory function recovery of elbow joint and reduce the incidence of cubitus varus deformity,without negative influence on children's humerus growth or development.

Objective    To evaluate the safety and efficacy of mitral valve surgery and cryoablation in elderly patients with mitral valve disease and persistent or long-term persistent atrial fibrillation. Methods    From May 2014 to July 2018, 144 patients with mitral valve diseases combined with persistent or long-term persistent atrial fibrillation in the Department of Cardiothoracic Surgery, General Hospital of Northern Theater Command were selected. Among them, there were 69 patients in a non-elderly group (<60 years) including 18 males and 51 females aged 52.07±5.56 years, and 75 patients in an elderly group (≥60 years) including 32 males and 43 females aged 65.23±4.29 years. A propensity-score matching (PSM) study was conducted to eliminate confounding factors. Both groups underwent mitral valve surgery and cryoablation at the same time. A 2-year follow-up was conducted after discharge from the hospital, and the perioperative and postoperative efficacy indexes were compared between the two groups. Results    After PSM analysis, there were 56 patients in each group. The sinus rhythm conversion rate of the two groups at each follow-up time point was above 85%, and the cardiac function was graded asⅠorⅡ, which was significantly improved compared with that before the surgery, but there was no statistical difference between the two groups (P>0.05). Among the perioperative indicators of the two groups, the elderly group had more coronary artery bypass graft surgeries and longer postoperative ICU stay time compared with the non-elderly group (P<0.05), and the differences in other indicators were not statistically different (P>0.05). Conclusion    The mitral valve surgery and cryoablation in elderly patients with mitral valve diseases combined with persistent or long-term persistent atrial fibrillation are safe, and the short-term outcome is satisfactory.