Grape Seed Extract Attenuates Demyelination in Experimental Autoimmune Encephalomyelitis Mice by Inhibiting Inflammatory Response of Immune Cells / 中国结合医学杂志

OBJECTIVE@#To examine the anti-inflammatory effect of grape seed extract (GSE) in animal and cellular models and explore its mechanism of action.@*METHODS@#This study determined the inhibitory effect of GSE on macrophage inflammation and Th1 and Th17 polarization in vitro. Based on the in vitro results, the effects and mechanisms of GSE on multiple sclerosis (MS)-experimental autoimmune encephalomyelitis (EAE) mice model were further explored. The C57BL/6 mice were intragastrically administered with 50 mg/kg of GSE once a day from the 3rd day to the 27th day after immunization. The activation of microglia, the polarization of Th1 and Th17 and the inflammatory factors such as tumor necrosis factor- α (TNF- α), interleukin-1 β (IL-1 β), IL-6, IL-12, IL-17 and interferon-γ (IFN-γ) secreted by them were detected in vitro and in vivo by flow cytometry, enzyme linked immunosorbent assay (ELISA), immunofluorescence staining and Western blot, respectively.@*RESULTS@#GSE reduced the secretion of TNF-α, IL-1 β and IL-6 in bone marrow-derived macrophages stimulated by lipopolysaccharide (P<0.01), inhibited the secretion of TNF-α, IL-1 β, IL-6, IL-12, IL-17 and IFN-γ in spleen cells of EAE mice immunized for 9 days (P<0.05 or P<0.01), and reduced the differentiation of Th1 and Th17 mediated by CD3 and CD28 factors (P<0.01). GSE significantly improved the clinical symptoms of EAE mice, and inhibited spinal cord demyelination and inflammatory cell infiltration. Peripherally, GSE downregulated the expression of toll-like-receptor 4 (TLR4) and Rho-associated kinase (ROCKII, P<0.05 or P<0.01), and inhibited the secretion of inflammatory factors (P<0.01 or P<0.05). In the central nervous system, GSE inhibited the infiltration of CD45+CD11b+ and CD45+CD4+ cells, and weakened the differentiation of Th1 and Th17 (P<0.05). Moreover, it reduced the secretion of inflammatory factors (P<0.01), and prevented the activation of microglia (P<0.05).@*CONCLUSION@#GSE had a beneficial effect on the pathogenesis and progression of EAE by inhibiting inflammatory response as a potential drug and strategy for the treatment of MS.

Clinical application and research progress of angle Kappa in ophthalmic surgery / 国际眼科杂志(Guoji Yanke Zazhi)

The human eye has various axes and angles, of which the angle Kappa is an important indicator of the centrality of the human eye and is widely used in ophthalmic surgery. Proper preoperative evaluation and application of the angle Kappa facilitated the achievement of optimal postoperative visual quality. Chord mu is a new term that has emerged recently to better express the angle Kappa. The two concepts are not well understood clinically, limiting their usefulness. Therefore, to better understand the angle Kappa and chord mu, the definitions and connections between them are presented separately in this paper. Meanwhile, the application of angle Kappa in strabismus surgery was summarized, the method for compensating large angle Kappa in corneal refractive surgery and the clinical significance of angle Kappa in predicting postoperative centrality of multifocal intraocular lens(MIOL)in phacoemulsification combined with MIOL implantation were discussed, with a view to providing references for clinical work.

Chronic psychological stress exacerbates aortic medial calcification via glucocorticoids / 生理学报

Chronic psychological stress can promote vascular diseases, such as hypertension and atherosclerosis. This study aims to explore the effects and mechanism of chronic psychological stress on aortic medial calcification (AMC). Rat arterial calcification model was established by nicotine gavage in combination with vitamin D3 (VitD3) intramuscular injection, and rat model of chronic psychological stress was induced by humid environment. Aortic calcification in rats was evaluated by using Alizarin red staining, aortic calcium content detection, and alkaline phosphatase (ALP) activity assay. The expression levels of the related proteins, including vascular smooth muscle cells (VSMCs) contractile phenotype marker SM22α, osteoblast-like phenotype marker RUNX2, and endoplasmic reticulum stress (ERS) markers (GRP78 and CHOP), were determined by Western blot. The results showed that chronic psychological stress alone induced AMC in rats, further aggravated AMC induced by nicotine in combination with VitD3, promoted the osteoblast-like phenotype transformation of VSMCs and aortic ERS activation, and significantly increased the plasma cortisol levels. The 11β-hydroxylase inhibitor metyrapone effectively reduced chronic psychological stress-induced plasma cortisol levels and ameliorated AMC and aortic ERS in chronic psychological stress model rats. Conversely, the glucocorticoid receptor agonist dexamethasone induced AMC, promoted AMC induced by nicotine combined with VitD3, and further activated aortic ERS. The above effects of dexamethasone could be inhibited by ERS inhibitor 4-phenylbutyrate. These results suggest that chronic psychological stress can lead to the occurrence and development of AMC by promoting glucocorticoid synthesis, which may provide new strategies and targets for the prevention and control of AMC.

Clinical Significance of sFLC/MP Level and Light Chain Escape in Patients with Multiple Myeloma Relapse / 中国实验血液学杂志

OBJECTIVE@#To explore the effects of serum free light chain (sFLC) and monoclonal protein (MP) on the efficacy and prognosis of patients with multiple myeloma relapse, and investigate the clinical value of light chain escape (LCE).@*METHODS@#The relationship between sFLC/MP levels and clinical features and outcomes in 71 patients with multiple myeloma after relapse were retrospective analyzed. The patients were divided into MO group, MLC group and LCE group according to different levels of sFLC/MP after relapse. Then the clinical indicators, efficacy, survival after relapse (SAR) and overall survival (OS) of the patients in each group were compared. Meanwhile a paired sample t test was used to analyze the relevant indicators of the patients before and after relapse in LCE group.@*RESULTS@#There were significant differences in ISS stage, the levels of Hb, PLT, ALB, SFLC/MP and the proportion of myeloplasma cells afte relapse (P<0.05). The initial treatment effect of the patients in MO group was better than those in the other groups, and the LCE group was the worst (P<0.05). Comparison of relevant indicators between the patients before and after relapse in LCE group showed that the levels of MP, Hb and PLT decreased significantly, while sFLC, LDH and Cr increased significantly (P<0.05). Multivariate analysis showed that MO was the independent risk factor affecting SAR, while MO and LCE were the independent risk factors affecting OS (P<0.05) of the patients.The average SAR of the patients in MO, MLC and LCE group was 41, 28.6 and 23.5 months (P=0.002), and the average OS was 79.6, 57.9 and 41 months (P<0.001), respectively. The patients in MO group showed longer SAR and OS, while the LCE group was the shortest.@*CONCLUSION@#After relapse, patients only with elevated MP levels have a better curative effect and prognosis, while only with elevated sFLC levels have poor curative effects and prognosis, which suggesting that sFLC/MP levels can be used as a good indicator for predicting the prognosis of multiple myeloma patients.The appearance of LCE indicates disease progression, poor prognosis and early relapse.

The Influence of CONUT Score on the Prognosis of Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To explore the influence of controlling nutritional status (CONUT) score on the prognosis of newly diagnosed patients with multiple myeloma (MM).@*METHODS@#The clinical data 119 patients with MM who were diagnosed according to the international myeloma diagnostic criteria in Lanzhou University Second Hospital from April 2010 to October 2018 were collected and retrospectively analyzed. The relationship between clinical indexes, including age, sex, MM type, absolute lymphocyte count (ALC), absolute neutrophil count (ANC), absolute monocyte count (AMC), hemoglobin (Hb), platelet (PLT), β@*RESULTS@#Compared with high-scoring group, low-scoring group had a better OS ［median OS was 43.3 months and 127.67 months, respectively, 95% confidence interval (CI): 57.065-78.345, P=0.038］. At the same time, the low-scoring group also had higher level of ALC, ANC, AMC, Hb, PLT, ALB, and CHO but lower of GLO. Multivariate survival analysis showed that age (HR=1.027, 95%CI: 1.000-1.054, P=0.048), AMC (HR=11.284, 95%CI: 22.968-42.897, P<0.001), CONUT score (HR=1.198, 95%CI: 1.036-1.385, P=0.015), M protein (non-IgG/IgG type) type (HR=0.503, 95%CI: 0.259-0.977, P=0.043) were independent factors affecting the prognosis of MM patients.@*CONCLUSION@#The CONUT score as an immune-nutrition score is a convenient and easy-to-obtain index to effectively predict the prognosis of MM patients.

Value of Red Blood Cell Distribution Width and Fibrinogen Level for Evaluation of the Therapeutic Efficacy and Prognosis in Patients with Diffuse Large B-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the value of red blood cell distribution width (RDW) and fibrinogen (Fib) level for the evaluation of therapeutic efficacy and prognosis in patients with diffuse large B-cell lymphoma (DLBCL).@*METHODS@#The relationship between RDW/Fib at initial diagnosis and efficacy and the clinical outcome was retro-spectively analyzed based on the study of 105 patients with DLBCL. The patients were divided into two groups: low RDW group (≤15%) and high RDW group (>15%), low Fib group (Fib≤4 g/L) and high Fib group (Fib>4 g/L) according to the normal values of RDW and Fib. Therapeutic efficacy, overall survival (OS) time and progression free survival (PFS) time were compared between two groups. The correlation between each factors and efficacy, prognosis was analyzed by univariate and multivariate regression.@*RESULTS@#The therapeutic efficacy (P<0.001), OS time(P=0.004), and PFS time(P=0.007) were poorer in the high RDW group as compared with the low RDW group. The efficacy (P=0.015) and PFS time(P=0.04) were poorer in the high Fib group as compared with the low Fib group. Multivariate analysis showed that high RDW was the independent risk factor for efficacy of DLBCL patients (OR=3.394, 95% CI 1.093-10.539, P=0.035).@*CONCLUSION@#High RDW and high Fib associate with poor efficacy in DLBCL patients.

Sucrose reward promotes rats' motivation for cocaine / 生理学报

Caloric diet, such as fat and sugar intake, has rewarding effects, and has been indicated to affect the responses to addictive substances in animal experiments. However, the possible association between sucrose reward and the motivation for addictive drugs remains to be elucidated. Thus, we carried out behavioral tests after sucrose self-administration training to determine the effects of sucrose experience on rats' motivation for cocaine, locomotor sensitivity to cocaine, basal locomotor activity, anxiety level, and associative learning ability. The sucrose-experienced (sucrose) group exhibited higher lever press, cocaine infusion and break point, as well as upshift of cocaine dose-response curve in cocaine self-administration test, as compared with the control (chow) group. Additionally, despite similar locomotor activity in open field test and comparable score in cocaine-induced conditioned place preference, the sucrose group showed higher cocaine-induced locomotor sensitivity as compared with the chow group. The anxiety level and the performance in vocal-cue induced fear memory were similar between these two groups in elevated plus maze and fear conditioning tests, respectively. Taken together, our work indicates that sucrose experience promotes the rats' motivation for cocaine.

Study on long-term toxicity of extracts from Kuntai Capsule on rats / 中草药

Objective: To observe the property and degree of long-term toxicity of Kuntai and evaluate whether the toxic injure can be prevented or recovered, so as to provide the reference for clinical safe use. Methods: One handred and twenty rats were randomly divided into four groups, Kuntai (25.0, 12.5, and 5.0 g/kg) groups and control (ig same volume of distilled water) group for all being treated for 180 d, respectively. Then the rats were sacrificed 2/3 (n = 20) in each group and the anatomy and pathological biochemical detection were carried on. And the remainings (n = 10) were sacrificed after 30 d of withdrawal drug to use for the reversible experiment. Results: There is no significance of the extract from Kuntai Capsule on the growth/hematopoietic function/biochemical criterion of serum or the pathological feature, i. e. toxicity changes with obvious injury in heart, liver, spleen, lung, kidney, uterus, ovaries, testes, the pituitary gland, and brain. Conclusion: There is very low toxicity of the extract from Kuntai Capsule for the long-term safe use which is benefit in clinic.

Involvement of Nuclear Factor Kappa B in High-Fat Diet-Related Pancreatic Fibrosis in Rats

BACKGROUND/AIMS: High-fat diets contribute to pancreatic fibrogenesis, but the pathogenesis remains unclear. This study investigated the role of nuclear factor kappa B (NF-kappaB) in high-fat diet-induced pancreatic fibrosis in rats. METHODS: Male Wistar rats were fed a high-fat diet or standard normal chow for 20 weeks. Pancreatic fibrosis was determined by Sirius red staining. Immunohistochemical staining, reverse transcription-polymerase chain reaction and Western blotting were used to identify NF-kappaB-associated genes or protein expressions. RESULTS: Inflammation, fat deposition, pancreatic stellate cell activation and fibrosis were observed in the pancreases of the high-fat diet group. NF-kappaB subunit p65 (NF-kappaB/p65) expression was localized to the nucleus, and intercellular adhesion molecule 1 (ICAM-1) was over-expressed. Pancreatic gene expression levels of NF-kappaB/p65, ICAM-1 and tumor necrosis factor alpha were all elevated significantly in rats fed a high-fat diet compared with control rats. Western blotting also revealed significantly increased levels of ICAM-1 and nuclear NF-kappaB/p65 in rats fed high-fat diets comparison with control rats. CONCLUSIONS: NF-kappaB is involved in high-fat diet-related pancreatic fibrosis.

Infection during transgastric and transvaginal natural orifice transluminal endoscopic surgery in a live porcine model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The infection risk of natural orifice transluminal endoscopic surgery (NOTES) is of concern. The aim of this study was to assess the safety of NOTES by investigating the intraperitoneal bacterial load during transgastric and transvaginal procedures with antiseptic or controlling perioperative preparation.</p><p><b>METHODS</b>Forty-five female pigs were randomly assigned to five equal groups: the transgastric (TG) control group (group A), the TG middle volume gastric lavage group (group B), the TG high volume lavage group (group C), the transvaginal (TV) control group (group D) and the TV study group (group E). The study groups received gastric or vaginal lavage and abdominal antimicrobial irrigation, while the control groups received neither. All animals were administered intravenous antibiotics, underwent NOTES peritoneoscopy and transumbilical laparoscopic cholecystectomy under NOTES view with sterile instruments. The viscerotomy was closed by laparoscopic suture. The animals were observed until necropsy was performed 14 days postoperatively. Quantitative bacteriologic cultures were taken from the gastric or vaginal aspirate before and after lavage; peritoneal fluid was collected before and after peritoneal irrigation and at necropsy.</p><p><b>RESULTS</b>The surgical procedures were completed for all the pigs and all of them survived. The mean operative time of the TG group and the TV group was (81 ± 27) minutes and (66 ± 12) minutes, respectively. All animals survived for 14 days. At necropsy, significantly more peritoneal infections were noted in group A than in group D (5:9 vs. 0:9; P < 0.05). No gross evidence of intra-peritoneal infection was found in groups B, C, D and E. Bacteriological evidence was seen in all pigs in group A, 7 pigs in group B, 6 pigs in group D, and none in groups C and E.</p><p><b>CONCLUSIONS</b>Without gastric or vaginal lavage and antibiotic peritoneal irrigation, the TG procedure has a higher infection rate than the TV access. After antiseptic preparation, the bacterial load significantly decreased in the TG group, which seems as safe as the sterile TV approach.</p>

Comparison of the Golgi proteome of hepatocellular carcinoma with that of the adjacent non-tumor tissues / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To compare the Golgi proteome of hepatocellular carcinoma (HCC) with that of the adjacent non-tumor tissues.</p><p><b>METHODS</b>Hepatocellular carcinoma and adjacent non-tumor tissues were obtained from HCC patients. The protein expression maps in Golgi were obtained by two-dimensional gel electrophoresis (2-DE), and the differentially expressed protein spots were analyzed by PD-Quest software. Peptide mass fingerprint (PMF) of differential protein spots was obtained with MALD-TOT-MS.</p><p><b>RESULTS</b>According to 2-DE maps, the average numbers of protein spots were (1153+/-49) and (1086+/-37) in hepatocellular carcinoma and the adjacent non-tumor tissues. Compared to the adjacent non-tumor tissues, 27 proteins were upregulated, and 20 proteins were downregulated in HCC Golgi.</p><p><b>CONCLUSIONS</b>The Golgi proteome in HCC tissues is different from that in the adjacent non-tumor tissues, and the differential expression proteins are involved in energy metabolism, tumor metastasis, and cell cycle regulation.</p>

Modulation of NRF2 and UGT1A expression by epigallocatechin-3-gallate in colon cancer cells and BALB/c mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Green tea is an important source of flavonoids in human diets and epidemiological data correlate green tea consumption with a reduced cancer risk. Given its complicated properties at effective concentrations, we put epigallocatechin-3-gallate (EGCG) that previously reported on its anti-proliferative activities against several cancer cell lines on our research agenda to further examine the mechanism of its chemopreventive potential.</p><p><b>METHODS</b>RNA interference (RNAi) expression vector pSilencer 3.1-H1 was used to construct recombinant nuclear factor erythroid 2 related factor 2 (Nrf2)-targeting RNAi plasmids. EGCG (5 microg/ml) was added into the culture fluid of cells before and after transfection. RT-PCR and Western blotting were used to detect the expression of uridine 5'-diphosphate-glucuronosyltransferase (UGT) 1A in cells. Forty male BALB/c mice were assigned to four groups: a normal unexposed control and three groups treated with varying doses of EGCG. Four weeks later, the mice were sacrificed, and their colon tissues were subjected to mRNA and protein expression of Nrf2 and UGT1A via RT-PCR and Western blotting analysis.</p><p><b>RESULTS</b>EGCG up-regulated the expression of Nrf2 and increased the level of UGT1A in cells. The blockade of Nrf2 activity via RNA intervention largely attenuated the induction of UGT1A expression by EGCG. In mice, the mRNA and protein levels of Nrf2 and UGT1A detected by RT-PCR and Western blotting increased (both P < 0.05 compared with the control). This increase in Nrf2 expression also had a positive correlation with an increased UGT1A expression.</p><p><b>CONCLUSIONS</b>EGCG mediated its effect in part by inducing the NRF2 signaling pathway and increasing UGT1A expression. Both in vitro and in vivo studies demonstrated the role of NRF2 and UGT1A expression in the potential use of EGCG as a possible chemopreventive agent and supported further study of EGCG for cancer treatment.</p>

Therapeutic effect of acupuncture on postoperative recovery of prolapse of lumbar intervertebral disc / 中国针灸

<p><b>OBJECTIVE</b>To evaluate therapeutic effect of comprehensive therapy of acupuncture as main in postoperative recovery of prolapse of lumbar intervertebral disc.</p><p><b>METHODS</b>Seventy-seven cases were randomly divided into an observation group (n = 40) and a control group (n = 37). The observation group were treated with acupuncture at Shenshu (BL 23), Dachangshu (BL 25), Baliao (BL 31, BL32, BL33, BL 34), Zhibian (BL 54) combined with polarized light, and the control group with western medicine dikeleke 75 mg, once daily. They were treated for 1 month.</p><p><b>RESULTS</b>The cure-markedly effective rate was 95.0% in the observation group and 75.7% in the control group with a significant difference between the two groups (P<0.05). The average VAS score was 2.28 +/- 0. 96 in the observation group and 3.49 +/- 1.45 in the control group with a significant difference between the two groups (P <0.01).</p><p><b>CONCLUSION</b>The comprehensive therapy of acupuncture as main can obviously increase the therapeutic effect in the postoperative recovery of prolapse of lumbar intervertebral disc.</p>

The role of Treg/CD4~+ T in the pathogenesis and prevention of bowel dysfunction after acute enteritis in rots / 中华消化杂志

Objective To investigate the role of Treg/CD4~+ T in the pathogenesis and prevention of bowel dysfunction after acute enteritis in rats.Methods Studies were conducted in 40 female Wistar rats with weights of 170-180 g.The rats were divided into normal control,experimental control,antibi- otics-treated,probiotics-treated and combined treated groups.The latter 4 groups were first infected with shigella flexneri by garage to establish the model of acute infectious enteritis,then normal control and experimental control group were administered 1 ml saline once everyday for 10 days.Antibiotics- treated group was given gentamycin 1 ml (8.32 mg?kg~(-)?d~(-1)) for 3 days,then was given saline 1 ml once everyday for 7 days.Probiotics-treated group was given medilac-S 1 ml (52 mg?kg~(-1)?d~(-1)) by gavage for the first 7 days,and 1 ml saline for the latter 3 days.The combined treatment group was given gentamycin for the first 3 days and medilac-S for the latter 7 days using the same dose.All rats were given colon-rectal balloon distention 16 to 22 days after the occurrence of bowel inflammation.The contraction of enteric smooth muscle was measured in vitro,the proportion of Treg cells in blood and mesenteric lymph node were analyzed by flow cytometry,and the histological changes were also observed at the same time.Statistical analyses were performed by using t test or one way ANOVA. Results No obvious changes of distal colon were histological observed in different groups.The perceptual threshold of rat gut decreased and the tension integral of enteric smooth muscle increased,and the ratio of Treg/CD4~+ T in blood and mesenteric lymph node was significantly lower in experimental control group [(4.40?0.43)%;(2.47?1.36)%] than normal controls [(5.15?0.47)%;(4.01?1.12)%,P＜0.05],while that of combined treatment group had no difference from normal controls [(4.95+0.41)%;(3.22?1.86)%].Conclusions The ratio of Treg/CD4~+ T may play an impor- tant role in the pathogenesis of post-infectious bowel dysfunction in animals.Treating acute enteritis with both antibiotics and probiotics can normalize the abnormalities,and thus prevent the occurrence of bowel dysfunction.

Clinical study of tegaserod in treatment of chronic constipation,dyspepsia and reflux overlapping symptoms / 中华消化杂志

Objective To evaluate the efficacy of tegaserod in treating overlapping symptoms of chronic constipation and dyspepsia or reflux.Methods Eighty eight patients with overlapping symptom were enrolled and randomly divided into:tegaserod group(TEG group,received tegaserod 6 mg bid), PPI group(esomeprazole 40 mg qd)and combined group(tegaserod 6 mg bid and esomeprazole 40 mg qd).Esomeprazole was taken 30 min-prior to the meals in the morning.Each group was treated for 4 weeks.Endpoints to evaluate the clinical efficacy including complete relief rates(CRRs)of epigastric symptoms,the total scores of gastrointestinal symptoms,gastric emptying and colonic transit time and gastric sensation.Results The total scores of gastrointestinal symptoms were all significantly decreased in three groups after four-week therapy,which were more decreased markedly in TEG group(7.23?3.13)and the combined group(5.13?2.26)than that in PPI group(13.58?2.02,P