Mechanism of total flavonoids of Ziziphora clinopodioides in improving atherosclerosis by regulating PI3K/Akt/mTOR pathway / 中国中药杂志

The present study observed the regulatory effect of total flavonoids of Ziziphora clinopodioides on autophagy and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathways in ApoE~(-/-) mice and explored the mechanism of total flavonoids of Z. clinopodioides against atherosclerosis(AS). ApoE~(-/-) mice were fed on a high-fat diet for eight weeks to induce an AS model. The model mice were randomly divided into a model group, a positive control group, and low-, medium-and high-dose groups of total flavonoids of Z. clinopodioides, while C57BL/6J mice fed on a common diet were assigned to the blank group. The serum and aorta samples were collected after intragastric administration for 12 weeks, and the serum levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein-cholesterol(LDL-C), and high density lipoprotein-cholesterol(HDL-C) were detected by an automatic biochemical analyzer. The serum expression levels of intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), matrix metalloproteinase-2(MMP-2), and matrix metalloprotei-nase-9(MMP-9) were detected by enzyme-linked immunosorbent assay(ELISA). Oil red O staining was used to observe the aortic plaque area in mice. Hematoxylin-eosin(HE) staining was used to observe the aortic plaque and pathological changes in mice. The expression of P62 and LC3 in the aorta was detected by the immunofluorescence method. The protein expression of LC3Ⅱ/Ⅰ, Beclin-1, P62, p-PI3K, p-Akt, and p-mTOR in the aorta of mice was detected by Western blot. The results showed that compared with the blank group, the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2 and MMP-9 in the model group were significantly increased(P<0.01 or P<0.05), the content of HDL-C was decreased(P<0.05), intra-aortic plaque area was enlarged(P<0.01), the expression of LC3 in the aorta was significantly down-regulated, P62 expression was up-regulated(P<0.01 or P<0.05), the expressions of LC3Ⅱ/Ⅰ and Beclin-1 in the aortic lysate were significantly down-regulated, and the expressions of p-PI3K, p-Akt, p-mTOR and P62 were significantly increased(P<0.01). The medium-and high-dose groups of total flavonoids of Z. clinopodioides could reduce the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2, and MMP-9 in AS model mice(P<0.01 or P<0.05), and increase the content of HDL-C(P<0.01 or P<0.05). The aortic plaque area of mice after middle and high doses of total flavonoids of Z. clinopodioides was significantly reduced(P<0.01), the content of foam cells decrease, and the narrowing of the lumen decreased. The total flavonoids of Z. clinopodioides significantly increased the expression of LC3 in the aorta and the expression of LC3Ⅱ/Ⅰ and Beclin-1 in the lysate, and decreased the expression of P62 in the aorta and the expression of p-PI3K, p-Akt, p-mTOR and P62 in the lysate(P<0.01 or P<0.05). The results showed that the total flavonoids of Z. clinopodioides could improve the content of blood lipids and inflammatory factors, and reduce the generation of foam cells and plaques in aortic tissue, and the mechanism may be related to the regulation of PI3K/Akt/mTOR signaling pathway.

Adverse reactions and precautions of teprotumumab in the treatment of thyroid-associated ophthalmopathy / 国际眼科杂志(Guoji Yanke Zazhi)

Thyroid-associated ophthalmopathy(TAO)is an autoimmune disease associated with thyroid dysfunction that can significantly impact quality of life, result in visual impairment and facial disfigurement. Traditional treatments are often unsatisfactory. Studies have shown that teprotumumab, a human monoclonal antibody that can inhibit insulin-like growth factor 1 receptor(IGF-1R), has become an emerging targeted drug for TAO. Although the drug has proven to be effective and relatively safe in the treatment of TAO, adverse reactions are worthy of attention of ophthalmologists with the continuous promotion of clinical application, including hearing impairment, hyperglycemia, diarrhea, muscle spasms, infusion reactions, cognitive decline, thyroid suppression, alopecia, nausea and fatigue. Teprotumumab was generally well tolerated, with most adverse events being mild or moderate in severity. This paper aims to review the adverse reactions and precautions of teprotumumab in the treatment of TAO.

Role ofdenervation on kidney tubulointerstitial fibrosis induced by ischemia reperfusion injury via Nrf2/TGF-β pathway / 中华器官移植杂志

Objective:To explore the role of denervation on kidney tubulointerstitial fibrosis(TIF)induced by ischemia reperfusion injury(IRI)via NF-E2-related factor-2 (Nrf2)/transforming growth factor-β(TGF-β)pathway in mice.Methods:C57BL/6 mice were randomized into four groups(n=12 each)of sham, kidney ischemia reperfusion(IR), RDN and RDN+ IR(DIR). At Days 1 and 7 post-reperfusion, kidney histology and fibrotic injury are observed after hematoxylin-eosin(HE)and Masson staining.α-SMA protein is detected by immunohistochemistry.The serum levels of blood urea nitrogen(BUN), creatinine(Cr)and neutrophil gelatinase-associated lipocalin(NGAL)are measured.And the contents of superoxide dismutase(SOD), malondialdehyde(MDA), interleukin 4(IL-4), interleukin 10(IL-10)and interleukin 13(IL-13)in kidney tissues are detected.Western blot is utilized for observing the expression levels of Nrf2, TGF-β and phospho-Smad3 protein in kidney tissues.Results:Compared with sham group, kidney histologic score, serum levels of BUN, Cr and NGAL and contents of MDA, IL-4, IL-10 and IL-13 in kidney tissues spiked while activity of SOD declined.Protein expressions of Nrf2, TGF-β and phospho-Smad3 rise in IR-1 and DIR-1 groups( P<0.05). Compared with IR-7 group, degree of fibrosis and levels of α-SMA, IL-4, IL-10 and IL-13 drop in DIR-7 group, Nrf2 protein expression increased and protein expressions of TGF-β and phospho-Smad3 decreased( P<0.05). Conclusions:Acute oxidative stress injury induced by IRI becomes aggravated after kidney denervation and initiates TIF.The long-term expression of TGF-β and phosphorylation of Smad3 are suppressed due to a continuous activation of Nrf2 pathway, thereby blunting the long-term TIF degree of kidney.

The p21-activated kinases in neural cytoskeletal remodeling and related neurological disorders

The serine/threonine p21-activated kinases (PAKs), as main effectors of the Rho GTPases Cdc42 and Rac, represent a group of important molecular switches linking the complex cytoskeletal networks to broad neural activity. PAKs show wide expression in the brain, but they differ in specific cell types, brain regions, and developmental stages. PAKs play an essential and differential role in controlling neural cytoskeletal remodeling and are related to the development and fate of neurons as well as the structural and functional plasticity of dendritic spines. PAK-mediated actin signaling and interacting functional networks represent a common pathway frequently affected in multiple neurodevelopmental and neurodegenerative disorders. Considering specific small-molecule agonists and inhibitors for PAKs have been developed in cancer treatment, comprehensive knowledge about the role of PAKs in neural cytoskeletal remodeling will promote our understanding of the complex mechanisms underlying neurological diseases, which may also represent potential therapeutic targets of these diseases.

Preliminary clinical analysis of concurrent chemoradiotherapy combined with nituzumab for inoperable locally advanced esophageal cancer / 中华放射肿瘤学杂志

Objective:The standard treatment for inoperable locally advanced esophageal cancer is concurrent chemoradiotherapy, but the survival was not satisfied. Nituzumab is a humanized IgG monoclonal antibody against EGFR. The purpose of this study is to investigate the toxicity and efficacy of concurrent chemoradiotherapy combined with nituzumab for locally advanced esophageal cancer.Methods:We retrospectively reviewed the clinical data of locally advanced esophageal cancer who were treated with concurrent chemoradiotherapy combined with nituzumab in Peking University Cancer Hospital from June 2015 to June 2020. Kaplan- Meier method was used for analysis. Results:Thirty Patients were enrolled this study.After a median follow-up of 22.5 months, The objective response rate was 93%. The 1-year, 2-year, 3-year overall survival rates were 83%, 57% and 41%, with the progression-free survival rates 75%, 47% and 32%, with the local-recurrence free survival rates 83%, 53% and 37%, with the metastasis-free survival rates 75%, 51% and 36%, respectively.The incidence of grade≥3 hematological toxicity was 32%. There were 16% patients experiencing grade≥3 esophagitis.Conclusion:The preliminary result of concurrent chemoradiotherapy combined with nituzumab is effective and safe for patients with locally advanced esophageal cancer.

Establishment and Application of Rationality Evaluation Criteria for Tumor Nutritional Standardized Treatment / 中国药房

OBJECTIVE：To establish the eva luation criteria for the rationality of tumor nutritional standardized treatment ，and to provide reference for nutritional standardized treatment in tumer patients . METHODS ：Based on domestic and foreign guidelines or expert consensus ，the rationality evaluation standard of tumor nutritional standardized treatmentwas formulated in our hospital （Bozhou Municipal People ’s Hospital ）. 50 nutritional treatment medical records in our hospital from Jan. to Jun. 2019 were evaluated by weighted TOPSIS ；according to the evaluation results ，nutritional intervention was carried out ，and 50 nutritional treatment medical records （group B ）from Aug. to Dec. 2019 were re-evaluated by the same method after intervention. RESULTS ： The established evaluation criteria for the rationality of tumor nutritional standardized treatment in our hospital included 18 indicators，such as malnutrition diagnosis ，description of the nature of malnutrition ，nutrition screening and evaluation ，etc. After analysis ，the rational rate of nutritional treatment was only 18％ in group A （Ci of ideal solution with 9 medical records≥0.6），and 78％ in group B （Ci of ideal solution with59 medical records ≥0.6）. There was statistical significance in the rationality of nutritional treatment before and after nutritional intervention （Ci≥0.6）（P＜0.05）. CONCLUSIONS ：The established rational evaluation method of tumor nutritional standardized treatment is feasible ，and the evaluation results are intuitive and reasonable. Nutrition intervention is helpful to reduce the irrational rate of nutritional treatment.

Long Non-coding RNA CASC15 Promotes Intrahepatic Cholangiocarcinoma Possibly through Inducing PRDX2/PI3K/AKT Axis / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Intrahepatic cholangiocarcinoma (ICC) is one of the most common liver primary tumors but its treatments are limited. Bioinformatics showed that the expression level of long non-coding RNA cancer-associated susceptibility 15 gene (CASC15) is correlated with ICC progression, but its functional mechanism remains unclear. @*Materials and Methods@#Tissues from ICC patients, tumor and adjacent tissue, were used for detection of the expression of CASC15. Clinical data were also collected for clinicopathologic and survival analysis. Short interfering RNA and lentiviral short hairpin RNA were used to knock down CASC15 and PRDX2 expression in ICC cell lines, for the analysis of changes of cell function and xenografts. RNA-pulldown and RNA immunoprecipitation assays were used to detect RNA-binding protein, PRDX2. Male nude mice were used for ICC xenografts, and livers were collected after 4 weeks for immunohistochemistry. @*Results@#CASC15 is highly expressed in ICC tissues and is related to higher TNM stage. Knockdown of CASC15 in ICC cells reduced cell proliferation, migration, invasiveness and increased apoptosis, and G1/S block. PRDX2 bound to CASC15. Knockdown of CASC15 decreased PRDX2 expression which was rescued by the inhibition of proteasome formation. Downregulation of PRDX2 resulted in G1/S block, reduced ICC cell invasion. Downregulation of CASC15 inhibited phosphoinositide 3-kinase (PI3K)/AKT/c-Myc pathway through downregulating of PRDX2 and overexpressed PRDX2 rescued the block. CASC15 knockout in ICC xenografts suppressed tumor development in vivo, decreased the expression of PRDX2 and Ki67 and inhibited PI3K/AKT pathway. @*Conclusion@#CASC15 promotes ICC possibly by targeting PRDX2 via the PI3K/AKT pathway, indicating poor prognosis and high degree of malignancy of ICC.

Meta-analysis of efficacy and safety of sinomenine combined with methotrexate in treatment of rheumatoid arthritis / 中国中药杂志

To systemically evaluate the efficacy and safety of sinomenine combined with methotrexate(SIN+MTX) in the treatment of rheumatoid arthritis(RA). Literature databases of Wanfang, CNKI, VIP, SinoMed, PubMed, Cochrane Library and Web of Science were retrieved comprehensively for relevant clinical trials. The literature retrieval time was from database establishment to February 4, 2020. The quality of literatures was assessed by the Cochrane Evaluation Handbook 5.1.0, and qualified literature was reviewed and analyzed by using the RevMan 5.3 statistical software. Twenty randomized controlled trials met the inclusion criteria, and were enrolled in the Meta-analysis. The results showed that SIN+MTX remarkably reduced DAS28(MD=-0.85, 95%CI[-1.03,-0.67], P<0.000 01), and improved total efficiency(P<0.000 01). SIN+MTX could inhibit swollen joint count(MD=-1.19, 95%CI[-1.75,-0.63], P<0.000 1), tender joint count(MD=-1.58, 95%CI[-2.89,-0.28], P=0.02) and reduce morning stiffness time(MD=-8.44, 95%CI[-11.82,-5.07], P<0.000 01) compared with control group. The results showed that SIN+MTX was equal to control group in grip strength(SMD=0.20,95%CI[-1.11,1.51],P=0.77). SIN+MTX remarkably alleviated the erythrocyte sedimentation rate(MD=-9.87, 95%CI[-14.52,-5.22], P<0.000 1), C-reactive protein(SMD=-0.30, 95%CI[-0.51,-0.09], P=0.005), and rheumatoid factor(MD=-11.23,95%CI[-13.81,-8.65],P<0.000 01). The frequency of adverse reactions were reduced compared with that in the control group(P<0.000 01). Current clinical studies demonstrate that the efficacy and safety of SIN+MTX in the treatment of RA were superior to control group. However, due to the low quality and quantity of the included studies, high-quality randomized controlled trials are necessary to support the clinical evidences.

Effects of ATRA on diabetic rats with renal ischemia-reperfusion injury

Abstract Purpose To explore the role of all-trans retinoic acid (ATRA) in renal ischemia/reperfusion injury of diabetic rats. Methods Sixty adult male rats were randomly divided into 6 groups, including sham group (S group), ischemia-reperfusion group (I/R group), ischemia-reperfusion+ATRA group (A group), diabetic group (D group), diabetic ischemia-reperfusion group (DI/R group), diabetic ischemia-reperfusion +ATRA group (DA group). The levels of creatinine (Cr), cystatin C (Cys-C) and β2-microglobulin (β2-MG) were measured. Morphology of renal tissue was observed under light microscope. Results DJ-1, Nrf2, HO-1 and caspase-3 were detected by western blot. DJ-1, Nrf2, HO-1 and caspase-3 in I/R group, D group and DI/R group was higher than that in S group. Compared with I/R group, Nrf2 and HO-1 in A group was decreased, but caspase-3 was increased. However, Nrf2 in DA group was higher than that in DI/R group, HO-1 and caspase-3 in DA group were lower than that in DI/R group. Compared with group S, Cr, Cys-C and β2-MG in I/R group, A group, D group, and DI/R group were higher. Whereas the levels of Cr, Cys-C, β2-MG and renal injury score in DA group were lower than those in DI/R group. Conclusion ATRA has a protective effect on renal ischemia-reperfusion injury in diabetic rats, maybe relating to DJ/Nrf2 pathway.

Chinese Medicine Sequential Therapy Improves Pregnancy Outcomes after Surgery for Endometriosis-Associated Infertility: A Multicenter Randomized Double-blind Placebo Parallel Controlled Clinical Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the efficacy and safety of Chinese medicine (CM) improving pregnancy outcomes after surgery for endometriosis-associated infertility.@*METHODS@#A multicenter, randomized, double-blind placebo parallel controlled clinical trial was designed. A total of 202 patients who had laparoscopy for endometriosis-associated infertility with qi stagnation and blood stasis syndrome were included and randomly divided into the CM treatment group and placebo control group at a ratio of 1:1 using a central block randomization from May 2014 to September 2017, 101 patients in each group. The two groups received continuous intervention at 1-5 days after surgery, for 6 menstrual cycles. Before ovulation, the CM group was treated Huoxue Xiaoyi Granule (); after ovulation, Bushen Zhuyun Granule ( was involved. The control group was treated with placebo. Transvaginal ultrasonography was performed every menstrual cycle during the treatment, and female hormone levels in the follicular and luteal phases were measured during the 1st, 3rd and 6th menstrual cycles. The analysis was continued until pregnancy. The primary outcomes were clinical pregnancy rate and pregnancy outcome, and the secondary outcomes were follicular development and endometrial receptivity. Safety evaluations were performed before and after treatment.@*RESULTS@#(1) Clinical pregnancy and live birth rates: the clinical pregnancy and live birth rates of the CM group were significantly higher than those of the placebo group [44.6% (45/101) vs. 29.7% (30/101), 34.7% (35/101) vs. 20.8% (21/101), both P0.05).@*CONCLUSION@#Strategies for activating blood circulation-regulating Gan (Liver)-tonifying Shen (Kidney) sequential therapy can effectively improve the clinical pregnancy rate and live birth rate of endometriosis-associated infertility with qi stagnation and blood stasis after laparoscopy, improve follicular development, promote ovulation, improve endometrial receptivity, while being a safe treatment option. (Trial registration No. NCT02676713).

Association between serum estradiol level on the human chorionic gonadotrophin administration day and clinical outcome / 中华医学杂志(英文版)

Background:@#Estradiol, as an important hormone in follicular development and endometrial receptivity, is closely related to clinical outcomes of fresh in vitro fertilization embryo transfer (IVF-ET) cycles. The aim of this retrospective study was to evaluate the association between elevated serum estradiol (E2) levels on the day of human chorionic gonadotrophin (hCG) administration and IVF-ET pregnancy and birth outcomes.@*Methods:@#A total of 1771 infertile patients with their first fresh IVF-ET cycles were analyzed retrospectively between January 2011 and January 2016 in Peking University First Hospital. Patients were categorized by serum E2 levels on the day of hCG administration into six groups: group 1 (serum E2 levels ≤ 1000 pg/mL, n = 205), group 2 (serum E2 levels 1001–2000 pg/mL, n = 457), group 3 (serum E2 levels 2001–3000 pg/mL, n = 425), group 4 (serum E2 levels 3001–4000 pg/mL, n = 310), group 5 (serum E2 levels 4001–5000 pg/mL, n = 237), and group 6 (serum E2 levels > 5000 pg/mL, n = 137). The retrieved oocyte and MII oocyte numbers and implantation and clinical pregnancy rates of the groups were compared as the first objective of the study. For the 360 women with singleton births among all patients, the area under the corresponding receiver operating characteristic curve (ROC curve) was calculated to assess the predictive value of the E2 change for the probability of low birth weight (LBW) infants as the second objective.@*Results:@#The retrieved oocyte and MII oocyte numbers and implantation and clinical pregnancy rates gradually increased from groups 1 to 5 but decreased in group 6. The parameters of group 1 were statistically worse than those of the other groups, from group 2 to group 6 (the number of retrieved oocytes, t = 13.096, t = 23.307, t = 23.086, t = 26.376, t = 19.636, P < 0.003; the number of retrieved MII oocytes, t = 10.856, t = 20.868, t = 21.874, t = 23.374, t = 19.092, P < 0.003; the implantation rate, χ2 = 12.179, χ2 = 22.239, χ2 = 23.993, χ2 = 23.344, χ2 = 16.758, P < 0.003; the clinical pregnancy rate, χ2 = 16.415, χ2 = 28.074, χ2 = 35.387, χ2 = 37.025, χ2 = 24.590, P < 0.003). ROC analysis revealed that when a serum peak E2 of 3148 pg/mL was used to predict LBW.@*Conclusions:@#The results indicate that serum E2 levels have a concentration-dependent effect on clinical outcomes. The optimal range of the E2 level during a fresh IVF-ET cycle is 1000 to 3148 pg/mL.

Association between serum estradiol level on the human chorionic gonadotrophin administration day and clinical outcome / 中华医学杂志(英文版)

BACKGROUND@#Estradiol, as an important hormone in follicular development and endometrial receptivity, is closely related to clinical outcomes of fresh in vitro fertilization embryo transfer (IVF-ET) cycles. The aim of this retrospective study was to evaluate the association between elevated serum estradiol (E2) levels on the day of human chorionic gonadotrophin (hCG) administration and IVF-ET pregnancy and birth outcomes.@*METHODS@#A total of 1771 infertile patients with their first fresh IVF-ET cycles were analyzed retrospectively between January 2011 and January 2016 in Peking University First Hospital. Patients were categorized by serum E2 levels on the day of hCG administration into six groups: group 1 (serum E2 levels ≤ 1000 pg/mL, n = 205), group 2 (serum E2 levels 1001-2000 pg/mL, n = 457), group 3 (serum E2 levels 2001-3000 pg/mL, n = 425), group 4 (serum E2 levels 3001-4000 pg/mL, n = 310), group 5 (serum E2 levels 4001-5000 pg/mL, n = 237), and group 6 (serum E2 levels > 5000 pg/mL, n = 137). The retrieved oocyte and MII oocyte numbers and implantation and clinical pregnancy rates of the groups were compared as the first objective of the study. For the 360 women with singleton births among all patients, the area under the corresponding receiver operating characteristic curve (ROC curve) was calculated to assess the predictive value of the E2 change for the probability of low birth weight (LBW) infants as the second objective.@*RESULTS@#The retrieved oocyte and MII oocyte numbers and implantation and clinical pregnancy rates gradually increased from groups 1 to 5 but decreased in group 6. The parameters of group 1 were statistically worse than those of the other groups, from group 2 to group 6 (the number of retrieved oocytes, t = 13.096, t = 23.307, t = 23.086, t = 26.376, t = 19.636, P < 0.003; the number of retrieved MII oocytes, t = 10.856, t = 20.868, t = 21.874, t = 23.374, t = 19.092, P < 0.003; the implantation rate, χ = 12.179, χ = 22.239, χ = 23.993, χ = 23.344, χ = 16.758, P < 0.003; the clinical pregnancy rate, χ = 16.415, χ = 28.074, χ = 35.387, χ = 37.025, χ = 24.590, P < 0.003). ROC analysis revealed that when a serum peak E2 of 3148 pg/mL was used to predict LBW.@*CONCLUSIONS@#The results indicate that serum E2 levels have a concentration-dependent effect on clinical outcomes. The optimal range of the E2 level during a fresh IVF-ET cycle is 1000 to 3148 pg/mL.

Vascular endothelial growth factor is up-regulated by leukemia inhibitory factor and interleukin-6 in human endometriotic stromal cells / 中华妇产科杂志

Objective To compare the expression of leukemia inhibitory factor (LIF), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in tissue and fluid samples from patients with endometriosis, and investigate whether LIF and IL-6 regulate VEGF in human endometriotic stromal cells (ESC). Methods The levels of VEGF, LIF, IL-6 in serum, peritoneal fluid of patients with and without endometriosis were measured by ELISA. The mRNA of these three factors in the ectopic and eutopic endometrial tissue and stromal cells were measured by real-time PCR. ESC derived from ovarian endometriomas were cultured using the method of primary cell culture with LIF and IL-6, and the level of VEGF mRNA and protein were measured by the method of real-time PCR and ELISA respectively.Results VEGF and IL-6 concentration were 1.2 and 1.3 times higher in the serum of patients with endometriosis than in the control group [(94±19) versus (78±17) ng/L; (45±14) versus (35±9) ng/L; all P<0.05]. VEGF and IL-6 concentration were 1.2 and 1.4 times higher in the peritoneal fluid of patients with endometriosis than in the control group [(110±25) versus (91±21) ng/L; (69±20) versus (49±15) ng/L; all P<0.05]. VEGF and IL-6 concentrations in peritoneal fluid of patients with endometriosis were 1.2 and 1.5 times higher than in serum (all P<0.01). VEGF, LIF and IL-6 mRNA expression were 2.2, 8.6, 44.7 times higher in ESC compared with the matching eutopic endometrial stromal cells (all P<0.01). LIF and IL-6 mRNA were 2.0 and 64.8 times higher in ectopic endometrial tissue than the matching eutopic endometrial tissue (all P<0.05).ESC cultured with LIF, IL-6 and LIF+IL-6 induce VEGF protein secretion [(106±18), (124±30), (140±27) ng/L] by 1.3 , 1.5 and 1.7 times (all P<0.05). Conclusion Overexpression of LIF and IL-6 may synergistically contribute to upregulation of VEGF in ESC and promote development of endometriosis.

Effects of the Kunlun snow chrysanthemum polysaccharides on acetaminophen-induced oxidative stress, inflammation and apoptosis using animal model

To investigate the preventive effect of Kunlun snow chrysanthemum polysaccharides [KSCP] on acetaminophen [AP] induced liver damage and its possible mechanism. Mice acute liver injury model was established via intraperitoneal injection of AP [300 mg/kg]. The biochemical indicators of plasma and liver tissue were tested. The effects of KSCP on the liver index were examined. The liver pathological changes were investigated. The expressions of related protein were detected via Western blotting. In our study, compared with model group, the concentrations and contents of ALT, AST, TNF-alpha, IL-1beta and MDA were reduced and activities of SOD were increase in H-KSCP [1.2mg/10 g]-pretreated mice [P<0.01]. The liver index was significantly reduced in H-KSCP-pretreated mice compared with model group [4.89+/-0.22 vs 7.4+/-0.66, P<0.01]. Liver cellular swelling, degeneration and necrosis relieved, and pathological injury had been improved. Western blotting results showed that the caspase-3 protein level in H-KSCP group was significantly decreased, expression of Bcl-2 protein and Bcl-2/Bax ratio was increased, whereas which of Bax protein was decreased [P<0.01]. KSCP-pretreated at middle and high doses can prevent against the liver injury, its action mechanism may be related to its anti-inflammatory effects and regulation of apoptosis related proteins expression. Overall, our results showed that KSCP may be an effective preventive agent in preventing acute liver injury

Chitosan coated chlorogenic acid and rutincomposite phospholipid liposomes: Preparation, characterizations, permeability and pharmacokinetic

In order to research and enhance bioavailability of chlorogenic acid and rutin[CA-R] via the oral route, chitosan coated composite phospholipid liposomes [C-CPLs] were applied to study on preparation, permeability and pharmacokinetic of C-CA-R-CPLs. TheC-CA-R-CPLs were prepared by the method of ethanol injection. The entrapment efficiency [EE], average particle sizes, polymer disperse index [PDI], zeta potential, shape and in vitro drug release were investigated to characterize physicochemical parameters of C-CA-R-CPLs. The penetration properties from C-CA-R-CPLs were studied through Caco-2 cells model and the pharmacokinetics in Sprague-Dawley [SD] rats were evaluated by rat jugular vein intubation tube. The EE of C-CA-R-CPLs of CA and R was 91.3+/-2.13% and 92.6+/-2.44%, particle size of C-CA-R-CPLs was 176.7+/-2.3 nm, PDI was 0.207+/-0.014 and zeta potential of 12.61+/-1.33 mV. CA-RCPLs and C-CA-R-CPLs were spherical or elliptical sphere and the bilayer of the CPL was observed obviously under transmission electron. The C [max], t1/2 and AUC[0-12] h values of CA and R for groups of C-CA-R-CPLs were significantly increased.In conclusion, TheC-CA-R-CPLs as a novel nano-formulation have potential to be used to enhance the oral bioavailability of poorlywater-soluble drugs after oral administration

Optimization and in vitro evaluation of TAT and PEG co-modified tilianin-loaded composite phospholipid liposomes / 中草药

Objective To optimize the preparation technology of transcription activator (TAT) and polyethylene glycols (PEG) co-modified tilianin-loaded composite phospholipid liposome (TAT & PEG tilianin CPL, T&PTCPL) and investigate its protective effect on cardiomyocytes. Methods The composite phospholipid liposome was prepared by thin film-ultrasonic method. A three- factor, three-level Box-Behnken experimental design was employed. The weight ratio of total phospholipid to tilianin (X1), the concentration of DSPE-PEG2000-TAT (X2), and hydration volume (X3) were observed. The encapsulation efficiency (Y1), particle size (Y2), and polydispersion coefficient (Y3) were evaluated to optimize optimal formula. In addition, hypoxia/reoxygenation model was established with Na2S2O4 in H9C2 cells. Superoxide dismutase (SOD) activity, malonaldehyde (MDA) level and release of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) were assessed to evaluate the effect of T&PTCPL, meanwhile, the in vitro release rate (dynamic dialysis method) and absorption rate of tilianin and T&PTCPL in Caco-2 cell were examined. Results The optimal formula was as following: X1 = 20, X2 = 1.7%, and X3 = 3.2 mL; The encapsulation efficiency was (86.62 ± 2.51)%, particle size was (149.7 ± 8.2) nm and PDI was 0.15 ± 0.05. Compared with model group, T&PTCPL and tilianin groups increased SOD activity, inhibited level of MDA, LDH and CK-MB leakage (P < 0.05), and the effect of T&PTCPL group was better than tilianin group, meanwhile, T&PTCPL was completely released at 48 h, with a cumulative release of 88.65%, and Caco-2 cells had better absorption of T&PTCPL. Conclusion The Box-Behnken design is suitable for optimizing the formulation of T&PTCPL, and the observed responses are in close agreement with the predicted values of the mathematic models; Moreover, T&PTCPL shows a better sustained release effect in vitro release, which promots the absorption of tilianin in Caco-2 cells and suggests that T&PTCPL may have protective effect on myocardial ischemia reperfusion injury.

Effect of tert-butylhydroquinone on DJ-1∕Nrf2 pathway during renal ischemia-reperfusion in diabet-ic rats / 中华麻醉学杂志

Objective To evaluate the effect of tert-butylhydroquinone ( t-BHQ) on DJ-1∕nuclear factor erythroid 2-related factor 2 (Nrf2) pathway during renal ischemia-reperfusion (I∕R) in diabetic rats. Methods Forty SPF healthy adult male Sprague-Dawley rats, weighing 200-220 g, were divided into 4 groups (n＝10 each) using a random number table method: control group (group C), diabetes mellitus group (group D), diabetes mellitus plus renal I∕R group (I∕R group) and t-BHQ group (group T). Diabe-tes mellitus was induced by intraperitoneal streptozotocin 60 mg∕kg and confirmed by fasting blood glucose level＞16. 7 mmol∕L 72 h later. t-BHQ 50 mg∕kg was intraperitoneally injected in 3 times at an interval of 8 h starting from 24 h before surgery in group T, while the equal volume of normal saline was given instead in D and I∕R groups. Blood samples were collected from the apex of the heart at 24 h of reperfusion for deter-mination of serum creatinine (Cr), cystatin C (Cys C) and β2-microglobulin (β2-MG) concentrations. The rats were then sacrificed, and kidneys were removed for determination of pathological changes of kidneys (with a light microscope) and for detection of the expression of DJ-1, Nrf2 and heme oxygenase-1 (HO-1) in renal tissues (by Western blot). Results Compared with group C, the concentrations of serum Cr, Cys C and β2-MG and pathological scores were significantly increased, and the expression of DJ-1, Nrf2 and HO-1 was up-regulated in D, I∕R and T groups ( P＜0. 05). Compared with group D and group I∕R, the concentrations of serum Cr, Cys C and β2-MG and pathological scores were significantly decreased, and the expression of DJ-1, Nrf2 and HO-1 was up-regulated in group T ( P＜0. 05). Conclusion t-BHQ can at- tenuate renal I∕R injury by activating DJ-1∕Nrf2 pathway in diabetic rats.

Protective Effects of Tilianin on Brain Tissue in Cerebral Ischemia-reperfusion Injury Model Rats / 中国药房

OBJECTIVE:To study the effects of tilianin(TIL)on brain tissue in rats with cerebral ischemia-reperfusion injury. METHODS:Totally 120 male SD rats were randomly divided into sham operation group(0.9% sodium chloride solution),model group(0.9% sodium chloride solution),nimodipine group(32 mg/kg)and TIL low-dose and medium-dose,high-dose groups(4, 8,16 mg/kg),with 20 rats in each group. The rats were given relevant medicine intragastrically,once a day,for consecutive 7 d. 15 min after last medication,cerebral ischemia-reperfusion injury model was established by reforming suture-occluded method. The neurological deficit score in rats were evaluated, and percentage of cerebral infarction volume of rats was determined. Histopathological changes of brain tissue were observed by HE staining. The activities of SOD,CAT and LDH,MDA content in cerebral tissue of rats were determined. The expression of calcitonin gene-related peptide(CGRP)and peripheral vascular endothelial growth factor receptor 2 (VEGFR2) protein were determined by Western blot assay. RESULTS:Compared with sham operation group,neurological deficit score and percentage of cerebral infarction volume of model group were increased significantly(P＜0.01);the nerve cells in brain tissue were significantly reduced and the interstitial edema was obvious. SOD and CAT activities were decreased significantly,LDH activity was increased significantly,MDA content was decreased significantly,protein expression of CGRP and VEGFR2were increased significantly(P＜0.05 or P＜0.01). Compared with model group,neurological deficit score of nimodipine group,TIL medium-dose and high-dose groups were decreased significantly;percentage of cerebral infarction volume was decreased significantly (P＜0.05 or P＜0.01);above pathological conditions of cerebral tissue in rats were relieved significantly;SOD and CAT activities were strengthened significantly,MDA content and LDH activities were decreased significantly,protein expression of CGRP and VEGFR2were increased significantly (P＜0.05 or P＜0.01). CONCLUSIONS: TIL has certain protective effects on cerebral ischemia-reperfusion injury model rats,and its mechanism may be related to the up-regulation of CGRP and VEGFR2expression.

Enhancing the in vitro release of total flavonoids extract from Dracocephalum moldavuca composite phospholipid liposomes optimized by response surface methodology

The present study was undertaken to optimize the preparation conditions of total flavonoids extract from Dracocephalum Moldavuca composite phospholipid liposome [TFDMCPL]by response surface methodology [RSM] and to investigate the in vitro release [IVR] of TFDMCPL. Method of ethanol injection was adopted to prepare TFDMCPL. The single factor experiments were used for the key experimental factors and their test range. Based on the single factor experiments, with encapsulation efficiency [EE] Size of TFDMCPL and polymey disperse index [PDI] as dependent variable, central composite design was adopted to optimize preparation technology by taking content of phospholipid and content of cholesterol as independent variables, fitting of various mathematical equations were performed using a statisitical software of Design-Expert 8.0.6. Preparation parameters were optimized through response surface plotted by optimum fitting equations, optimized procedure was validated through experimental preparation of TFDMCPL. Optimum preparation technology was as following: phospholipid 505mg and cholesterol 50mg. Under these condition, encapsulation efficiency was 90.2+/-1.2%, size of TFDMCPL was 115.6+/-4.3nm, PDI was 0.169+/-0.015 and Zeta potential was -15.38+/-0.5. These indicated that TFDMCPL with high entrapping efficiency and small particle size could be prepared by the ethanol injection method. And TFDMCPL were found to enhance the release of drugs more effectively than TFDM based on the in vitro model

Study on the Preventive Effect and Mechanism of Wei Medicine Kunlun Snow Chrysanthemum Polysaccha-rides on Carbon Tetrachloride-induced Acute Liver Injury in Mice / 中国药房

OBJECTIVE:To study the preventive effect and mechanism of Wei medicine Kunlun snow chrysanthemum polysac-charides(KSCP)on carbon tetrachloride(CCl4)-induced acute liver injury in mice. METHODS:96 mice were randomly divided in-to normal group(normal saline),model group(normal saline),Biphenyl diester dropping pill(positive control,1.5 mg/10 g)and KSCP low-dose,medium-dose,high-dose groups (0.3,0.6,1.2 mg/10 g),16 in each group,with intragastric administration, once a day,for 10 d. Except for normal group,mice in other groups were intraperitoneally injected 1%CCl4 rapeseed oil solution to induce liver injury. After 24 h of modeling,the levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),tu-mor necrosis factor α(TNF-α),interleukin 1(IL-1)in serum,levels of malondialdehyde(MDA),superoxide dismutase(SOD) in liver tissue were detected;the liver,spleen indexes were calculated. Pathological changes of liver tissue were observed,patho-logical scoring was conducted. The protein expressions of apoptosis-related genes Caspase-3,Bcl-2,Bax in liver tissue were detect-ed. RESULTS:Compared with normal group,levels of ALT,AST,TNF-α,IL-1 in serum,MDA level in liver tissue and liver, spleen indexes in model group were obviously increased(P<0.01);SOD level in liver tissue was decreased(P<0.01);pathologi-cal changes in hepatocellular necrosis,degeneration and inflammatory cell infiltration,and pathological score in model group was obviously increased(P<0.01);caspase-3 protein expression and Bcl-2/Bax ratio in liver tissue in model group were obviously de-creased (P<0.01). Compared with model group,above-mentioned indexes in each administration group were obviously improved (P<0.05 or P<0.01). CONCLUSIONS:KSCP has certain preventive effect on CCl4-induced acute liver injury in mice,and its mechanism may be associated with anti-oxidation,anti-inflammation and regulation of apoptosis-related protein expressions.