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Marsdenia tenacissima injection, a standard Marsdenia tenacissima extract (MTE), has been approved as an adjuvant therapeutic agent for various cancers. Our previous study showed that MTE inhibited the proliferation and metastasis of prostate cancer (PCa) cells. However, the underlying mechanisms and active ingredients of MTE against PCa were not completely understood. This study revealed that MTE induced significant decreases in cell viability and clonal growth in PCa cells. In addition, MTE induced the apoptosis of DU145 cells by reducing the mitochondrial membrane potential and increasing the expression of Cleaved Caspase 3/7, Cyt c, and Bax. In vivo, DU145 xenografted NOD-SCID mice treated with MTE showed significantly decreased tumor size. TUNEL staining and Western blot confirmed the pro-apoptotic effects of MTE. Network pharmacology analysis collected 196 ingredients of MTE linked to 655 potential targets, and 709 PCa-associated targets were retrieved, from which 149 overlapped targets were screened out. Pathway enrichment analysis showed that the HIF-1, PI3K-AKT, and ErbB signaling pathways were closely related to tumor apoptosis. Western blot results confirmed that MTE increased the expression of p-AKTSer473 and p-GSK3βSer9, and decreased the expression of p-STAT3Tyr705in vitro and in vivo. A total of 13 compounds in MTE were identified by HPLC-CAD-QTOF-MS/MS and UPLC-QTOF-MS/MS. Molecular docking analysis indicated that six compounds may interact with AKT, GSK3β, and STAT3. In conclusion, MTE induces the endogenous mitochondrial apoptosis of PCa by regulating the AKT/GSK3β/STAT3 signaling axis, resulting in inhibition of PCa growth in vitro and in vivo.
Subject(s)
Mice , Animals , Male , Humans , Mice, Inbred NOD , Mice, SCID , Marsdenia , Proto-Oncogene Proteins c-akt , Glycogen Synthase Kinase 3 beta , Molecular Docking Simulation , Phosphatidylinositol 3-Kinases , Tandem Mass Spectrometry , Prostatic Neoplasms , Apoptosis , STAT3 Transcription FactorABSTRACT
Angiopoietin-like protein 4 (ANGPTL4) is involved in the regulation of glucose and lipid metabolism and angiogenesis, and is closely related to tumorigenesis, development, invasion and metastasis. The abnormal expression of ANGPTL4 gene can promote or inhibit the growth and proliferation of tumor cells and play a tumor-promoting or anti-tumor role in the occurrence and development of tumors. To explore the role of ANGPTL4 gene in the occurrence and development of different tumors can provide reference for evaluating the diagnosis, prognosis and curative effect of tumors.
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IgG4-related hepatobiliary and pancreatic diseases are a part of the IgG4-related disease multiorgan fibroinflammatory disorder, including IgG4-related autoimmune pancreatitis, IgG4-related sclerosing cholangitis, and IgG4-related hepatic involvement. The main pathological features include IgG4 + plasma cell/lymphocyte infiltration, storiform fibrosis, obliterative phlebitis, and eosinophil infiltration. The diagnosis of this disease is often based on the comprehensive diagnostic criteria for IgG4-related diseases and organ-specific diagnostic criteria. However, it is difficult to differentiate IgG4-related hepatobiliary and pancreatic diseases from neoplastic diseases, and novel diagnostic biomarkers are expected to improve the sensitivity and specificity of diagnosis. To date, glucocorticoids remain the first-line drug for this disease, and biological agents, especially anti-CD20 monoclonal antibody, may be an alternative therapy for patients with corticosteroid contraindication/intolerance or recurrent/refractory disease.
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IgG 4 related disease (IgG 4-RD) is an immune medicated rare disease, characterized with chronic inflammation and fibrosis in the involved organs, it is a systemic disease affected nearly every anatomic site of the body, usually involvement of multiple organs, and with diverse clinical manifestations. Due to the the relative novelty of the disease and under-recognition, the overall level of diagnosis and treatment in China is uneven. Till now, there is no relevant expert consensus or guidance of IgG 4-RD in China. In order to further improve the understanding and standardize the management of IgG 4-RD, on the basis of summarizing domestic and international experience, the China Alliance For Rare Diseases, together with the Chinese Rheumatology Association, organized an expert group and established the Chinese expert consensus on the diagnosis and treatment of IgG 4 related diseases.
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Objective To improve the recognition of ectopic adrenocorticotropic hormone syndrome.Methods The diagnosis and treatment of a 43 years old female patient with multiorgan involvement mimic dermatomyositis was analyzed and discussed.Results The patient presented with fatigue,edema,skin pigmentation,neuropsychiatric abnormalities,hypertension,hypokalemia,hyperglycemia and other systemic involvement,was finally diagnosed with ectopic adrenocorticotropic hormone syndrome caused by paragang-lioma of the anterior mediastinum.After surgical removal of the tumor,her clinical symptoms immediately relieved,meanwhile related hormone levels returned to normal.Conclusion Although paraganglioma-induced ectopic adrenocorticotropic hormone syndrome is rare in clinical practice,more attention should be paid to this specific situation.
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Hyaluronic acid (HA) is a natural ligand of tumor-targeted drug delivery systems (DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors (HARE and LYVE-1) are also overexpressing in the reticuloendothelial system (RES). Therefore, polyethylene glycol (PEG) modification of HA-based DDS is necessary to reduce RES capture. Unfortunately, pegylation remarkably inhibits tumor cellular uptake and endosomal escapement, significantly compromising the antitumor efficacy. Herein, we developed a Dox-loaded HA-based transformable supramolecular nanoplatform (Dox/HCVBP) to overcome this dilemma. Dox/HCVBP contains a tumor extracellular acidity-sensitive detachable PEG shell achieved by a benzoic imine linkage. The and investigations further demonstrated that Dox/HCVBP could be in a "stealth" state at blood stream for a long circulation time due to the buried HA ligands and the minimized nonspecific interaction by PEG shell. However, it could transform into a "recognition" state under the tumor acidic microenvironment for efficient tumor cellular uptake due to the direct exposure of active targeting ligand HA following PEG shell detachment. Such a transformative concept provides a promising strategy to resolve the dilemma of natural ligand-based DDS with conflicting two processes of tumor cellular uptake and nonspecific biodistribution.
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Objective@#To improve the recognition of ectopic adrenocorticotropic hormone syndrome.@*Methods@#The diagnosis and treatment of a 43 years old female patient with multiorgan involvement mimic dermatomyositis was analyzed and discussed.@*Results@#The patient presented with fatigue, edema, skin pigmentation, neuropsychiatric abnormalities, hypertension, hypokalemia, hyperglycemia and other systemic involvement, was finally diagnosed with ectopic adrenocorticotropic hormone syndrome caused by paraganglioma of the anterior mediastinum. After surgical removal of the tumor, her clinical symptoms immediately relieved, meanwhile related hormone levels returned to normal.@*Conclusion@#Although paraganglioma-induced ectopic adrenocorticotropic hormone syndrome is rare in clinical practice, more attention should be paid to this specific situation.
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Objective To explore the effect of low-level laser therapy (LLLT)applied to the quadriceps muscle on the recovery of exhausting-cycling-exercise-induced fatigue.Methods According to a randomised,double-blind and crossover design,16 healthy male students were randomly assigned to an LLLT-1,LLLT-3,LLLT-5 and a placebo group,and received LLLT for 300 s at the dosage of 0.06 J· cm-2,0.18 J·cm-2,0.3 J·cm-2 and 0 to the bilateral rectus femoris after the exhausting-cycling-exercise-induced fatigue.The blood lactate(BL),heart rate(HR),rated perceived exertion(RPE)and visual analogue scale(VAS)were assessed before the exercise,immediately after exercise,10 and 20 min after exercise,as well as immediately after the first Wingate(WG)test,5 and 30 min after the WG test.Meanwhile,the second WG test was performed 40 min after the first WG test.Results The average HR value of LLLT-1 group was significantly lower than the placebo group at 10 min after exercise(P＜ 0.05)and immediately after the WG test(P＜0.01),while that of LLLT-3 and LLLT-5 groups was significantly lower than the placebo group immediately and 5 min after the WG test(P＜0.01).Compared to the placebo group,the average BL of LLLT-1,LLLT-3 and LLLT-5 groups was significantly lower 10 min after exercise(P＜0.05 for all)and that of LLLT-5 group was also significantly lower 30 min after the first WG test(P＜0.05).However,the average blood glucose of LLLT-5 group was significantly higher than the placebo group right after the first WG test(P＜0.05).Moreover,significant increase was observed in the mean(P=0.002)and peak power(P=0.006)at the second WG test and the mean(P=0.048) power at the first WG test of LLLT-3 group,compared to the placebo group.Conclusion LLLT applied to quadriceps muscles after exhausting exercise may enhance recovery,and LLLT at the dose of 0.18 J·cm-2 is of the best effect.
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Objective To explore value of detecting fetal thymus size with the thymic-thoracic ratio (TT-ratio).Methods Prenatal ultrasonography examinations were performed on totally 317 normal singleton healthy pregnancies from 18 to 39 gestational weeks.The normal thymus of fetus were observed on the three-vessel-trachea (3VT) view.The anteroposterior diameter of the thymus (T1) was measured between the anterior border of the aortic arch and posterior border of sternum.The intrathoracic mediastinal diameter (T2) was measured between the anterior border of thoracic vertebral body and posterior border of sternum.The TT-ratio was then calculated as the ratio of T1 to T2.Scatter plot between TT-ratio and gestational age was drawn.And the Spearman regression analysis was performed.Results The thymus of fetus was shown as an irregular homogenous structure in the anterior mediastinum on the 3VT view.The mean TT-ratio was 0.45± 0.03.There was no correlation between TT-ratio and gestation (rs =0.06,P=0.29).Conclusion Prenatal ultrasound can display the thymus obviously.TT-ratio could be applied to assess the fetal thymus size,which can provides clinical basis for the detection of absent or hypoplastic thymus in fetus.
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Objective To evaluate values of Serum IgG 4,IgG4/IgG ratio,and IgG4/IgG1 ratio for distinguishing Mikulicz′s disease(MD)from primary Sj?gren′s syndrome(pSS).Methods It retrospectively analyzed 186 patients subjected to serum IgG subclass testing to differentiate MD from primary Sj?gren′s syndrome(pSS)at Peking University People′s Hospital from July 2012 to July 2016.This sample included 42 MD patients and 144 pSS patients.Serum IgG subclass concentrations were measured using Siemens reagents with nephelometry and BNⅡinstrument.In partial patients,serum antinuclear antibodies (ANA)were detected by indirect immunofluorescence assay, and serum anti-SSA antibodies and anti-SSB antibodies were detected by Western blot.Serum IgG subclass test results,ANA test results,serum anti-SSA antibody,and anti-SSB antibody test results were collected.The quantitative data were represented by median(quantile range).The Mann-Whitney U test was used to compare the medians between the two groups.Categorical variables were analyzed with a χ2test and were shown as percentages.The ROC curve was constructed to identify the optimal cut-off values and the area under the curve(AUC)values of the serum IgG4,IgG4/IgG ratio,and IgG4/IgG1 ratio for distinguishing MD patients from pSS patients.Results The medians of serum IgG4, IgG4/IgG ratio and IgG4/IgG1 ratio in MD patients were 11 200 mg/L(17 330),0.444(0.314)and 1.318(1.920), as compared with 329 mg/L(490),0.016(0.025)and 0.023(0.039)respectively in pSS patients(Z=-9.368, -9.560, and -9.571, respectively, P<0.001).For distinguishing MD from pSS, the optimal cut-off values of serum IgG4, IgG4/IgG ratio, and IgG4/IgG1 ratio were 1 870 mg/L,0.111, and 0.206, respectively.The corresponding AUC values were 0.976,0.985,and 0.986,respectively.Comparison of the ROC curves showed that there was no significant difference between AUC of serum IgG4/IgG ratio and IgG4/IgG1 ratio(Z=0.283, P=0.777).But AUC of serum IgG4/IgG ratio and IgG4/IgG1 ratio were significantly higher than AUC of serum IgG 4(Z=2.360 and 1.975,repectively,P=0.018 and 0.048,respectively).The positive rates of serum ANA in MD and pSS group were 10%and 85.8%,respectively(χ2=71.340,P<0.001).The positive rates of anti-SSA antibody and anti-SSB antibody in MD were 6.7%and 0%,respectively.Compared to 72.3%and 38.3%in pSS group, they were lower(χ2=44.773 and 16.792, P<0.001).Conclusions Measurements of serum IgG4 concentration,IgG4/IgG ratio, and IgG4/IgG1 ratio were of important values in differentiating MD from pSS.Serum IgG4/IgG ratio or IgG4/IgG1 ratio was superior to serum IgG4.
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Objective To explore the method of self-care management education for patients who have received the eyelid reconstruction surgery by transplanting with free flap-skin. Methods There were 11 cases (15 eyes) who achieved self-care management and continued nursing, including the preoperative, postoperative nursing care of the donor-skin area, eye nursing, diet guidance, medication guidance, safety protection and its like. Results None of the cases revealed infection and all the grafts showed good biological activity among the 11 cases (15 eyes). Conclusions After self-care management education and continued nursing, the averaged hospitalization days of the patients are shortened; the cost is reduced, and the successful rate of the eyelid′s construction by free skin-flap transplantation is enhanced. Self-care management education and continued nursing care played an important role in promoting the healing and improving the successful rate of eyelid′s skin-flap transplantation.
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Objective We reported 5 unusual cases of multiple myeloma (MM) initially presented as polyarthritis.Special attention should be paid to this very unusual scenario.Methods Five cases who presented initially as polyarthritis and finally diagnosed as MM were administered to Peking University People's Hospital and 11 cases from literature were reported.The clinical symptoms and laboratory parameters were analyzed respectively.Results The primarily affected joints were small joints,such as metacarpophalangeal joints,proximal interphalangeal joint,metatarsophalangeal and temporomandibular joints,but large joints such as wrists,elbows,shoulders,knees,ankle joints could be involved,too.Fourteen of 16 patients were misdiagnosed as rheumatoid arthritis (RA).Renal dysfunction presenting as high level of serum creatinine or proteinuria was detected in 14 cases.Laboratory tests showed elevated erythrocyte sedimentation rate or C reactive protein level in 13 cases.Anemia was detected in 9 cases.Hypercalcemia was detected in half of the patients.Hyperglobu-linemia was detected in 6 cases.The serum level of free M-protein was markedly elevated in 14 cases.Auto-antibodies were negative,except that rheumatoid factor was positive in 1 case.Conclusion It is important to pay attention to the clinical pictures presented as polyarthritis with negative autoantibodies,and associated with renal dysfunction,anemia and hypergammaglobulinemia.MM is important in the differential diagnosis.
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Objective To screen for the miR-155 expression in synovial fibroblasts of rheumatoid arthritis (RASFs) and osteoarthritis (OASFs) and to evaluate the function of miR-155 on RASFs and its possible target mRNAs. Methods The expression levels of miR-155 in RASFs and OASFs were detected by real-time PCR. MiR-155 mimic and miR-155 inhibitor, as well as scrambled control were transfected into cultured RASFs by Lipofectamine 2000. Forty-eight hours later, MMP-3 levels in the cell culture supernatant were detected by ELISA and fibroblast proliferation was assayed by 3H -TdR incorporation test. Fibroblast invasive ability was tested by transwell system. IKBKE which previously identified as actual target of miR-155 was examined by real-time PCR. Comparisons between groups were performed with t test or one-way ANOVA analysis. Results It was shown that miR-155 was up-regulated in RASFs (1.79 ±1.94) and it was higher than that in OASFst (0.11±0.17), P<0.05]. Up-regulation of miR-155 could decrease MMP-3 levels (P<0.05). The proliferation and invasion of RASFs transfected with miR-155 were both evidently suppressed (P<0.05), while reducing the endogenous miR-155 could significantly enhance RASF proliferation (P<0.05). The expression of IKBKE of RASFs transfected with miR-155 was obviously down-regulated compared to those transfected with the scrambled control (P<0.05). Conclusion miR-155 is up-regulated in RASFs which may be a protective factor against the inflammatory effect, at least partially by attenuating the expression of IKBKK.
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Objective: To observe the efficacy of herbal drug-partitioned moxibustion for sub-health status and its influence on humoral immunity, cellular immunity and blood rheology.Methods: By health evaluation in traditional Chinese medicine, the subjects were selected and applied with herbal drug-partitioned moxibustion on the acupoints selected upon pattern identification, in accordance with different causative reason, symptoms, clinical manifestations,to observe the changes in various physiochemical indexes and clinical symptoms before and after the treatments. Results: After herbal drug-partitioned moxibustion, the clinical symptoms were obviously improved, and obvious change took place in the activity of NK cells and in platelet aggregation, with statistic significance (P＜0.05) in comparison of those before moxibustion. Simultaneously, the contents of C3 and C4 decreased in humoral immunity after the treatment, and IgC content increased, with statistic significance (P＜0.05) in comparison of those before the treatment. Conclusion: Herbal drug-partitioned moxibustion can regulate the functions of qi and blood in those with sub-health, by balancing yin and yang in the body and invigorating the spirit and reinforcing qi, so as to relieve sub-health status, indicating its regulatory function on humoral immunity, cellular immunity and blood rheology of the human body.
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Objective:To explore the expression of GITR/GITRL in rheumatoid arthritis(RA)and its correlation with clinical features of the disease.Methods:Fifty three RA patients,35 osteoarthritis(OA)patients and 35 healthy volunteers were included in the study.The real-time-fluorescence quantitative PCR method was used to analyze the expression level of GITR/GITRL mRNA.Using fluorescence-activated cell sorting(FACS),the expression of GITR on CD4+CD25+ T cells in peripheral blood monouuclear cells(PBMC)was detected.The levels of Anti-CCP antibody,C-reactive protein(CRP),erythrocyte sedimentation rate(ESR)and rheumatoid factor(RF)of the RA patients were measured at the same time.Results:It was shown that the level of GITR/GITRL mRNA and the percentage of GITR+ T cells in the CD4+CD25+ T cell subpopulation[12.38?5.72/16.41?10.16,(28.12?16.85)%] were significantly higher than those of the OA group [9.59?5.87/12.09?7.53,(21.01?14.42)%,P
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Objective To understand the clinical profiles of arthritis after human parvovirus B19(B19) infection.Methods Four cases were described and the clinical and laboratory characteristics were analyzed. Results The median onset age of the 4 patients(2 females and 2 males)was 34 years old.Typical clinical manifestations included joint symptoms,flu-like malaise and erythematous rash.Anti-Bl9 IgM antibodies were all positive in 4 patients.B19 DNA was detected in blood samples of 3.Other types of arthritis were excluded. No relapses were noticed after followed-up of 1～3 years.Conclusion The Anti-B19 lgM and B19 DNA should be detected in patients suffer from arthritis with unknown origin.
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Objective To study the effects of fetal lamb cardiac bypass on the fetal cardiac function.Methods Eight ewes at gestation of 120 to 140 days have nine fetus which were randomly divided into control group (n = 4) and fetal bypass group (n = 5). Control group underwent sham procedure that fetal stemotomy was performed.Bypass group underwent fetal cardiac bypass with cen- trifugal pump and placenta for 30 minutes.Fetal mean blood pressure,heart rate and bleed gas data were recorded before bypass,30 minutes during bypass,1 hour after cessation of bypass,2 hour after cessation of bypass.Tei index of two ventricles and pulse index of umbilical arteries were recorded with ultrasonography.Plasma troponin I was assayed.Ultrastructure of fetal myocardium was recorded,Results Fetal mean blood pressure and heart rate of two groups have no changes during the experiment time.The umbilical pulse index of bypass group elevated significantly compared with control group (P