This article summarized the advances in the research of the natural products ET-743,Didemnin B and Aplidine,which were isolated from ascidians, and have been applied to clinical study at present.

Objective To evaluate the expression of human kallikrein10 (KLK10) in different endometrioid tissues and analyse the relationship of KLK10 with ER and PR in endometrioid adenoearcinoma.Methods The expression of KLK10 protein in 12 normal endometria,19 endometrial hyperplasia and 34 endometrial carcinoma were detected by immunohistochemistry.The correlations of the expression of KLK10 protein,ER and PR were analyzed.Results The expression of KLK10 in stage Ⅰ,Ⅱ and Ⅲ were 64.3 ％(9/14),30.0 ％ (3/10),10.0 ％ (1/10),and the difference was statistically significant (P ＜ 0.05).The expression of KLK10 in endometrial carcinoma,normal endometria,endometrial hyperplasia were 66.7 ％ (8/12),33.3 ％(4/12),10.0 ％ (1/10),and the difference was statistically significant (P ＜ 0.05).The expression of KLK10 in G1,G2,G3 were 66.7 ％,33.3 ％,10.0 ％,and the difference was statistically significant (P ＜ 0.05).The positive rate of KLK10 expression was 38.2 ％ and the positive rates of ER and PR expression were 67.6 ％and 55.9 ％,respectively,in 34 endometrial carcinoma.The expression of KLK10 was positively correlated with ER and PR expression (x2 =0.448,P ＜ 0.01).Conclusion Absence or down-regulated expression of KLK10 may play an important role in the formation and development of endometrioid adenocarcinoma.The low expression of KLK10 is correlated with low expression of ER and PR in endometrioid adenocarcinoma.The positive expression of KLK00,ER and PR predicts a better prognosis.

OBJECTIVETo investigate the effects of nano-lead exposure on learning and memory and iron homeostasis in the brain of the offspring rats on postnatal day 21 (PND21) and postnatal day 42 (PND42).

METHODSTwenty adult pregnant female Sprague-Dawley rats were randomly divided into control group and nano-lead group. Rats in the nano-lead group were orally administrated 10 mg/kg nano-lead, while rats in the control group were administrated an equal volume of normal saline until PND21. On PND21, the offspring rats were weaned and given the same treatment as the pregnant rats until 42 days after birth. The learning and memory ability of offspring rats on PND21 and PND42 was evaluated by Morris water maze test. The hippocampus and cortex s amples of offspring rats on PND21 and PND42 were collected to determine iron and lead levels in the hippocampus and cortex by inductively coupled plasma-mass spectrometry. The distributions of iron in the hippocampus and cortex were observed by Perl's iron staining. The expression levels of ferritin, ferroportin 1 (FPN1), hephaestin (HP), and ceruloplasmin (CP) were measured by enzyme-linked immunosorbent assay.

RESULTSAfter nano-lead exposure, the iron content in the cortex of offspring rats on PND21 and PND42 in the nano-lead group was significantly higher than those in the control group (32.63 ± 6.03 µg/g vs 27.04 ± 5.82 µg/g, P<0.05; 46.20 ±10.60 µg/g vs 36.61 ± 10.2µg/g, P<0.05). The iron content in the hippocampus of offspring rats on PND42 in the nano-lead group was significantly higher than that in the control group (56.9 ± 4.37µg/g vs 37.71 ± 6.92µg/g, P<0.05). The Perl's staining showed massive iron deposition in the cortex and hippocampus in the nano-lead group. FPNl level in the cotfex of offspring rats on PND21 in the nano-lead group was significantly lower than that in the control group (3.64 ± 0.23 ng/g vs 4.99 ± 0.95 ng/g, P<0.05). FPN1 level in the hippocampus of offspring rats on PND42 in the nano-lead group was significantly lower than that in the control group (2.28 ± 0.51 ng/g vs 3.69 ± 0.69 ng/g, P<0.05). The escape latencies of offspring rats on PND21 and PND42 in the nano-lead group were longer than those in the control group (15.54 ± 2.89 s vs 9.01 ± 4.66 s; 6.16 ± 1.42 s vs 4.26 ± 1.51 s). The numbers of platform crossings of offspring rats on PND21 and PND42 in the nano- lead group were significantly lower than those in the control group (7.77 ± 2.16 times vs 11.2 ± 1.61 times, P<0.05; 8.12 ± 1.51 times vs 13.0 ± 2.21 times, P<0.05).

ONCLUSIONn Nano-lead exposure can result in iron homeostasis disorders in the hippocampus and cortex of offspring rats and affect their learning and memory ability.

Animals ; Cerebral Cortex ; drug effects ; metabolism ; Female ; Hippocampus ; drug effects ; metabolism ; Homeostasis ; Iron ; metabolism ; Lead ; toxicity ; Learning ; drug effects ; Maternal Exposure ; adverse effects ; Memory ; drug effects ; Pregnancy ; Rats ; Rats, Sprague-Dawley

Objective: We predicted the molecular mechanism of Panax notoginseng in the treatment and improvement of scar hyperplasia, by using the methods of network pharmacology and bioinformatics. Methods: We collected of related active constituents and targets of Panax notoginseng by retrieving TCM systems pharmacology database and analysis platform (TCMSP), and collected of related active constituents and targets of scar by Genecards database and OMIM database. Cytoscape 3.6.1 software was used to construct "drugs-chemical components-targets-diseases" interaction network diagram. The protein in teraction network map (PPI) was constructed by STRING database. The key targets were used to analyze gene ontology (GO) enrichment and kyoto encyclopedia of genes and genome (KEGG) pathway enrichment. Results: Totally 7 chemical compponents, including beta-sitosterol, quercetin, Stigmasterol and etc. and 108 targets, including AKT1, JUN, MAPK1, IL6 and ect. Panax notoginseng exerts its effects on scar mainly by acting on signal pathways, including PI3K-AKt signal pathway, MAPK signal pathway, TNF signal pathway and ect. Conclusions Based on the methodology of network pharmacology, this study preliminarily predicted the major targets and pathways Panax notoginseng in the treatment of scar, providing a direction for further studies.

Objective To explore the mechanism of transforming growth factor-beta/p38 mitogen-activated protein kinases (TGF-β/P38MAPK) signaling pathway that transformed corallin into a transforming growth factor-beta/p38 mitogen activated protein kinases (TGF-β/P38MAPK).Methods The hair follicle stem cells (HFSCs) were divided into blank group,positive group and 10-10,10-9,10-8,10-7,10-6,10-5,10-4,10-3 mol/L mycoralin solution groups according to the random number table method.After 24 h,the cell proliferation rate was determined by MTT assay.The HFSCs were divided into blank group,positive group and low,medium and high dose groups according to the random number table method.The positive group was added with 5 mol/L of alkaline fibroblast growth factor solution,while the low,medium and high dose groups were added with 10-7,10-6 and 10-5 mol/L of mycoralin solution for intervention.The cell proliferation rate was determined by MTT assay.The protein expressions ofTGF-β,phosphorylated P38(p-p38),P38,Bax and bcl-2 in cells were detected by Western blot,and mRNA expressions of Bax and bcl-2 in cells of each group were detected by real-time quantitative PCR.Results Compared with the blank group,the productivity of the cells (0.418 ± 0.031,0.412 ± 0.014,0.468 ± 0.024 vs.0.353 ± 0.006) in the 10-7,10-6 and 10-5 mol/L aucubin groups significantly increased (P＜0.01).Compared with the blank group,the protein expression of TGF-β (0.377 ± 0.027,0.338 ± 0.021,0.322 ± 0.017 vs.0.557 ± 0.017),p-p38 (0.270 ± 0.020,0.228 ± 0.013,0.216 ± 0.012 vs.0.461 ± 0.012),Bax (0.450 ± 0.017,0.365 ± 0.011,0.279 ± 0.006 vs.0.551 ± 0.015) in the low,medium and high dose groups significantly down-regulated,while the Bcl-2 (0.450 ± 0.017,0.365 ± 0.011,0.279 ± 0.006 vs.0.358 ± 0.011) protein expression significantly increased.Compared with the blank group,the expression of Bcl-2 (1.714 ± 0.028,2.514 ± 0.054,3.382 ± 0.084 vs.1.000 ± 0) mRNA increased,Bax (0.415 ± 0.020,0.353 ± 0.090,0.235 ± 0.114 vs.1.000 ± 0) mRNA in the low,medium and high dose groups significantly down-regulated (P＜0.01).Conclusions By regulating the TGF-β/p38MAPK signaling pathway,mycoralin can reduce the expression of downstream apoptotic factors,and promote the repair of damaged skin.

The microbiome plays a role in the development of lower urinary tract diseases, but the impact of viruses on these conditions remains unclear. In recent years, research has emerged demonstrating a potential link between viruses and lower urinary tract diseases, including bladder cancer, prostate cancer, and overactive bladder. In this paper, the research of the correlation between viruses and lower urinary tract diseases and the related mechanisms were reviewed.

Objective:To investigate the effect and mechanism of tumor necrosis factor α (TNF-α) and its inhibitor etanercept (ETA) on the invasion ability of extravillous trophoblast in patients with unexplained recurrent spontaneous abortion (URSA).Methods:(1) Patients were collected from March to June in 2019. They were divided into the URSA group ( n=15) and the normal control group ( n=15), according to whether diagnosed with URSA or not. The mRNA expression levels of TNF-α in villi tissue of patients in the two groups were detected by quantitative real-time PCR (qRT-PCR). (2) The mRNA and protein expression levels of matrix metalloproteinase-2 (MMP-2), Slug and CXC chemokine rceptor 4 (CXCR4) in HTR-8/SVneo cells were detected by qRT-PCR or western blot after being stimulated by exogenous TNF-α (0.2, 2, 20 ng/ml) alone or TNF-α along with ETA, or phosphate buffered saline (PBS) as control. (3) The invasion ability of HTR-8/SVneo cells was investigated by transwell test after stimulating by TNF-α alone or TNF-α along with ETA. (4) The mRNA and protein expression levels of MMP-2, Slug and CXCR4 in HTR-8/SVneo cells, which were stimulated by TNF-α (2 ng/ml) alone after nuclear factor-κB (NF-κB) inhibitor, BAY 11-7028, preconditioning, were detected by qRT-PCR or western blot. Results:(1) The mRNA expression level of TNF-α in villi tissue of URSA group (4.10±0.49) was 4.1 times as much as the normal control group ( t=10.51, P<0.05). (2) The mRNA and protein expression levels of MMP-2, Slug and CXCR4 in HTR-8/SVneo cells of TNF-α group were significantly lower than those in PBS control group ( P<0.05) and those in TNF-α along with ETA group ( P<0.05). (3) The invasion ability of HTR-8/SVneo cells in TNF-α group was significantly decreased than PBS group and TNF-α along with ETA group (78±14 vs 373±26 vs 227±44, P<0.05). (4) The mRNA and protein expression levels of MMP-2, Slug and CXCR4 in HTR-8/SVneo cells with BAY 11-7028 preconditioning (mRNA: 1.03±0.10, 1.03±0.06, 1.09±0.08; protein: 1.09±0.03, 1.49±0.03, 1.12±0.03) were significantly higher than without preconditioning after being stimulated by TNF-α (all P<0.05). Conclusions:The expression of TNF-α in the villi of URSA patients is much higher than normal early pregnant women. TNF-α could decrease the capacity of invasion by suppressing the expression of MMP-2, Slug and CXCR4 through NF-κB signaling pathway in extravillous trophoblast cells. While ETA could improve the invasiveness capability of extravillous trophoblast cells through inhibiting the negative effect of TNF-α.

Preeclampsia is a kind of idiopathic disease during pregnancy. Its pathogenesis may involve many factors, such as mother, placenta and fetus. The study found that the abnormal metabolism of blood glucose and blood lipid during pregnancy may be closely related to the onset of preeclampsia. This paper reviews the research progress of abnormal glycolipid metabolism in preeclampsia at home and abroad in order to better guide the management of related aspects during pregnancy.

OBJECTIVETo analyze the efficacy and safety of laparoscopic adjustable gastric placation (LAGBP), a new procedure for surgical treatment of obesity.

METHODSClinical and 1-year follow-up data of 10 patients who underwent LAGBP in our department between September and November 2011 were analyzed retrospectively.

RESULTSThe mean operative time was (93.0±13.4) min, while the mean intraoperative blood loss was (15.5±4.7) ml. The mean excessive body weight loss rate(%EWL) at 3, 6, 9 and 12 months after the operation was 25.1%, 40.6%, 45.3% and 50.8% respectively. There were no severe post operative complications.

CONCLUSIONSLAGBP is associated with high safety and good short-term efficacy.

Body Mass Index ; Gastroplasty ; Humans ; Laparoscopy ; Obesity ; Operative Time ; Postoperative Complications ; Retrospective Studies ; Safety

Objective To explore the CT and MRI imaging and clinicopathological features of extranodal NK/T cell lymphoma (NK/TCL). Methods Sixty-six patients with NK/TCL diagnosed from 2002 June to 2016 April in Beijing Tongren Hospital with intact CT and/or MRI imaging results were enrolled in this study. All the patients had tailed clinical information and follow-up. The imaging and clinicopathological features were analyzed retrospectively and their prognostic value on overall survival was analyzed. Results There were 49 males and 17 females with median age of 42 years. The median follow-up time was 18 months. The cases showed surrounding invasions including 10 cases (15.2 %) in soft palate, 5 cases (7.6 %) in hard palate, 2 cases(3.0 %) in tonsil, 8 cases(12.1 %) in upper lip, 13 cases(19.7 %) in maxillofacial soft tissue, 9 cases (13.6 %) in eyelid, 10 cases (15.2 %) in orbital, 3 cases (4.5 %) in maxilla, 6 cases (9.1 %) in pterygopalatine fossa,6 cases(9.1 %)in infratemporal fossa,3 cases(4.5 %)in skull base, 3 cases(4.5 %) in eyeball and 2 cases (3.0 %) in brain tissue. Kaplan-Meier survival analysis found that the 2-year overall survival rates of the patients with the involvement of hard palate, upper lip, maxillofacial soft tissue, eyelid, orbital, maxillary, eyeball and brain organizer were lower than those of the patients without the involvement of these sites(χ2values were 4.470,4.041,4.456,13.933,8.986,4.000,44.121,6.527,16.822,respectively, all P< 0.05). Further multivariate Cox regression analysis showed that maxilla and brain involvement were independent adverse factors (RR=34.717, 95 % CI 3.404-354.035, P=0.003; RR=37.545, 95 % CI 3.188-442.187, P= 0.004). Conclusions MRI and CT examinations are of great value in diagnosis and prognostic assessment of NK/TCL. Clinicians can make correct and timely diagnosis by comprehensive clinical, radiological and pathological features and can make a detailed clinical assessment to give patients appropriate treatment,thus improving the outcome of the NK/TCL patients.