Objective To investigate the effect of scutellarin(STR)on the proliferation and migration of human prostate cancer cell line(PC-3)and its underlying mechanism.Methods PC-3 cells were divided into low-dose STR group,medium-dose STR group,high-dose STR group,colivelin(STAT3 activator)group,high-dose STR+colivelin group and control group.CCK-8 assay and colony formation experiments were applied to detect cell prolif-eration;Scratch experiment was applied to detect cell migration;Transmission electron microscopy was applied to observe the mitochondrial ultrastructure of PC-3 cells.The intracellular free Fe2+,malondialdehyde(MDA)content and reactive oxygen species(ROS)levels were detected by colorimetric method;RT-qPCR was applied to detect the mRNA expression of member 11 of solute vector family(SLC7A11),proliferating cell nuclear antigen(PCNA)and matrix metalloproteinase-9(MMP-9)in cells;Western blot was used to detected p-STAT3 and GPX4 proteins in cells.Results Compared to control group,the mitochondrial structure of PC-3 cells in the low-dose STR group,medium-dose STR group and high-dose STR group was significantly disrupted.The A450 value,colony formation rate,scratch healing rate,PCNA,SLC7A11,MMP-9 mRNA expression,and p-STAT3,GPX4 protein all reduced.While Fe2+,MDA content,and that ROS level increased with dose-dependent way(P＜0.05).Compared with control group,the destruction of mitochondrial structure in cells from colivelin group improved;The A450 value,colony formation rate,scratch healing rate,PCNA,SLC7A11,MMP-9 mRNA expression and p-STAT3,GPX4 protein all increased,while Fe2+MDA content,and ROS level decreased(P＜0.05).Compared with high-dose STR group,the damage of mitochondrial structure in PC-3 cells in the high-dose STR+colivelin group was re-duced.The A450 value,colony formation rate,scratch healing rate,PCNA,SLC7A11,MMP-9 mRNA expression,and p-STAT3,GPX4 protein increased,while Fe2+,MDA content and ROS level decreased(P＜0.05).Conclusions The mechanism by of STR reducing proliferation and migration of prostate cancer cells is potentially related to the inhibition of STAT3/GPX4 pathway.

Objective:To analyze risk factors for prognosis of adult patients with traumatic brain injury (TBI), construct the prognostic model of TBI and evaluate its predictive value.Methods:A case-control study was used to analyze the clinical data of 522 patients with TBI admitted to Xijing Hospital of Air Force Medical University from March 2011 to September 2019, including 438 males and 84 females; aged 18-75 years [(44.9±15.0)years]. According to the Glasgow outcome score (GOS) at discharge, the patients were divided into good prognosis group (GOS 4-5 points, n=165) and poor prognosis group (GOS 1-3 points, n=357). The two groups were compared with regards to qualitative data such as sex, underlying diseases, causes of injury, multiple injuries, open injuries, intracranial foreign bodies, cerebral herniation, consciousness status on admission and at discharge, surgery, lung infection on admission, tracheostomy, ventilator-assisted ventilation, hospital-acquired pneumonia/pathogenic bacteria and intracranial infection, and quantitative data such as Glasgow coma score (GCS) on admission and at discharge, age, measurements on admission [systolic blood pressure, diastolic blood pressure, mean arterial pressure, temperature, heart rate, creatinine, urea nitrogen, blood sodium, blood potassium, blood glucose, prothrombin time (PT), activated partial thromboplastin time (APTT), platelets, international normalized ratio (INR), pupil size of both eyes] and length of hospital stay. Univariate analysis and Lasso regression analysis were used to screen the risk factors affecting the prognosis of TBI patients, and the selected influencing factors were included in multivariate Logistic regression analysis to identify independent risk factors and construct regression equations. R was used to draw a visual nomogram based on regression equation for predicting the prognosis of TBI patients. The prognostic predictive value of the nomogram was evaluated by using the receiver operating characteristic (ROC) curve, and the area under the curve (AUC), Youden index, sensitivity, specificity and consistency index (C index) were calculated. Results:Univariate analysis showed that there were significant differences between the two groups in underlying diseases, open injuries, cerebral herniation, consciousness status on admission and at discharge, lung infection on admission, tracheostomy, ventilator-assisted ventilation, hospital-acquired pneumonia/pathogenic bacteria, GCS on admission and at discharge, age, and measurements on admission (systolic blood pressure, mean arterial pressure, body temperature, heart rate, creatinine, urea nitrogen, blood potassium, blood glucose, PT, INR, pupil size of right eye) (all P<0.05 or 0.01). There were no significant differences between the two groups in gender, causes of injury, multiple injuries, intracranial foreign bodies, surgery, intracranial infection, measurements on admission (diastolic blood pressure, blood sodium, APTT, platelets, pupil size of left eye) and length of hospital stay (all P>0.05). After screening by Lasso regression model, the results of multivariate Logistic regression analysis showed that GCS on admission ( OR=0.67, 95% CI 0.62, 0.73, P<0.01), age ( OR=1.03, 95% CI 1.01, 1.04, P<0.01), blood glucose on admission ( OR=1.17, 95% CI 1.06, 1.30, P<0.01) and INR on admission ( OR=17.08, 95% CI 2.12, 137.89, P<0.01) could be used as the main risk factors to construct the prediction model, and the regression equation was constructed: Logit [ P/(1- P)]=-0.398× "GCS on admission"+0.024× "age"+0.158×"blood glucose on admission"+2.838×"INR on admission"-1.693. The AUC for the prognosis prediction in adult patients with TBI using R based on a visual nomogram model was 0.87 (95% CI 0.83, 0.89, P<0.01). The Youden index for the predicted probability was 0.60 (sensitivity of 85.2% and specificity of 75.2%), with the C index of 0.87. Conclusion:Age, GCS on admission, blood glucose on admission and INR on admission are the main risk factors affecting the prognosis of TBI in adults, and the nomogram drawn by these parameters can better predict their clinical outcome.

Endothelial cells that form the inner layers of both blood and lymphatic vessels are important components of the vascular system and are involved in the pathogenesis of vascular and lymphatic diseases. Angiopoietin (Ang)-Tie axis in endothelial cells is the second endothelium-specific ligand-receptor signaling system necessary for embryonic cardiovascular and lymphatic development in addition to the vascular endothelial growth factor receptor pathway. The Ang-Tie axis also maintains vascular homeostasis by regulating postnatal angiogenesis, vessel remodeling, vascular permeability, and inflammation. Therefore, the dysfunction of this system leads to many vascular and lymphatic diseases. In light of the recent advances on the role of the Ang-Tie axis in vascular and lymphatic system-related diseases, this review summarizes the functions of the Ang-Tie axis in inflammation-induced vascular permeability, vascular remodeling, ocular angiogenesis, shear stress response, atherosclerosis, tumor angiogenesis, and metastasis. Moreover, this review summarizes the relevant therapeutic antibodies, recombinant proteins, and small molecular drugs associated with the Ang-Tie axis.
Angiopoietins ; Endothelial Cells/metabolism* ; Humans ; Lymphatic Diseases ; Lymphatic System/metabolism* ; Receptor, TIE-2/metabolism* ; Signal Transduction ; Vascular Endothelial Growth Factor A

Ischemic stroke is a major health crisis causing high mortality and morbidity. The key treatment relies on the rapid intervention to dissolve thrombus, to reduce bleeding side effect and re-canalize clotted blood vessels using clot lysis drugs. Tissue plasminogen activator (tPA) is the only FDA-approved drug for ischemic stroke, but it has many limitations in clinical use. In recent years, the development of thrombolytic drugs and treatment strategies based on tPA has been progressed rapidly. Here we review the recent progress in this field, including the contributions from us and others, to promote the future development of novel thrombolytic drugs.
Brain Ischemia/drug therapy* ; Fibrinolytic Agents/therapeutic use* ; Humans ; Research/trends* ; Stroke/drug therapy* ; Thrombolytic Therapy/trends* ; Tissue Plasminogen Activator/therapeutic use*

BACKGROUND: Neuropeptides, a kind of endogenous active substance in nerve tissues, can modulate physiological functions of multiple body systems.OBJECTIVE: To observe the effects of vascular bundles or sensory nerve tracts implanted into tissue-engineered bone for rabbit large bone defects on the expression levels of calcitonin gene-related peptide (CGRP) and neuropeptide-Y.METHODS: Fifty-four New Zealand rabbits were enrolled to make model of large bone defects, and then, the animal models were randomly divided into three groups, including sensory nerve tract, vascular bundle, and control groups (n=18 per group), followed by implanted with sensory nerve tracts, vascular bundle, and tissue-engineered bone without sensory tracts or vascular bundle, respectively. The defected bone received gross and Masson staining at 4, 8 and 12 weeks after modeling, to compare the expression levels of CGRP and neuropeptide-Y in each group.RESULTS AND CONCLUSION: mRNA expression levels of CGRP and neuropeptide-Y in the sensory nerve tract and vascular bundle groups were significantly higher than those in the control group at different time points after modeling (P < 0.05). mRNA expression levels of CGRP and neuropeptide-Y in the tissue-engineered bone began to be increased and peaked at the 8th week, and then decreased (P < 0.05), which were the lowest at the 4th week (P < 0.05).Immunohistochemical staining results showed that CGRP was mainly found in the bridge, periosteum of newly born bones and around blood vessels; while neuropeptide-Y mainly localized in the medullary cavity and around blood vessels. These results indicate that the implantation of vascular bundle and sensory nerve tracts for bone defects can upregulate the expression levels of CGRP and neuropeptide-Y, and promote bone repair. However, sensory tract implantation may cause sensory impairment; thereafter, vascular bundle implantation is more suitable for ideal tissue-engineered construction to meet physical requirements.

Objective To determine the feasibility and safety of transprostatic utricle seminal vesiculoscopy in the treatment of hemospermia. Methods Totally 11 patients with hemospermia, mean age of (46.6 ± 3.5) years, ranging from 38 to 68 years, for 3 months admitted from September 2012 to August 2015 were enrolled, Their main manifestations were hemospermia. Painful ejaculation was observed in 7 patients, and perineal and testicular pain occured in 4 patients. They all underwent transprostatic utricle seminal vesiculoscopy, and then were followed up for 3 to 6 months. Results Ten patients were operated successfully, but 1 patient failed. The operation revealed that the causes of hemospermia were seminal vesiculitis in 8 cases, seminal vesiculitis accompanied with seminal calculi in 2 cases, and ejaculatory duct cyst in 1 case. Operation time was (29.2 ± 3.2) min ( ranging from 25 to 37 min) , and hospital stay was 2 d ( from 2 to 4 d). Hemospermia disappeared in 10 patients within 1 month of surgery, and hemospermia recurrence was observed in 1 patient within 6 months. The patient was treated with transprostatic utricle Holmium laser incision, then hemospermia was dispeared,Two cases of postoperative epididymitis were cured after one week of antibiotic treatment. Conclusions Seminal vesiculoscopy is a safe and effective to treat hemaospermia.

OBJECTIVETo understand the molecular characteristics of a dengue virus outbreak in China-Myanmar border region, Yunnan province, 2015 and provide etiological evidence for the disease control and prevention.

METHODSSemi-nested RTPCR was conducted to detect the capsid premembrane (CprM) gene of RNA of dengue virus by using dengue virus NS1 positive serum samples collected in Mengdin township, Gengma county, Yunnan province in July, 2015. Some positive samples were then detected by using PCR with specific primers to amplify the full E gene. The positive PCR products were directly sequenced. Then sequences generated in this study were BLAST in NCBI website and aligned in Megalign in DNAstar program. Multiple sequence alignments were carried out by using Mega 5.05 software based on the sequences generated in this study and sequences downloaded from GenBank, including the representative strains from different countries and regions. Phylogenetic trees were constructed by using Neighbor-Joining tree methods with Mega 5.05 software.

RESULTSTwenty one of 25 local cases and 10 of 14 imported cases from Myanmar were positive for DENV-1. Eight serum samples were negative for dengue virus. A total of 13 strains with E gene (1485 bp), including 8 local strains and 5 imported strains, were sequenced, which shared 100% nucleotide sequence identities. Twelve strains with CprM gene (406 bp) from 9 local cases and 3 imported cases shared 100% nucleotide sequence identities. Phylogenetic analyses based on E gene showed that the new 13 strains clustered in genotype I of dengue virus and formed a distinct lineage.

CONCLUSIONSThis outbreak was caused by genotype I of DENV-1, which had the closest phylogenetic relationships with dengue virus from neighboring Burma area. Comprehensive measures of prevention and control of dengue fever should be strengthened to prevent the spread of dengue virus.

Capsid Proteins ; China ; epidemiology ; DNA Primers ; Databases, Nucleic Acid ; Dengue ; epidemiology ; virology ; Dengue Virus ; genetics ; Disease Outbreaks ; Genotype ; Humans ; Myanmar ; epidemiology ; Phylogeny ; Polymerase Chain Reaction ; Sequence Alignment ; Software

Objective To investigate the clinical feature , pathologic characteristics and prognosis of urothelial carcinoma of bladder with squamous differentiation . Methods From Jan.2010 to Jun.2013, the pathological and clinical data of 96 cases of urothelial carcinoma of bladder with or without squamous dif-ferentiation were compared .Of the group with squamous differentiation , there were 39 males and 9 females with a median age of 70 (29 to 87) years.44 cases presented with painless gross hematuria .4 cases presen-ted with finding of bladder tumors in annual physical examination .TURBT, partial cystectomy and radical cystectomy were performed in 25, 8 and 13 cases, respectively.In addition, one case was only underwent bi-lateral ureteral skin gastrostomy .The last one only performed cystoscopy .In accordance with sex , age, path-ological stage and classification and surgical approach , 48 controls were selected .For the other group , there were 40 males and 8 females with a median age of 68 (39 to 86) years.45 cases presented with painless gross hematuria.3 cases presented with finding bladder tumors by annual physical examination .TURBT, par-tial cystectomy and radical cystectomy were performed in 28, 7 and 13 cases, respectively.All patients with retaining bladder had postoperative intravesical instillation for one year .Some patients with or without bladder performed 3-6 cycles chemotherapy with the GC protocol . Results In squamous differentiation group , there were 1 (2.1%) pTa, 25 (52.1%) pT1, 17 (35.4%) pT2, 4 (8.3%) pT3 and 1 (2.1%) pT4 tumors. Whereas, 1 (2.1%) pTa, 28 (58.3%) pT1, 16 (33.3%) pT2, 2 (4.2%) pT3 and 1 (2.1%)pT4 tumors were selected in the control group .There were 2 (4.2%) cases with low grade and 46 (95.8%) cases with high grade carcinomain in both groups .Patients were followed up with a mean duration of 16 and 12 months in squamous differentiation and control group , respectively .In squamous differentiation group , eight recur-rences were recorded with a mean follow-up of 12 months.Of the 3 died patients, only one died from bladder cancer.In control group, seven recurrences were recorded with a mean follow-up of 22 months, and no pa-tient died.For patients with TURBT, 3 year recurrence rate of patients with squamous differentiation was 49.5%, while the control was 34.8%.The difference was statistically significant (P<0.05). Conclusions Urothelial carcinoma of bladder with squamous differentiation is at a high level of malignant and recurrence . The rate of myometrial invasion with squamous differentiation is higher than pure urothelial bladder cancer . Patients with squamous differentiation should be closely followed up .

Objective To explore whether the respective implantation of vascular bundles and sensory nerve tracts into a tissue-engineered bone will affect the expression of CGRP (Calcitonin gene related peptide) and its receptor. Methods Fifty-four New Zealand rabbits were randomly divided into 3 even groups for implantation of sensory nerve tracts (group A),implantation of vascular bundles (group B),and a control group of simple tissue-engineered bone (group C) . Animals were sacrificed 4,8,12 weeks after implantation,respectively. Masson staining was conducted to observe the process of bone formation and re-molding. CGRP and CGRPR-1 expressions in the new bone were measured by immunohistochemistry and Real-time PCR at 4,8 and 12 weeks after implantation. Results At all time points,the CGRP and CGRPR-1 expressions in groups A and B were significantly higher than in group C (P<0.05),and those in group A were higher than in group B too (P<0.05) . Over time,the expressions of CGRP and CGRPR-1 mRNA in each group in the new bone tissue were gradually reduced after an initial increase. The neuropeptide expression at the 8th week was higher than those at the 4th and 12th weeks. The neuropeptide expression at the 4th week was the lowest. The expression of CGRP was mainly localized in the periphery of newly generated bone,periosteum and the blood vessels. The expression of CGRPR-1 was mainly localized in the periphery of osteoblasts. Conclusions Implantation of either vascular bundles or sensory nerve tracts can promote neuropeptide secretion. The vascular bundle implantation may result in higher expressions of CGRP and CGRPR-1 than sensory nerve tract implantation.

The mollusicidal effect and toxicity to fish with META-Li in field were tested in mountain areas in Zhejiang Province. The snail control test, which had 3 groups including a META-Li group, niclosamide group and control group, were performed by the spraying method. The adjusted mortalities of snails in the META-Li group on the 3rd, 7th and 15th day were 89.76% , 87.98% and 94.10% , respectively, in the niclosamide group were 89.70% , 83.22% and 94.72% , respectively .and there was no significant difference between the two groups ( P > 0.05), but they were decreased obviously compared with the control group, which were 9.24% , 9.50% and 15.21% , respectively(P <0.05). The toxicity test to fish with META-Li included 3 groups, namely a high concentration META-Li group, low concentration META-Li group and control group, and none fish was dead. It is suggested META-Li has low toxicity to fish, and is suitable to snail control in aquiculture areas.