Bloodstream infections are featured by acute onset, rapid progression and high mortality. Early identification and accurate prognostic assessment are crucial for improving patient outcomes. This article reviews five novel biomarkers in assessing the severity and prognosis of patients with acute bloodstream infection, namely soluble triggering receptor expressed on myeloid cell-1, soluble form of the urokinase plasminogen activator receptor, presepsin, heparin-binding protein and microRNAs, all of which are positively correlated with the severity of patients’ condition, and some perform better than traditional biomarkers. However, they still have limitations such as inadequate specificity or sensitivity and lack of large-scale verification. In the future, it is necessary to integrate molecular detection and artificial intelligence to optimize application strategies and provide personalized diagnosis and treatment.
Objective Investigate the effect and treatment prospects of urokinase-type plasminogen activator receptor（uPAR）in human epidermal growth factor receptor-2 （HER-2） positive breast cancer. Method Aricals related effect of uPAR in HER-2 positive breast caner were retrieved through Pubmed， and the role of uPAR was reviewed. Results uPAR played a very important role in the HER-2 positive breast cancer， anti-uPAR monomer or uPAR binding inhibitors could inhibit the growth， invasion and metastasis of breast cancer cells. Conclusion uPAR is one of the effective target for breast cancer， and it provides a new breakthrough in the treatment of HER-2 positive breast cancer.
Urokinase plasminogen activator receptor (uPAR) is a membrane protein which is attached to the cellular external membrane. The uPAR expression can be observed both in tumor cells and in tumor-associated stromal cells. Thus, in the present study, the human amino-terminal fragment (hATF), as a targeting element to uPAR, is used to conjugate to the surface of superparamagnetic iron nanoparticle (SPIO). Flowcytometry was used to examine the uPAR expression in different tumor cell lines. The specificity of hATF-SPIO was verified by Prussian blue stain and cell phantom test. The imaging properties of hATF-SPIO were confirmed in vivo magnetic resonance imaging (MRI) of uPAR-elevated colon tumor. Finally, the distribution of hATF-SPIO in tumor tissue was confirmed by pathological staining. Results showed that the three cells in which we screened, presented different expression characteristics, i.e., Hela cells strongly expressed uPAR, HT29 cells moderately expressed uPAR, but Lovo cells didn't express uPAR. In vitro, after incubating with Hela cells, hATF-SPIO could specifically combined to and be subsequently internalized by uPAR positive cells, which could be observed via Prussian blue staining. Meanwhile T2WI signal intensity of Hela cells, after incubation with targeted probe, significantly decreased, and otherwise no obvious changes in Lovo cells both by Prussian blue staining and MRI scans. In vivo, hATF-SPIO could be systematically delivered to HT29 xenograft and accumulated in the tumor tissue which was confirmed by Prussian Blue stain compared to Lovo xenografts. Twenty-four hours after injection of targeting probe, the signal intensity of HT29 xenografts was lower than Lovo ones which was statistically significant. This targeting nanoparticles enabled not only in vitro specifically combining to uPAR positive cells but also in vivo imaging of uPAR moderately elevated colon cancer lesions.
Abstract: Objective To investigate the messenger ribonucleic acid (mRNA) expression level of tissue-type plasminogen activator (t-PA) in endothelial cells derived from adult mesenchymal stem cells (MSCs) after fluid shear stress loading which is within the physiological range. Methods After culturing in vitro, bone marrow MSCs of SD rats were seeded on slides.When it come to 80% confluence,26 slides were exposed to 5dyn/cm2 fluid shear stress for 3h in a flow chamber, and then induced to endothelial cells. Among them,13 slides constituted group Ⅰ, and the rest 13 slides set up group Ⅱ, which would be cultured for 3-4d further and passaged in 1∶3. At the same time, control group was set up, which including the cells never exposed to fluid shear stress before the endothelial differentiation. Fluid shear stress were exerting to cells in a specially made flow chamber. The expression level of t-PA mRNA of all groups were measured by real-time fluorescent quantitation reverse transcriptionpolymerase chain reaction (RTPCR). Results After endothelial differentiation for 7 days, the SD rats bone marrow MSCs acquired typical endothelial cell appearance. The t-PA mRNA expression level of group Ⅰ and group Ⅱ have an obviously enhance compared with control group(P＜0.05). The t-PA mRNA expression level of group Ⅱ step down a little (P＞0.05), but it is still significantly higher than that of control group (P＜0.05). Conclusion Fluid shear stress could provide a protective action on the endothelial cells induced from MSCs in vitro, and the effect maintains with the cells passages. This formulates a theoretical foundation to the therapeutics of atherosclerosis and selection of seed cells in vascular tissue engineering.
Objective To investigate the expression of urokinase-type plasminogen activator (uPA) mRNA in gastric cancer tissues and cancer-adjacent tissues and the relationship between its expression and biologic behavior of tumor. Methods Fourty-eight cases with gastric cancer were detected for the expression of uPA mRNA by fluorogenic probe quantitative reverse transcription polymerase chain reaction (RTPCR). Results The positive expression rate of uPA mRNA was 83.3%, 25.0%, 93.8% and 62.5% in gastric cancer tissues,cancer-adjacent tissues, gastric cancer tissues with lymph node metastasis and with non-lymph node metastasis respectively. Expression of uPA mRNA was positively related with the invasion depth of gastric cancer. Conclusion Expression of uPA mRNA is significantly increased in gastric cancer and it can be used as an indicator to judge the metastasis and prognosis of tumor.
【Abstract】ObjectiveTo investigate the relationship between the expression of urokinase-type plasminogen activator (uPA) mRNA and breast cancer, lymph node metastasis. MethodsSixty patients with breast tumor were selected randomly and the expression of uPA mRNA was detected with RT-PCR. The patients were divided into benign group (18 cases) and malignant group (42 cases) which included 22 cases with lymph node metastasis and 20 cases without lymph node metastasis. The relationship between uPA mRNA expression and breast cancer, lymph node metastasis was analyzed. ResultsAmong these 18 benign tumors, low expression of uPA mRNA was found in 2 cases and the others were negative. While in 42 cases of malignant tumor, uPA mRNA were positive in 22 cases of lymph node metastasis, 16 of which were high expression, 5 of which were moderate expression, and 1 was low expression. uPA mRNA were positive in 18 of 20 cases of nonmetastatic lymph node, 1 of which was high expression, 5 of which were moderate expression and 12 of which were low expression, the other 2 were negative expression. The expression of uPA mRNA had significant difference between benign and malignant tumors (P＜0.05). The expression in lymph node metastasis was much higher than no lymph node metastasis (P＜0.05). ConclusionThe expression of uPA mRNA in malignant breast cancer is obviously higher than that in benign breast tumor. The expression tensity of uPA is highly relevant to lymph node metastasis in malignant breast cancer, which can provide evidence for clinical staging and therapy.
ObjectiveTo explore the clinical value of the soluble urokinase type plasminogen activator receptor (suPAR) level in bronchoalveolar lavage fluid (BALF) for evaluateting the disease severity and prognosis of severe community-acquired pneumonia (SCAP). MethodsEighty-four patients with SCAP were recruited as a SCAP group from the respiratory department, ICU and RICU between April 2014 and April 2016. According to their organ dysfunction, the SCAP patients were subdivided into a MODS group and a non-MODS group. Depending on the treatment response on the 7th day of treatment, they were subdivided into an effective group and an ineffective group. According to the survival condition within 28 days, they were subdivided into a survival group and a death group. Meanwhile, 50 cases with non-severe common community acquired pneumonia were recruited as a control group. On the admission day, all cases were evaluated by PSI score and APACHE Ⅱscore. The serum suPAR level were detected by ELISA on the 1st day in hospital. The suPAR and procalcitonin (PCT) levels in the patient's BALF and serum were detected on the 1st, 3rd, 7th day, discharge or death day. The symptoms and signs, biochemical and pulmonary imaging changes were also observed. ResultsThere were no differences in the sex, age, body weight, duration of pneumonia, or complicated diseases such as hypertension, coronary heart disease and cerebral vascular diseases between the SCAP group and the control group (all P > 0.05). The suPAR levels in serum and BALF of the SCAP group were higher than those of the control group with significant differences (all P < 0.05). The suPAR level in BALF was obviously higher than that in serum in the SCAP group with significant difference (P < 0.05), and slightly higher than that in serum in the control group with no significant difference (P > 0.05). The level of suPAR in BALF of the MODS group was significantly higher than that in the non-MODS group with significant difference (P < 0.05), but there was no significant difference in the PCT level between the two groups (P > 0.05). The suPAR level in the ineffective treatment group was significantly higher than that in the effective treatment group on the 7th day in hospital with significant difference (P < 0.05). The suPAR levels in BALF of the death group were higher than those in the survival group at each time point after admittion with significant difference (all P < 0.05), and the PCT levels had no significant difference between the two groups within 1 week of each time point (all P > 0.05). The suPAR level in BALF of the SCAP group was positively correlated with APACHEⅡ score and PSI score (r=0.578, P=0.0085; r=0.565, P=0.0071), and plasma PCT level was weakly correlated with the APACHEⅡ score and PSI score (r1=-0.0137, r2=-0.0152). ConclusionThe SuPAR level in BALF of patients with SCAP is closely related to the severity and prognosis, and can be used as an index to assess the severity and prognosis.
ObjectiveTo observe the clinical effect of intravitreal injection of tissue plasminogen activator (t-PA), ranibizumab and C3F8 in the treatment of early submacular hemorrhage (SMH) induce to polypoid choroidal vasculopathy (PCV).MethodsThe clinical data of 20 eyes of 20 patients with early SMH induce to PCV were enrolled in this study. The duration of bleeding in the eye was 7 to 28 days, and the mean duration of bleeding was 14.8±5.6 days. All eyes are measured using the Snellen chart best corrected visual acuity (BCVA), logarithm of the minimum angle of resolution (logMAR) was used to calculate visual acuity. Measure central retinal thickness (CRT) and central retinal pigment epithelial detachment (PED) thickness using frequency-domain optical coherence tomography. The average logMAR BCVA of eyes was 1.73±0.91; the mean CRT was 620.0±275.8 μm; the average central PED thickness was 720.3±261.9 μm. All eyes receive intravitreal injection of t-PA, ranibizumab and C3F8. The intravitreal injection of ranibizumab was administered once a month for 3 consecutive months, followed by an on-demand treatment plan. Mean follow-up time was 9.9±3.6 months. The changes in BCVA, CRT, central PED thickness and clearance degree of SMH at 6 months after treatment were observed.ResultsOn the 6 months after treatment, the average logMAR BCVA, CRT and central PED thickness of the eyes were respectively 0.42±0.37, 290.2±97.4 μm and 41.6±78.1 μm. Compared with baseline, the after treatment BCVA was significantly increased (F=38.14, P=0.000), but the CRT and central PED were significantly decreased (F=7.48, 75.94; P=0.000, 0.000). Among the 20 eyes, 16 eyes of SMH was completely cleared, accounting for 80%;4 eyes was partially cleared, accounting for 20%. No recurrence and systemic or local complications occurred during follow-up of all eyes.ConclusionIntravitreal injection of t-PA, ranibizumab, and C3F8 in the treatment of early SMH induce to PCV can effectively remove SMH, improve vision, reduce CRT and central thickness of PED.
ObjectiveTo observe the efficacy and safety of vitrectomy combined with submacular injection of tissue-type plasminogen activator (t-PA), gas filling and anti-VEGF drugs (multiple therapy) for thick submacular hemorrhage.MethodsA retrospective case study. From January 2014 to June 2018, 24 patients (24 eyes) with thick submacular hemorrhage who received multiple therapy at the Department of Ophthalmology of Peking University Third Hospital were included in the study. Among them, there were 15 males and 9 females with the average age of 69.05±8.86 years. The average submacular bleeding time was 17.15±10.30 days, the average bleeding area was 13.85±8.63 DD. Seventeen eyes showed hemorrhagic RPE detachment. The international standard visual acuity chart was used to BCVA examination, which was converted to logMAR visual acuity in statistics. The frequency domain OCT was used to measure the height of the foveal elevation. The average logMAR BCVA of the affected eye was 1.37±0.38. The average height of the macular fovea was 824.94±294.38 μm. All eyes underwent 23G or 25G vitrectomy. During the operation, 0.1-0.5 ml t-PA (10 μg/0.1 ml) was injected under the macula. The vitreous cavity was filled with 15% C3F8 after gas-liquid exchange in 13 eyes, and 11 eyes were filled with sterilized air. Eleven eyes were injected with anti-VEGF drugs at the end of the operation, and anti-VEGF drugs were given PRN treatment according to the activity of the lesion. The average follow-up time after treatment was 27.90±22.21 months. The absorption of bleeding under the macula, the improvement of vision, the occurrence of rebleeding and treatment-related complications were observed and recorded. The Wilcoxon rank sum test was performed to compare the BCVA and the height of foveal elevation before and after treatment.ResultsOne month after the treatment, the blood in the fovea of all affected eyes was cleared. At the last follow-up, the logMAR BCVA and macular foveal elevation were 0.82±0.28 and 253.88±71.75 μm, respectively. Compared with those before treatment, the difference was statistically significant (Z=－3.727, －3.234; P＜0.001, ＜0.001). The average intravitreal injection of anti-VEGF drugs was 1.08 times. During the operation, a tiny hole was formed in the center of the macula when t-PA was injected under the retina. Two eyes showed mild vitreous hemorrhage early after the operation. During the follow-up period, bleeding recurred in 2 eyes.ConclusionsVitrectomy combined with submacular injection of t-PA, gas filling, and anti-VEGF drugs is an optimal combination for the treatment of thick submacular hemorrhage. It can effectively remove submacular hemorrhage, improve vision, reduce foveal elevation with good safety.
ObjectiveTo investigate the therapeutic effect of kinetin on bleomycin A5 (BLM-A5)-induced pulmonary fibrosis in rats. MethodsSixty female Wistar rats were randomly divided into three groups. Group A (n=20) was intratracheally injected with saline as control. Group B (n=20) were intratracheally injected with BLM-A5 to establish pulmonary fibrosis model. Group C (n=20) was intratracheally injected with BLM-A5 and received intraperitoneal injection of kinetin at 0.5 mL/100 g once daily. The rats were sacrificed on the 3rd,7th,14th and 28th day respectively. HE and Masson staining were performed to observe lung pathological changes. The contents of hydroxyproline (HYP),urokinase-type plasminogen activator (u-PA),tissue-type plasminogen activator (t-PA),and PAI-1 in lung and plasma were measured by ELISA. ResultsAlveolitis was most obvious on the 7th day and pulmonary fibrosis was most severe on the 28th day in group B compared with other two groups (P<0.05). Alveolitis and pulmonary fibrosis in group C were significantly alleviated compared with group B (P<0.05),but still more severe than group A (P<0.05). The HYP contents in group B,coincided with fibrosis,began to increase on the 7th day and reached the peak on the 28th day,significantly higher than those in other two groups (P<0.05). The u-PA contents of lung tissue in group B began to decline on the 3rd day,reached the minimum on the 7th day,and was still significantly lower than those in other two groups (P<0.05).On the 14th day, the u-PA contents had no significant difference among three groups. The u-PA plasma contents in group B began to decline on the 3rd day,reached the minimum and had significant difference compared with other two groups on the 7th day (P<0.05),and there was no significantly difference among three groups after the 14th day. The t-PA contents change of lung tissue and plasma in three groups were generally consistent with u-PA,but the t-PA plasma contents in group B were still significantly lower than those in group A on the 14th day (P<0.05). The PAI-1 contents of lung tissue in group B began to increase on the 3rd day,reached the maximum on the 7th day,was still significantly higher than those in other two groups (P<0.05),and there was no significant difference among three groups on the 14th day. The PAI-1 contents in group C decreased compared with those in group B (P<0.05),but still higher than those in group A (P<0.05),and there was no difference among them on the 14th day. The PAI-1 plasma contents in group B began to increase on the 3rd day,reached the maximum and was significantly higher than other two groups on the 7th day (P<0.05),and there was no significant difference among three groups on the 14th day. ConclusionThe contents of u-PA and t-PA are increased by inhibiting PAI-1 generation in lung tissue through kinetin treatment,so that,kinetin can suppress pulmonary fibrosis induced by BLM-A5.