The association of the systemic immune-inflammation index and stent thrombosis in myocardial infarction patients after coronary stent implantation-a retrospectively study.

Background: A small number of patients can develop stent thrombosis after coronary stent implantation. Diabetes, malignant tumors, anemia, etc. have been identified as risk factors for stent thrombosis. A previous study confirmed that the systemic immune-inflammatory index is associated with venous thrombosis. However, there are no studies investigating the association between the systemic immune-inflammation index and stent thrombosis after coronary stent implantation, and thus, we designed this study. Methods: A total of 887 myocardial infarction patients admitted to the Wuhan University Hospital from January 2019 to June 2021 were included. All of the patients received coronary stent implantation and were followed up for 1 year by clinic visit. The patients were divided into a stent thrombosis group (n=27) and a control group (n=860) according to whether or not they suffered stent thrombosis. The clinical features of the two groups were observed, and the receiver operator characteristic (ROC) curve was used to analyze the predictive value of the systemic immune-inflammation index for stent thrombosis in patients with myocardial infarction after coronary artery stenting. Results: Compared with the control group, the proportion of stent number ≥4 in the stent thrombosis group was significantly higher (62.96% vs. 38.72%, P=0.011), and the proportion of patients with a systemic immune-inflammation index ≥636 was markedly increased (55.56% vs. 23.26%, P=0.000). The number of stents and the systemic immune-inflammation index were both valuable in predicting stent thrombosis, and the predictive value of the systemic immune-inflammation index was higher, with an area under the curve of 0.736 (95% confidence interval: 0.647-0.824, P=0.000), the best diagnostic value was 636, and the sensitivity and specificity were 0.556 and 0.767. The systemic immune-inflammation index ≥636 and the number of stents ≥4 were independent risk factors for stent thrombosis after coronary stent implantation (P<0.05). Compared with the control group, the incidence of recurrent myocardial infarction was notably increased in the stent thrombosis group (33.33% vs. 3.26%, P=0.000), and mortality was significantly higher in the stent thrombosis group (14.81% vs. 0.93%, P=0.000). Conclusions: The systemic immune-inflammation index was associated with the development of stent thrombosis in patients with myocardial infarction after coronary stent implantation.

Prediction of Blood Glucose Concentration Based on CEEMD and Improved Particle Swarm Optimization LSSVM.

Aiming at the difficulty of accurate prediction due to the randomness and nonstationary nature of blood glucose concentration series, a blood glucose concentration prediction model based on complementary ensemble empirical mode decomposition (CEEMD) and least squares support vector machine (LSSVM) is proposed. Firstly, CEEMD is used to convert the blood glucose concentration sequence into a series of intrinsic mode functions (IMFs) to reduce the impact of randomness and nonstationary signals on prediction performance. Then, a LSSVM prediction model is established for each mode IMF. The comprehensive learning particle swarm optimization (CLPSO) algorithm is used to optimize the kernel parameters of LSSVM. Finally, the prediction results of all IMFs are superimposed to yield the final blood glucose concentration prediction value. The experimental results show that the proposed prediction model has higher prediction accuracy in short-term blood glucose concentration values.

Preliminary evaluation of the efficacy and safety of brimonidine for general anesthesia.

BACKGROUND: To determine the hypnotic and analgesic effects of brimonidine, and evaluate its efficacy and safety for general anesthesia. Potentiation of pentobarbital sleeping time following brimonidine administration was observed in mice, as was the analgesic activity of brimonidine. METHODS: The median effective dose (ED50) and lethal dose (LD50) of intraperitoneally injected brimonidine were determined in hypnotized mice. In addition, the LD50 of intravenously injected brimonidine, and ED50 of intravenously, intramuscularly, and intrarectally injected brimonidine in hypnotized rabbits were determined. Finally, the synergistic anesthetic effect of brimonidine and chloral hydrate was evaluated in rabbits. RESULTS: Intraperitoneal injection of 10 mg/kg brimonidine enhanced the hypnotic effect of a threshold dose of pentobarbital. Intraperitoneally injected brimonidine produced dose-related analgesic effects in mice. The ED50 of intraperitoneally administered brimonidine in hypnotized mice was 75.7 mg/kg and the LD50 was 379 mg/kg. ED50 values of intravenous, intramuscular, and intrarectal brimonidine for hypnosis in rabbits were 5.2 mg/kg, 8.8 mg/kg, and 8.7 mg/kg, respectively; the LD50 of intravenous brimonidine was 146 mg/kg. Combined intravenous administration of 0.6 mg/kg brimonidine and 0.03 g/kg chloral hydrate had a synergistic anesthetic effect. CONCLUSIONS: Brimonidine elicited hypnotic and analgesic effects after systemic administration and exhibited safety. Moreover, brimonidine enhanced the effects of other types of narcotics when combined.

[Cloning and expression analysis of CpPMM gene in Codonopsis pilosula].

GDP-mannose is an important precursor for the synthesis of Codonopsis pilosula polysaccharides and involved in the synthesis of sugar chains. Phosphomannomutase(PMM)catalyzes the conversion of mannose-6-phosphate(Man-6-P)to mannose-1-phosphate(Man-1-P)to synthesize GDP-mannose. In this study, specific primers were designed based on the PMM gene sequence information in transcriptome data, and the full length of the C. pilosula PMM gene was cloned and named CpPMM. The correlation between the CpPMM gene expression and C. pilosula polysaccharide synthesis was analyzed by a series of bioinformatics analysis, prokaryotic expression and qRT-PCR. The results show that the CpPMM gene contains a 741 bp open reading frame(ORF), encoding 246 amino acids, which is highly similar to the PMM of other species and highly homologous to the Helianthus annuus from the Asteraceae family. It was predicted to be a hydrophilic non-transmembrane protein without signal peptide, which was predicted to be located in the cytoplasm with multiple phosphorylation sites. Combined with predictive analysis of conserved domains, this protein belongs to the HAD(haloacid dehalogenase)superfamily; prokaryotic expression studies show that the size of the CpPMM fusion protein is about 29 kDa, which is consistent with the relative molecular mass predicted. The target protein is an inclusion body and is partially soluble. The qRT-PCR results showed that the CpPMM gene exerted spatiotemporal expression patterns, and the expression level in fruiting period was significantly higher than that in the other three periods such as the flowering period. Along with the growth period of C. pilosula, the polysaccharide content of C. pilosula showed a gradual increase trend, reaching the highest during the harvest time. And there are significant differences in the polysaccharide content of C. pilosula in each period. In this study, the CpPMM gene was cloned from the root of C. pilosula, at the same time, the prokaryotic expression system was constructed. In addition, its gene expression level is highly correlated with the polysaccharide content of C. pilosula. It lays the foundation for further studying the function of CpPMM gene and the analysis of biosynthetic pathways of polysaccharides in medicinal plants.

Is repair of the protruded meninges sufficient for treatment of meningocele?

PURPOSE: The present study aimed to investigate the relationship between meningocele and tethered cord syndrome, diagnosis of meningocele associated with tethered cord syndrome, and when to perform surgery and the best surgical procedure. METHODS: Sixty-nine children with meningocele who were admitted to Shanghai Children's Medical Center were analyzed. The relationship between meningocele and other lesions causing tethered cord syndrome was studied by combining magnetic resonance imaging (MRI) and intraoperative findings. RESULTS: The MRI results and intraoperative findings showed that 67 children (97%) had associated lesions such as tight filum terminale, fibrous band tethering, spinal cord or cauda equina adhesion, diastematomyelia, arachnoid cyst, and epidermoid cyst. The protruded meninges were repaired, and the intraspinal lesions were treated at the same time. Also, the tethered spinal cord was released. No neurological injuries were observed after surgery. CONCLUSIONS: The rate of meningocele associated with tethered cord syndrome is very high. MRI is necessary for the diagnosis of meningocele. Active surgical treatment is recommended immediately after definite diagnosis. During surgery, the surgeon should not only repair the protruded meninges but also explore the spinal canal and release the tethered cord.

Atorvastatin prevents angiotensin II-induced high permeability of human arterial endothelial cell monolayers via ROCK signaling pathway.

Intracranial aneurysm, as a common cause of cerebral hemorrhage, is often discovered when the aneurysm ruptures, causing subarachnoid hemorrhage. Unfortunately, the formation of cerebral aneurysm, which is associated with endothelial damage and macrophage migration, still cannot be prevented now. Tight junctions (TJs) open due to the disappearance of TJ proteins occludin and zona occludens-1 (ZO-1) in damaged endothelia, thus allowing macrophage migration and forming cerebral aneurysm. Therefore, cerebral aneurysm formation can be prevented by increasing TJs of the artery endothelium. Interestingly, statin, which can reduce saccular aneurysm, may prevent aneurysm formation through acting on different steps, but the underlying mechanism remains unclear. In this study, angiotensin II (Ang II) significantly increased the permeability of human arterial endothelial cell (HAEC). Moreover, the distribution of ZO-1 in cell-cell junction area and the total expression in HAECs were significantly decreased by Ang II treatment. However, the abnormal distribution and decreased expression of ZO-1 and hyperpermeability of HAECs were significantly reversed by pretreatment with atorvastatin. Furthermore, Ang II-induced phosphorylations of MYPT1, LIMK and MLC2 were significantly inhibited with atorvastatin or Rho kinase (ROCK) inhibitor (H1152) pretreatment. Knockdown of ROCK-II probably abolished Ang II-induced abnormal ZO-1 distribution and expression deficiency and hyperpermeability of HAECs. In conclusion, atorvastatin prevented Ang II-induced rupture of HAEC monolayers by suppressing the ROCK signaling pathway. Our results may explain, at least in part, some beneficial effects of statins on cardiovascular diseases such as intracranial aneurysm.

Gene therapy with RNAi targeting UHRF1 driven by tumor-specific promoter inhibits tumor growth and enhances the sensitivity of chemotherapeutic drug in breast cancer in vitro and in vivo.

UHRF1, also known as ICBP90 (inverted CCAAT box binding protein 90) in human, is a nuclear protein that acts as a fundamental regulator in cell proliferation and maintains DNA methylation. It is reported that UHRF1 is obviously upregulated in various human malignancies, but unchanged in differentiated tissues, suggesting that UHRF1 plays a crucial role in carcinogenesis and can be a useful anticancer drug target. In this study, we explored whether UHRF1 can be a therapeutic target for human breast carcinoma. We successfully constructed the tumor-specific shRNA expression vector driven by survivin promoter targeting UHRF1 gene. The tumor-specific RNA interference system efficiently and specifically knocked down UHRF1 expression, induced the apoptosis of tumor cells, and enhanced chemosensitivity of tumor cells to cisplatinum, but not in normal cells in vitro and in vivo. Therefore, the survivin promoter-driving shRNA expression system targeting UHRF1 may play a vital and potential role for the treatment of specificity and high efficacy in human breast carcinomas.

Double strand RNA-guided endogeneous E-cadherin up-regulation induces the apoptosis and inhibits proliferation of breast carcinoma cells in vitro and in vivo.

E-cadherin plays a crucial role in epithelial cell-cell adhesion and in the maintenance of tissue architecture. Down-regulation of E-cadherin expression correlates with a strong invasive potential, resulting in poor prognosis in many human carcinomas, including breast cancer. Restoration of E-cadherin can inhibit cell invasion and metastasis in many types of tumors. It has been demonstrated that promoter hypermethylation causes transcriptional down-regulation of E-cadherin. Here, using an RNAa technique specifically activating the expression of E-cadherin through transcriptional regulation, we assessed the phenotype changes of a breast carcinoma cell line with transfection of small-activating RNAs (saRNAs). We observed cell apoptosis, proliferation inhibition and reduction in human breast cancer migration in vitro. Animal experiment results showed that saRNA could inhibit tumor growth in vivo compared with scramble double-small RNA (dsRNA).This study provides a new potential strategy for breast cancer therapy, and also demonstrates the potential for saRNA as a therapeutic option for enhancing tumor suppressor gene expression in breast cancer. (Cancer Sci 2010).

Downregulation of stathmin expression is mediated directly by Egr1 and associated with p53 activity in lung cancer cell line A549.

Stathmin is overexpressed in a variety of assessed human malignancies and is correlated with tumor progression and poor prognosis. Downregulation of its expression will contribute to optimize therapeutic outcomes in the treatment of various malignancies. However, the mechanisms of stathmin gene overexpression are not completely elucidated at present. Early growth response 1 (Egr1) is a transcription factor that triggers transcription of downstream genes mediating cell growth and angiogenesis upon various stimulations. Following the previous computational identification of a site that was thought to be an Egr1 consensus binding sequence at -85 to -94 region in stathmin gene promoter, we analyzed the role of Egr1 in the regulation of stathmin gene expression in lung cancer cell line A549. The results showed that Egr1 transcription factor bound to the sequence 5'-GCGGGGGCG-3' within human stathmin gene promoter; and in reporter gene assays and overexpression experiments, both stathmin gene promoter activity and stathmin gene expression level were downregulated following endogenous or exogenous expression of Egr1. Using wild type Egr1 and knockout Egr1 cell lines, we demonstrated that p53 negatively regulates stathmin expression through Egr1 pathway. In summary, Egr1 is a novel regulator of stathmin expression and p53 mediates the transcriptional repression of stathmin by Egr1 in human lung cancer cells.

Enhanced hippocampal neurogenesis in the absence of microglia T cell interaction and microglia activation in the murine running wheel model.

Recently, activated microglia have been shown to be involved in the regulation of several aspects of neurogenesis under certain experimental conditions both in vitro and in vivo. A neurogenesis supportive microglia phenotype has been suggested to arise from the interaction of microglia with homing encephalitogenic T cells. However, a unified hypothesis regarding the exact nature of microglia activity that is supportive of neurogenesis is yet missing from the field. Our aim was to investigate the connection between microglia activity and adult hippocampal neurogenesis under physiological conditions. To address this question we compared the level of microglia activation in the hippocampus of mice, which had access to a running wheel for 10 days and that of sedentary controls. Surprisingly, despite elevated levels of proliferation of neural precursors and survival of newborn neurons in the dentate gyrus microglia remained in a "resting" state morphologically, antigenically, and at the transcriptional level. Moreover, neither T cells nor MHCII expressing microglia were present in the hippocampal brain parenchyma. Though microglia in the dentate gyrus of the runners proliferated at a higher level than in the sedentary controls, this difference was also present in non-neurogenic sites. Therefore, our findings suggest that classical signs of microglia activation and microglia activation arising from interaction with T cells in particular are not a prerequisite for the activity-induced increase in adult hippocampal neurogenesis in C57Bl/6 mice. Thus, our results draw attention on the species and model differences that might exist regarding the regulation of adult hippocampal neurogenesis.

Expression of stathmin/op18 as a significant prognostic factor for cervical carcinoma patients.

PURPOSE: Stathmin (Oncoprotein18), a ubiquitous and highly conserved 19-kDa cytosolic phosphoprotein, has been reported to play a critical role in mitosis and possibly other cellular processes, which is associated with tumor carcinogenesis and development. The purpose of this study was to examine the involvement of stathmin in human cervical carcinogenesis and to evaluate its prognostic significance in human cervical carcinoma. METHODS: Using semiquantitative RT-PCR and Western blotting, we detected the expression of stathmin in human normal cervical epithelial cell line, immortalized cervical epithelial cell lines, and cervical carcinoma cell lines. Additionally, we also detected the expression of stathmin protein in 15 cases of cervical carcinoma tissues and adjacent non-carcinomous margin tissues. Furthermore, specimens from 148 patients with different grade and stage cervical carcinoma were investigated by immunohistochemistry for stathmin expression. Correlations between the expression of stathmin and various clinicopathological factors were studied, while statistical analyses were performed to evaluate prognostic and diagnostic associations. RESULTS: The levels of stathmin mRNA and protein expression were significantly higher in cervical carcinoma cells and immortalized cervical epithelial cells than in normal cervical epithelial cells (P < 0.05). Moreover, Western blotting revealed high stathmin protein expression in 73.3% (11/15) cervical carcinoma tissues, while stathmin were overexpressed in tumor tissues as compared with adjacent non-carcinomous margin samples (P = 0.017). In addition, immunohistochemical staining revealed stathmin immunoreactivity in 81.1% (120/148) of cervical carcinoma tissues and high stathmin expression was significantly correlated with clinical stage (P = 0.006), T classification (P = 0.012), regional lymph node metastasis (P = 0.005) and hematogenous metastasis (P = 0.021). Kaplan-Meier analysis showed that high stathmin positivity was significantly associated with a shorter survival time (P < 0.001). Clinical stage (P = 0.0022), T classification (P = 0.0035), regional lymph node (P = 0.0008) or hematogenous metastasis (P = 0.0015) were also associated with survival time. Furthermore, by Cox multivariate analysis, only lymph node (P = 0.0052) or hematogenous metastasis (P = 0.0046) maintained their significance as independent prognostic factors, although stathmin was not an independent prognostic factor (risk ratio: 1.45; P = 0.0624). CONCLUSIONS: Stathmin expression correlates with cervical carcinogenesis and tumor progression. This molecule is a valuable prognostic marker in patients with cervical carcinoma.

Simultaneous determination of baicalin, rhein and berberine in rat plasma by column-switching high-performance liquid chromatography.

A simple HPLC method using column-switching and ultraviolet detection was developed for the simultaneous determination of baicalin (BA), rhein (RH) and berberine (BE) in rat plasma. Plasma samples were injected directly onto a Capcell Pak MF C(8) column (150 mm x 4.6 mm i.d.) to remove protein and to be pre-separated by an isocratic elution using 50 mmol/L phosphate sodium (pH 6.85)-acetonitrile (10:1, v/v). After the drug-containing fractions were transferred to a Kromasil C(18) column (150 mm x 4.6 mm i.d.) by a valve switching step, the valve position was switched back and the main separation was performed by an isocratic elution using triethylamine adjusted 20 mmol/L phosphoric acid (pH 6.78)-acetonitrile (4:1, v/v). The flow rate was always 1.0 mL/min. The calibration curve showed excellent linear relationship (r>or=0.9997) over the concentration range of 0.4-7.9 microg/mL for baicalin, 0.2-7.8 microg/mL for rhein and 0.4-7.7 microg/mL for berberine in rat plasma. The intra- and inter-day assay precisions (R.S.D.) of three analytes were in the range of 0.34-4.3% and the accuracies were between 98.0% and 102.4%. Their recoveries were all greater than 95%. The method was successfully applied to the multi-constituents plasma concentration-time curve study after oral administration of a traditional Chinese medicine prescription Xiexin-Tang in rats.