Gamma-glutamyl transferase 5 overexpression in cerebrovascular endothelial cells improves brain pathology, cognition, and behavior in APP/PS1 mice.

JOURNAL/nrgr/04.03/01300535-202502000-00030/figure1/v/2024-05-28T214302Z/r/image-tiff In patients with Alzheimer's disease, gamma-glutamyl transferase 5 (GGT5) expression has been observed to be downregulated in cerebrovascular endothelial cells. However, the functional role of GGT5 in the development of Alzheimer's disease remains unclear. This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer's disease, as well as the underlying mechanism. We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer's disease (Aß1-42-treated hCMEC/D3 and bEnd.3 cells), as well as in the APP/PS1 mouse model. Additionally, injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits. Interestingly, increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-ß in the brains of APP/PS1 mice. This effect may be attributable to inhibition of the expression of ß-site APP cleaving enzyme 1, which is mediated by nuclear factor-kappa B. Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer's disease pathogenesis, and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice. These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer's disease.

Case report: A pregnant woman accidental treated with spironolactone in mid-gestation.

Spironolactone, a potassium-sparing diuretic, is used to treat hypertension, heart failure, and certain hyperandrogenic disorders. Its use during pregnancy is not recommended due to the risk of feminizing male fetuses, primarily because of its antiandrogenic activity. However, human data remain scarce and largely inconclusive. Here, we present the first case of a 25-year-old pregnant woman, at 16 weeks of gestation, who was inadvertently exposed to spironolactone (240 mg/day) for 1 week due to a pharmacy dispensing error. The patient subsequently delivered a healthy male infant with normal genitalia at 38 weeks of gestation following vaginal delivery. Current follow-up shows that the infant is healthy and developing normally. This article summarizes the potential causes of spironolactone-induced anomalous genital development and explores the safety of new-generation mineralocorticoid receptor antagonists (MRAs) during pregnancy. The mechanisms behind spironolactone-induced anomalous genital development in male fetuses have not been fully elucidated. Spironolactone competes with dihydrotestosterone for binding to androgen receptors and inhibits enzymes involved in androgen biosynthesis, which may partly explain its antiandrogenic effects. Recent advancements in MRAs have led to the development of compounds with higher selectivity for the mineralocorticoid receptor, thereby reducing the incidence of antiandrogen side effects. These new-generation MRAs may be effective alternatives during pregnancy, but more data are needed to establish their safety in pregnant women. This case contributes to the limited but growing body of literature on the safety profile of spironolactone in pregnancy, providing insights into its effects during a critical period of fetal development.

Case Report: Taking action or standing by: managing a preterm neonate at the risk of neonatal varicella by metagenomic next-generation sequencing.

Neonatal varicella is indeed a rare condition, and most infants born to mothers with varicella have a good prognosis. However, in exceptional cases, neonatal varicella can be life-threatening, particularly for preterm infants. Therefore, it is vital to make an early diagnosis or predict the risk of neonatal varicella to ensure prompt treatment and improve prognosis. This report made an effort to early predict neonatal vericalla by using metagenomic next-generation sequencing (mNGS) in a preterm infant who was at risk for vericalla infection. A preterm infant born from a mother with varicella with symptom onset at 8 days before delivery, putting the infant at risk for varicella infection. Importantly, the patient develop pneumonia and pneumothorax, and neonatal vericella was suspected. Fortunately, the use of mNGS for testing the varicella gene in the serum promptly ruled out varicella zoster virus (VZV) infection in the patient, as indicated by a negative mNGS result. Subsequent follow-up, which included a 14-day stay in the hospital followed by an additional 7 days at home, confirmed this finding. Throughout this period, the patient did not exhibit any rash or other symptoms associated with varicella. Therefore, the novel approach of using mNGS allows neonatologists to predict and promptly address potential neonatal infections. This early detection is crucial, as delayed diagnosis or treatment could pose life-threatening risks, as exemplified by the case of neonatal varicella. In such cases, neonatologists can take proactive measures instead of standing by for at-risk neonates. Furthermore, given the severity of neonatal varicella as a life-threatening condition, the early exclusion of subsequent varicella infection by mNGS can offer reassurance to both family members and healthcare professionals.

The potential role of heparin-binding protein in neonatal sepsis: research progress.

Neonatal sepsis is a major global health challenge, leading to significant morbidity and mortality in newborns. The search for precise biomarkers for its early prediction in clinical settings has been ongoing, with heparin-binding protein (HBP) emerging as a promising candidate. Originating from granules in neutrophils, HBP is released into the bloodstream in response to infection and plays a pivotal role in the body's inflammatory response. Its significance extends beyond its inflammatory origins; research indicates dynamic changes in HBP levels are strongly linked to reduce in-hospital mortality, offering a prognostic advantage over existing biomarkers. Furthermore, HBP has demonstrated considerable clinical utility in the early diagnosis and stratification of neonatal sepsis, suggesting its potential as a reliable blood marker for early prediction of the disease and its severity. Its application may extend to guiding the judicious use of antibiotics in treating newborns, addressing a critical aspect of neonatal care. Despite these encouraging results, the precise clinical utility of HBP for diagnosing and treating sepsis in neonates still demands further clarification through extensive research. This review delves into the current scientific understanding of HBP's contribution to diagnosing, prognosticating, and treating neonatal sepsis, while considering its future clinical applications.

Case report: Acute severe hyponatremia-induced seizures in a newborn: a community-acquired case and literature review.

Severe neonatal hyponatremia represents a critical electrolyte imbalance with potentially severe neurological outcomes, a condition rarely documented in community-acquired, full-term newborns. This report underscores a unique case of a 23-day-old, previously healthy, full-term male neonate experiencing severe hyponatremia that precipitated seizures, underscoring the urgency of prompt recognition and intervention. The neonate presented with symptoms including vomiting, groaning, chills, fixed staring, and limb tremors. Critical findings upon admission encompassed hypothermia, hypotension, tachycardia, and tachypnea accompanied by significant weight loss. The clinical presentation was marked by dehydration, lethargy, weak crying, a fixed gaze, irregular breathing, and coarse lung sounds, yet a distended abdomen, hypertonic limb movements, and recurrent seizures were observed. Immediate interventions included establishing IV access, rewarming, mechanical ventilation, seizure management, volume expansion, dopamine for circulatory support, and initiation of empirical antibiotics. Diagnostic evaluations revealed a sodium ion concentration of 105.9 mmol/L, while amplitude-integrated electroencephalography (aEEG) detected pronounced seizure activity characterized by a lack of sleep-wake rhythmicity, noticeable elevation in both the lower and upper amplitude margins, and a sustained decrease in the lower margin voltage dropping below 5 µV, presenting as sharp or serrated waveforms. The management strategy entailed rapid electrolyte normalization using hypertonic saline and sodium bicarbonate, anticonvulsant therapy, and comprehensive supportive care, with continuous aEEG monitoring until the cessation of seizures. Remarkably, by the third day, the neonate's condition had stabilized, allowing for discharge in good health 10 days post-admission. At a 16-month follow-up, the child exhibited no adverse neurological outcomes and demonstrated favorable growth and development. Our extensive review on the etiology, clinical manifestations, aEEG monitoring, characteristics of seizures induced by severe neonatal hyponatremia, treatment approaches, and the prognosis for seizures triggered by severe hyponatremia aims to deepen the understanding and enhance clinical management of this complex condition. It stresses the importance of early detection, accurate diagnosis, and customized treatment protocols to improve outcomes for affected neonates. Additionally, this review accentuates the indispensable role of aEEG monitoring in managing neonates at elevated risk for seizures. Yet, the safety and efficacy of swiftly administering hypertonic saline for correcting severe hyponatremia-induced seizures necessitate further investigation through medical research.

TAT-Modified Martentoxin Displays Intravenous Antiseizure Activities.

Epilepsy is a chronic disease of brain dysfunction, which arises from imbalance between excitatory and inhibitory activities in neural circuits. Previously, we reported that peptide Martentoxin (MarTX), from scorpion Buthus martensii Karsch, displayed antiseizure activities by specifically inhibiting BK(α + ß4) channel currents. Injection of MarTX into the hippocampal region of mice significantly alleviated convulsive seizures. However, intravenous injection of MarTX had no antiepileptic efficacy due to the blood-brain barrier (BBB). To address this, here, we designed cell-penetrating peptide TAT-modified MarTX, in which the linker containing three glycines was put between TAT and the N-terminus of MarTX (forming MTX-N-TAT) or between TAT and the C-terminus of MarTX (forming MTX-C-TAT), respectively. We prepared them in a large amount through Escherichia coli overexpression system and then probed their antiseizure activities. Our results indicated that intravenous injection of MTX-C-TAT showed significant therapeutic efficacy of antiseizure. It increased seizure latency, reduced the total seizure duration and the number of seizures at stages 3, 4, and 5, inhibited hippocampal neuronal hyperexcitability, and exhibited neuroprotective effects on hippocampal neurons. These studies implied that MTX-C-TAT displayed intravenous antiseizure activities properly through crossing BBB and would be a potential antiepileptic drug in the future.

Summary of the application value of ultrasound imaging features in the clinical differential diagnosis of intramuscular capillary-type hemangioma and fibro-adipose vascular anomaly.

Objective: To investigate the value of ultrasonography as a diagnostic aid in differentiating intramuscular capillary-type hemangioma (ICTH) from fibro-adipose vascular anomaly (FAVA). Methods: A retrospective analysis was conducted of the clinical and ultrasound imaging data of 20 patients with ICTH and 45 patients with FAVA who were admitted to and pathologically confirmed in hospital between January 2013 and April 2023. The clinical and ultrasonographic appearances of the lesions in the two groups were compared and analyzed. A stepwise regression analysis was performed, and a joint diagnostic equation was constructed using the final variables selected. The receiver operating characteristic (ROC) curve and indicators, including sensitivity and specificity, were used to evaluate the efficacy of the joint diagnostic model. Results: The two groups of patients suffering from ICTH and FAVA presented a statistically significant difference (P< 0.05) in terms of 'age', 'lesion size', 'fascial tail sign', 'presence of a fatty-tissue-like hyperecho around the lesion', 'blood flow' and 'presence of straight blood capillaries within the lesion'. Finally, the variables 'fascial tail sign' and 'presence of straight blood capillaries within the lesion' were selected to construct the model. The constructed joint diagnostic model had a sensitivity value of 70.0% (95% CI: 59.00-81.00), a specificity value of 98.0% (95% CI: 94.70-100.00) and a ROC curve value of 0.908, indicating the high efficacy of the combined diagnosis method. Conclusions: Ultrasonography can be utilized to differentiate ICTH from FAVA, and the combined diagnosis method can further improve the technique's diagnostic efficacy.

Case report: Catastrophic event: neonatal gastric perforation and complication of capillary leak syndrome.

Neonatal gastric perforation (NGP) is a rare, but life-threatening condition that can lead to serious conditions, such as capillary leak syndrome (CLS). Here, we present the case of a preterm male infant with NGP complicated by CLS after stomach repair. The patient was born at 33 2/7 weeks, weighed 1,770 g, and was diagnosed with respiratory distress syndrome. On the fourth day of life, the patient presented with distention and an unstable cardiovascular system. Routine blood tests revealed a white blood cell count of 2.4 × 109/L. Chest and abdominal radiography revealed a pneumoperitoneum, suggesting a gastrointestinal perforation. The patient was urgently transferred to a tertiary hospital for exploratory laparotomy, where a 2 cm diameter perforation was discovered in the stomach wall and subsequently repaired. Pathological findings indicated the absence of a muscular layer in the stomach wall. The patient unexpectedly developed CLS postoperatively, leading to multiorgan dysfunction and eventual death. The underlying pathological mechanism of NGP-induced CLS may be related to severe chemical peritonitis, sepsis, endothelial glycocalyx dysfunction, enhanced systemic inflammation, and translocation of the gut microbiota, causing endothelial hyperpermeability. Notablely, abdominal surgery itself can be a significant triggering factor for CLS occurrence. Complications of NGP and CLS are extremely dangerous. Investigating the mechanism by which NGP triggers CLS could potentially improve the prognosis. Conservative treatment for pneumoperitoneum secondary to gastric perforation may be a reasonable option, especially when the condition of the patient is unstable.

Puerarin Prevents Bisphenol S Induced Lipid Accumulation by Reducing Liver Lipid Synthesis and Promoting Lipid Metabolism in C57BL/6J Mice.

Bisphenol S (BPS) is an environmental pollutant that can accumulate in the human body and cause harm. Puerarin (PUE) is a flavonoid with anti-inflammatory and antioxidant effects. In this study, we used 50 mg/kg/d BPS as a poison and PUE as an intervention for model mice for 42 d. BPS exposure significantly increased the levels of the impairment of the mice's liver function, T-CHO, TG, LDL-C, ALT, and AST in the BPS group were significantly increased (p < 0.05). Additionally, BPS exposure caused inflammatory cell infiltration in the mice liver tissue and enhanced oxidative stress response, the level of MDA was significantly increased (p < 0.05). The expression of CD36 and pparγ was stimulated after BPS exposure. Moreover, the expression of cpt1a and cpt1b, which promote fatty acid oxidation, was downregulated. After PUE intervention, the levels of genes and proteins involved in lipid synthesis (PPARγ, SREBP1C, and FASN) and metabolism (Cpt1a, Cpt1b, and PPARα) in mice returned to those of the control group, or much higher than those in the BPS group. Therefore, we hypothesized that BPS causes lipid accumulation in the liver by promoting lipid synthesis and reducing lipid metabolism, whereas PUE reduces lipid synthesis and promotes lipid metabolism. Conclusively, our results imply that long-term exposure to BPS in mice affects liver lipid metabolism and that PUE intervention could maintain the liver function of mice at normal metabolic levels.

Self-interest or altruism: Entrepreneurs' military experience and the motivation of corporate philanthropic donations.

This study aims to explore the motivation of corporate philanthropic donations through investigating the impact of entrepreneurs' military experience. Based on the data from the 12th Chinese privately owned enterprises survey, this study finds that entrepreneurs' military experience has a positive impact on corporate philanthropic donations and the result keeps consistent after a series of robustness tests. Further, corporate financing constraints do not significantly influence the relationship between entrepreneurs' military experience and corporate philanthropic donations, while return on equity (ROE) strengthens the relationship. Therefore, entrepreneurs with military experience still donate even if their firms suffer from financial constraints. When firms achieve higher ROE, they will donate more. The findings suggest that the donations of firms with military entrepreneurs are more likely to be altruistic, enriching the understanding of the motivation of corporate philanthropic donations.

Evaluating a Panel of Autoantibodies Against Tumor-Associated Antigens in Human Osteosarcoma.

Background: The aim of this study was to identify a panel of candidate autoantibodies against tumor-associated antigens in the detection of osteosarcoma (OS) so as to provide a theoretical basis for constructing a non-invasive serological diagnosis method in early immunodiagnosis of OS. Methods: The serological proteome analysis (SERPA) approach was used to select candidate anti-TAA autoantibodies. Then, indirect enzyme-linked immunosorbent assay (ELISA) was used to verify the expression levels of eight candidate autoantibodies in the serum of 51 OS cases, 28 osteochondroma (OC), and 51 normal human sera (NHS). The rank-sum test was used to compare the content of eight autoantibodies in the sera of three groups. The diagnostic value of each indicator for OS was analyzed by an ROC curve. Differential autoantibodies between OS and NHS were screened. Then, a binary logistic regression model was used to establish a prediction logistical regression model. Results: Through ELISA, the expression levels of seven autoantibodies (ENO1, GAPDH, HSP27, HSP60, PDLIM1, STMN1, and TPI1) in OS patients were identified higher than those in healthy patients (p < 0.05). By establishing a binary logistic regression predictive model, the optimal panel including three anti-TAAs (ENO1, GAPDH, and TPI1) autoantibodies was screened out. The sensitivity, specificity, Youden index, accuracy, and AUC of diagnosis of OS were 70.59%, 86.27%, 0.5686, 78.43%, and 0.798, respectively. Conclusion: The results proved that through establishing a predictive model, an optimal panel of autoantibodies could help detect OS from OC or NHS at an early stage, which could be used as a promising and powerful tool in clinical practice.

Corporate social responsibility and cross-border M&A: The moderating effect of institutional distance.

Drawing upon a dataset of cross-border mergers and acquisitions (M&A) events of Chinese enterprises from 2010 to 2017, this study investigates the impact of corporate social responsibility (CSR) on the completion of cross-border M&A with a focus on the moderating role of institutional distance. The results highlight the significance of CSR on the completion of cross-border M&A. The robustness tests including changing estimation model, new measurements, propensity score matching, and instrumental variable tests show that the main results are consistent. Second, both formal and informal institutional distance have positive moderating effects of CSR on the completion of cross-border M&A.

MiR-485-3p serves as a biomarker and therapeutic target of Alzheimer's disease via regulating neuronal cell viability and neuroinflammation by targeting AKT3.

BACKGROUND: Numerous microRNAs (miRNAs) have been identified as functional molecules in Alzheimer's disease (AD) pathogenesis. This study aimed to investigate the diagnostic value of microRNA-485-3p (miR-485-3p) in AD patients, evaluate the effect of miR-485-3p on neuronal viability and neuroinflammation, as well as the underlying molecular mechanisms. METHODS: Quantitative Real-Time PCR was used to estimate expression of miR-485-3p and AKT3. A ROC analysis was used to evaluate the diagnostic value of miR-485-3p. The correlation of miR-485-3p with patients' MMSE score and inflammatory response was analyzed. Using Aß-treated SH-SY5Y and BV2 cells models, the effects of miR-485-3p on neuronal proliferation, apoptosis, and neuroinflammation were explored. A luciferase reporter assay was used to confirm the target gene of miR-485-3p in both SH-SY5Y and BV2 cells. RESULTS: Serum miR-485-3p expression was significantly upregulated in AD patients and cell models, which had a high diagnostic accuracy and correlated with MMSE score and inflammatory response in AD patients. The knockdown of miR-485-3p in SH-SY5Y and BV2 cells was found to significantly reverse the effect of Aß treatment on neuronal viability and neuroinflammation. AKT3 was determined as a target of miR-485-3p, which might mediate the biological function of miR-485-3p in AD pathogenesis. CONCLUSION: All the data indicated that increased serum miR-485-3p serves as a diagnostic biomarker in AD patients, and knockdown of miR-485-3p exerts a neuroprotective role by improving neuronal viability and weakening neuroinflammation, which may be mediated by AKT3. This study may provide a novel biomarker and therapeutic target for AD therapy.

MicroRNA-150 serves as a diagnostic biomarker and is involved in the inflammatory pathogenesis of Parkinson's disease.

BACKGROUND: Dysregulation of microRNAs (miRNAs) has been reported to be involved in the neuroinflammatory pathogenesis of PD. This study aimed to investigate the serum expression of microRNA-150 (miR-150) in Parkinson's disease (PD) patients and further uncover the regulatory effect of miR-150 on neuroinflammation. METHODS: Quantitative Real-Time PCR was used to measure the expression of miR-150. A receiver operating characteristic curve was applied to evaluate the diagnostic value of miR-150. The effect of miR-150 on neuroinflammation was analyzed by examining its correlation with proinflammatory cytokines and gain-of-function experiments in microglia treated with LPS. RESULTS: Serum miR-150 expression was downregulated in PD patients compared with the healthy controls, and served as a candidate diagnostic biomarker for the screening of PD cases. Negative correlation was found between miR-150 levels and the levels of procytokines in PD patients. By the treatment of LPS, microglia BV2 cells had a reduced expression of miR-150, and the enhanced neuroinflammatory responses were inhibited by the overexpression of miR-150. AKT3 was verified as a target of miR-150 in BV2 cells. CONCLUSION: All the data of this study revealed that the decreased serum miR-150 serves as a potential diagnostic biomarker. The methods to increase miR-150 expression may have a beneficial effect in PD via suppressing the neuroinflammation by targeting AKT3.

Mesoporous silicas templated by heterocyclic amino acid derivatives: Biomimetic synthesis and drug release application.

The present paper reported a biomimetic synthesis of mesoporous silicas (BMSs) at room temperature by using synthesized polymers (C16-l-His, C16-l-Pro and C16-l-Trp) which derived from amino acid with ring structures as template under basic condition via co-structural-directing-agent method. The formation mechanism of BMSs and effect of initial synthesis conditions (such as surfactant structure, pH and co-solvents) on morphology and structure of BMSs were systematically studied. Synthesized BMSs were characterized by transmission electron microscope (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and nitrogen adsorption/desorption isotherms. The results showed that the surfactant structure was the dominant factor to direct the final mesostructure of BMSs, since the structure of surfactant affected the structure and size of clusters. Meanwhile the generation of BMSs required very rigorous alkaline condition which controlled the ionization degree of the surfactant and thus contributing to adequate stacking energy. Higher pH resulted in construction of channels with higher curvature. The presence of ethanol was found to facilitate the formation of BMSs with larger particle size. In application, aspirin can be loaded into BMSs with high efficiency, and the drug crystalline state of aspirin transformed from crystalline state to amorphous state during this process, which undoubtedly lead to the improvement of drug dissolution from 72.8% to 100% within 90 min. It is convincible that the biomimetic method presented here provided novel insight on precisely control of mesoporous silica and undoubtedly promoted the application of mesoporous silica materials.

Systematic modifications of amino acid-based organogelators for the investigation of structure-property correlations in drug delivery system.

Thermogels, used as multi-functional drug-loading materials, have properties that mainly rely on their gelator structure. Although a large variety of organogel systems are used as drug delivery carriers, relatively few have been investigated in terms of their structure-property correlations based on amino acid derivative gelators. Here, a series of amino acid based gelators were synthesized to explore the role of the gelator structure on functional properties, with the aim of establishing a connection between the molecular parameters and gel properties. By varying the three substitutions of the gelator backbone, it was found that a comprehensive interaction, consisting of hydrophobic forces, H-bonding interactions, conformational flexibility and steric repulsion, play a crucial role in determining the gelation properties. Hansen solubility parameters were employed to explore the solvent effect on the network forming and gel properties. From an analysis of the morphologies obtained from polarized optical microscope (POM), atomic force microscopic images (AFM) and scanning electron microscopy (SEM), the gelator structure was found to have an impact on the self-assembly. According to the X-ray diffraction (XRD), the possible conformations adopted by the gelators were revealed through molecular modelling. The ability to form intermolecular H-bonding is vital in molecular packing and, thus, gelation. A structure-property relationship was developed and proposed to provide a theoretical basis for controllable drug delivery implants.

Biomimetic synthesis and evaluation of histidine-derivative templated chiral mesoporous silica for improved oral delivery of the poorly water-soluble drug, nimodipine.

In this study, spherical shaped chiral mesoporous silica nanoparticles (CMS) was biomimetic synthesized using histidine derivatives (C16-L-histidine) as template via the sol-gel reaction and employed as poorly water-soluble drug nimodipine (NMP) carrier. Characteristics of CMS and its application as drug carrier were intensively investigated and compared with MCM41. Then NMP was respectively loaded into CMS and MCM41 with the drug: carrier weight ratio of 2:1. Structural features of NMP before and after drug loading were systemically characterized. The results demonstrated that hydrogen bonds were formed between NMP and carriers during the drug loading process. After drug loading, crystalline state of NMP effectively converted into modification L and amorphous state, and the first form turned out to be easily removed by washing. On the other hand, drug dissolution rate was significantly improved after drug loading, and the best result came from NMP-C3 sample. It was able to release 17.83% of drug within 60 min, which was 6.8-fold higher than the release amount of pure NMP. Undoubtedly, NMP-C3 presented the highest relative bioavailability (386.22%), and the best therapeutic effect. Meanwhile, CMS improved the brain distribution of NMP in vivo.

Design of an Intelligent Nursing Clinical Pathway and Nursing Order Support System for Traditional Chinese Medicine.

With an in-depth analysis of nursing work in 14 hospitals over a period of two years, one unique total nursing information system framework was established where the nursing clinical pathways are used as the main frame and the nursing orders as the nodes on the frame. We used the nursing order concept with the principles of nursing process. A closed-loop management model composed of the nursing orders was set up to solve nursing problems. Based on the principles of traditional Chinese medicine, we further designed an intelligent support module to automatically deduct clinical nursing pathways to promote standardized management and improve the quality of nursing care. The system has successfully been implemented in some facilities since 2015.

Particle formation by supercritical fluid extraction and expansion process.

Supercritical fluid extraction and expansion (SFEE) patented technology combines the advantages of both supercritical fluid extraction (SFE) and rapid expansion of supercritical solution (RESS) with on-line coupling, which makes the nanoparticle formation feasible directly from matrix such as Chinese herbal medicine. Supercritical fluid extraction is a green separation technology, which has been developed for decades and widely applied in traditional Chinese medicines or natural active components. In this paper, a SFEE patented instrument was firstly built up and controlled by LABVIEW work stations. Stearic acid was used to verify the SFEE process at optimized condition; via adjusting the preexpansion pressure and temperature one can get different sizes of particles. Furthermore, stearic acid was purified during the SFEE process with HPLC-ELSD detecting device; purity of stearic acid increased by 19%, and the device can purify stearic acid.

Durability of transgene expression and vector integration: recombinant SV40-derived gene therapy vectors.

Many applications of gene delivery require long-term transgene expression. In dividing cells, this result necessitates vector genome persistence, usually by integrating into cellular DNA. Since recombinant gene delivery vectors derived from tag-deleted, replication-incompetent simian virus-40 (SV40) provide for long-term transgene expression in resting and dividing cells, we tested whether such enduring transgene expression reflected integration into cellular genomes. Several lines of evidence suggested this likelihood. After transduction in vitro, continuously dividing cell lines and continuously stimulated primary cells uniformly showed transgene expression for many months. Mice whose livers were transduced in vivo, partially resected, and allowed to regenerate showed comparable levels of transgene expression in regenerated and preoperative livers. Thus, replicationincompetent SV40 vectors (rSV40) persist in vitro and in vivo despite extensive cell division. We tested the possibility that this persistence reflected integration directly. Southern blot analyses of genomic DNA from transduced 293 cells showed that vector genome incorporation into cell DNA happened within days of transduction. Episomal vector DNA was barely detectable 96 hours post-transduction. Inverted PCR, used to characterize vector integration points, showed vector DNA integrated randomly into the cell genome. The circular rSV40 genome opened at different points in each integrand. A significant proportion of the integrands did not contain the entire vector sequence, but rather only portions thereof. Quantitative Southern blot analysis showed approximately 3.05 transgene copies per cell. Therefore, recombinant SV40 gene delivery vectors integrate into the cellular DNA of both resting and dividing cells, and do so randomly and within days of transduction. This integration may explain long-term transgene expression.