Research progress of propofol in alleviating cerebral ischemia/reperfusion injury.

Ischemic stroke is a leading cause of adult disability and death worldwide. The primary treatment for cerebral ischemia patients is to restore blood supply to the ischemic region as quickly as possible. However, in most cases, more severe tissue damage occurs, which is known as cerebral ischemia/reperfusion (I/R) injury. The pathological mechanisms of brain I/R injury include mitochondrial dysfunction, oxidative stress, excitotoxicity, calcium overload, neuroinflammation, programmed cell death and others. Propofol (2,6-diisopropylphenol), a short-acting intravenous anesthetic, possesses not only sedative and hypnotic effects but also immunomodulatory and neuroprotective effects. Numerous studies have reported the protective properties of propofol during brain I/R injury. In this review, we summarize the potential protective mechanisms of propofol to provide insights for its better clinical application in alleviating cerebral I/R injury.

Quantitative radiomics analysis of imaging features in adults and children Mycoplasma pneumonia.

Purpose: This study aims to explore the value of clinical features, CT imaging signs, and radiomics features in differentiating between adults and children with Mycoplasma pneumonia and seeking quantitative radiomic representations of CT imaging signs. Materials and methods: In a retrospective analysis of 981 cases of mycoplasmal pneumonia patients from November 2021 to December 2023, 590 internal data (adults:450, children: 140) randomly divided into a training set and a validation set with an 8:2 ratio and 391 external test data (adults:121; children:270) were included. Using univariate analysis, CT imaging signs and clinical features with significant differences (p < 0.05) were selected. After segmenting the lesion area on the CT image as the region of interest, 1,904 radiomic features were extracted. Then, Pearson correlation analysis (PCC) and the least absolute shrinkage and selection operator (LASSO) were used to select the radiomic features. Based on the selected features, multivariable logistic regression analysis was used to establish the clinical model, CT image model, radiomic model, and combined model. The predictive performance of each model was evaluated using ROC curves, AUC, sensitivity, specificity, accuracy, and precision. The AUC between each model was compared using the Delong test. Importantly, the radiomics features and quantitative and qualitative CT image features were analyzed using Pearson correlation analysis and analysis of variance, respectively. Results: For the individual model, the radiomics model, which was built using 45 selected features, achieved the highest AUCs in the training set, validation set, and external test set, which were 0.995 (0.992, 0.998), 0.952 (0.921, 0.978), and 0.969 (0.953, 0.982), respectively. In all models, the combined model achieved the highest AUCs, which were 0.996 (0.993, 0.998), 0.972 (0.942, 0.995), and 0.986 (0.976, 0.993) in the training set, validation set, and test set, respectively. In addition, we selected 11 radiomics features and CT image features with a correlation coefficient r greater than 0.35. Conclusion: The combined model has good diagnostic performance for differentiating between adults and children with mycoplasmal pneumonia, and different CT imaging signs are quantitatively represented by radiomics.

Lithium Therapy's Potential to Lower Dementia Risk and the Prevalence of Alzheimer's Disease: A Meta-Analysis.

INTRODUCTION: Dementia is a neurodegenerative disease with insidious onset and progressive progression, of which the most common type is Alzheimer's disease (AD). Lithium, a trace element in the body, has neuroprotective properties. However, whether lithium can treat dementia or AD remains a highly controversial topic. Therefore, we conducted a meta-analysis. METHODS: A systematic literature review was conducted on PubMed, Embase, and Web of Science. Comparison of the effects of lithium on AD or dementia in terms of use, duration, and dosage, and meta-analysis to test whether lithium therapy is beneficial in ameliorating the onset of dementia or AD. Sensitivity analyses were performed using a stepwise exclusion method. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of included studies. We determined the relative risk (RR) between patient groups using a random-effects model. RESULTS: A total of seven studies were included. The forest plot results showed that taking lithium therapy reduced the risk of AD (RR 0.59, 95% confidence interval [CI]: 0.44-0.78) and is also protective in reducing the risk of dementia (RR 0.66, 95% CI: 0.56-0.77). The duration of lithium therapy was able to affect dementia incidence (RR 0.70, 95% CI: 0.55-0.88); however, it is unclear how this effect might manifest in AD. It is also uncertain how many prescriptions for lithium treatment lower the chance of dementia development. CONCLUSION: The duration of treatment and the usage of lithium therapy seem to lower the risk of AD and postpone the onset of dementia.

Effect of neutrophil to lymphocyte ratio on prognosis of elderly patients with severe sepsis combined with diabetes mellitus.

BACKGROUND: To investigate the predictive value of neutrophil-to-lymphocyte ratio (NLR) in the short-term prognosis of elderly patients with severe sepsis combined with diabetes mellitus (DM). METHODS: The clinical data of 162 elderly patients with severe sepsis combined with DM from January 2018 to December 2022 were retrospectively collected. These patients were divided into a survival group (n = 104) and a death group (n = 58) according to 90-day prognosis. The number of neutrophils, lymphocytes, and NLR were compared. The optimal cut-off value for NLR to predict 90-day prognosis in elderly patients with severe sepsis combined with DM was determined using Receiver Operator Characteristic (ROC) curves, and the patients were divided into high and low NLR groups depending on the optimal cut-off value. The Kaplan-Meier method was used to plot the survival curves of the high and low NLR groups. Risk factors for the 90-day death in elderly patients with severe sepsis combined with DM were analyzed by a multivariate cox regression model. RESULTS: There were no significant differences in gender, age, history of hypertension and hyperlipidemia, intensive care unit (ICU) stay, duration of mechanical ventilation, and oxygenation index between the survival group and death group (p > 0.05). However, acute physiological and chronic health evaluation II (APACHE II) scores, and sepsis-related organ failure assessment (SOFA) scores were significantly lower in the survival group compared with the death group (p < 0.05). In the survival group, neutrophils counts and NLR were much lower than those in the death group, while lymphocytes counts were much higher (p < 0.05). ROC curves showed that the optimal cut-off value for NLR to predict 90-day mortality in elderly patients with severe sepsis combined with DM was 3.482. Patients were divided into high NLR and low NLR groups based on whether NLR was ≥ 3.482. In terms of the log-rank test results, patients in the low NLR group had a significantly higher 90-day survival rate than those in the high NLR group (Logrank χ2 = 8.635, p = 0.003). The multivariate cox regression model showed that the length of ICU stay longer than 15 days and NLR ≥ 3.482 were independent risk factors for 90-day prognosis in elderly patients with severe sepsis combined with DM. CONCLUSION: NLR ≥ 3.482 can be used to predict whether poor prognosis occurs in the short term after illness in elderly patients with severe sepsis combined with DM, and has good assessment value.

The effect of light therapy on sleep disorders and psychobehavioral symptoms in patients with Alzheimer's disease: A meta-analysis.

BACKGROUND: Although Alzheimer's disease (AD) mainly affects cognitive function, it is often accompanied by sleep disorders and psychobehavioral symptoms. These symptoms, including depression, agitation, and psychotic symptoms, are prominent hospitalization causes among patients with AD. Currently, relatively more research exists on light therapy for sleep disorders, while those on psychobehavioral symptoms are gradually increasing. However, no consensus exists on these results because of the vulnerability of light therapy to multiple factors, including light intensity and duration. Thus, further research investigating this aspect is warranted. OBJECTIVE: To evaluate the efficacy of light therapy in improving sleep disorders and psychobehavioural symptoms in patients with AD. METHODS: In this meta-analysis, relevant literature was searched in Embase, the Clinical Trials Registry, Web of Science, PubMed, and the Cochrane Library up to December 2022. Furthermore, a fixed-effects model was used for data analysis. RESULTS: Fifteen randomized controlled trials involving 598 patients with AD were included. In the case of sleep disorders, our meta-analysis revealed that light therapy significantly improved sleep efficiency (MD = -2.42, 95% CI = -3.37 to -1.48, p < 0.00001), increased interdaily stability (MD = -0.04, 95% CI = -0.05 to -0.03, p < 0.00001), and reduced intradaily variability (MD = -0.07, 95% CI = -0.10 to -0.05, p < 0.00001). With respect to psychotic behavior, light therapy was found to alleviate depression (MD = -2.55, 95% CI = -2.98 to -2.12, p < 0.00001) as well as reduce agitation (MD = -3.97, 95% CI = -5.09 to -2.84, p < 0.00001) and caregiver burden (MD = -3.57, 95% CI = -5.28 to -1.87, p < 0.00001). CONCLUSION: Light therapy leads to significant improvement in sleep and psychobehavioral symptoms and is associated with relatively fewer side effects in patients with AD, indicating its potential as a promising treatment option for AD.

SIRT3 improves alveolar epithelial cell damage caused by bronchopulmonary dysplasia through deacetylation of FOXO1.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a serious and long-term lung condition commonly observed in premature babies. Sirtuin 3 (SIRT3) has been reported to reduce pulmonary injury and pulmonary fibrosis. OBJECTIVE: The present study investigated the specific role of SIRT3 in BPD by establishing hyperoxia-induced BPD rat and cell models. Hematoxylin and eosin staining was used to observe pathological changes in lung tissues. MATERIALS AND METHODS: The expression levels of SIRT3 and forkhead box protein O1 (FOXO1), as well as its acetylation levels, were detected in hyperoxia-induced lung tissues and cells by Western blot analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Levels of reactive oxygen species, superoxide dismutase, and malondialdehyde were assessed by using biochemical kits. Following SIRT3 overexpression, the levels of inflammatory cytokines were assessed by RT-qPCR. Apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nickend labeling (TUNEL) and Western blot analysis. Upon FOXO1 knockout, cell inflammation, oxidative stress and apoptosis were evaluated again. RESULTS: Compared to the control group, the SIRT3 and FOXO1 expression levels were decreased and the FOXO1 acetylation levels were increased in hyperoxia-induced lung tissues and cells. In addition, SIRT3 reduced hyperoxia-induced inflammation, oxidative stress, and apoptosis in A549 cells, and inhibited FOXO1 acetylation to activate FOXO1. However, FOXO1 knockdown reversed the effects of SIRT3 overexpression in hyperoxia-induced A549 cells. CONCLUSION: SIRT3 relieved alveolar epithelial cell damage caused by BPD via deacetylation of FOXO1, suggesting that SIRT3 could be a therapeutic target in BPD.

Mechanism of Progesterone in Treatment of Traumatic Brain Injury Based on Network Pharmacology and Molecular Docking Technology.

BACKGROUND Previous studies have confirmed that progesterone has a protective effect on traumatic brain injury (TBI). In this paper, network pharmacology and molecular docking technology were used to further explore the potential mechanism of progesterone in the treatment of TBI. MATERIAL AND METHODS Based on network pharmacology, potential targets of progesterone for TBI were obtained. The network diagram of interactions between target proteins was established to screen the key targets of progesterone for TBI. The DAVID database was used to analyze its biological function and enrichment pathway, and to explore and determine the biological pathway of progesterone in treating TBI. Molecular docking technology was used to simulate the interaction between progesterone and key target proteins. RESULTS Progesterone can treat TBI by anti-inflammatory action, repairing damaged cell membranes, stabilizing the structure of the blood-brain barrier, alleviating brain edema, reducing neuronal apoptosis, and improving neurological function. The molecular mechanism involves the PI3K/Akt signaling pathway, MAPK signaling pathway, and Ras signaling pathway. CONCLUSIONS Progesterone is a potential clinical treatment for TBI. Exploring the potential targets and pathways of TBI therapy through network pharmacology can provide a direction for subsequent research.

Erratum to Application of magnetic resonance neurography in neonatal brachial plexus injury: A case report and literature review [Radiology Case Reports 17 (2022) 2859-2862].

[This corrects the article DOI: 10.1016/j.radcr.2022.04.017.].

Application of magnetic resonance neurography in neonatal brachial plexus injury: A case report and literature review.

Neonatal obstetric brachial plexus palsy is common in newborns with fetal macrosomia, especially those who are delivered vaginally with shoulder dystocia or breech delivery. The anatomical structure of brachial plexus in newborns is thin, and it is neither collinear nor coplanar in space; The location, the type and degree of neonatal brachial plexus injury need to be comprehensively judged by clinical history, neurological and imaging examination. Conventional MR imaging is not sufficient to diagnose brachial plexus injury. In this case report, we describe the clinical and imaging data of a newborn with brachial plexus injury diagnosed by the fat-suppressed T2-weighted sequence and MR myelography and confirmed by surgery. In addition, we review the related literature in an attempt to provide a better understanding of the principles and characteristics of neonatal brachial plexus injury diagnosed by magnetic resonance neurography.

The Nitrate Transporter MtNPF6.8 Is a Master Sensor of Nitrate Signal in the Primary Root Tip of Medicago truncatula.

Nitrate is not only an essential nutrient for plants, but also a signal involved in plant development. We have previously shown in the model legume Medicago truncatula, that the nitrate signal, which restricts primary root growth, is mediated by MtNPF6.8, a nitrate transporter. Nitrate signal also induces changes in reactive oxygen species accumulation in the root tip due to changes in cell wall peroxidase (PODs) activity. Thus, it was interesting to determine the importance of the role of MtNPF6.8 in the regulation of the root growth by nitrate and identify the POD isoforms responsible for the changes in POD activity. For this purpose, we compared in M. truncatula a npf6.8 mutant and nitrate insensitive line deficient in MtNPF6.8 and the corresponding wild and sensitive genotype for their transcriptomic and proteomic responses to nitrate. Interestingly, only 13 transcripts and no protein were differently accumulated in the primary root tip of the npf6.8-3 mutant line in response to nitrate. The sensitivity of the primary root tip to nitrate appeared therefore to be strongly linked to the integrity of MtNPF6.8 which acts as a master mediator of the nitrate signal involved in the control of the root system architecture. In parallel, 7,259 and 493 genes responded, respectively, at the level of transcripts or proteins in the wild type, 196 genes being identified by both their transcript and protein. By focusing on these 196 genes, a concordance of expression was observed for most of them with 143 genes being up-regulated and 51 being down-regulated at the two gene expression levels. Their ontology analysis uncovered a high enrichment in POD genes, allowing the identification of POD candidates involved in the changes in POD activity previously observed in response to nitrate.

[Ruifuping pectin protects against intestinal mucosal injury in the rat exertional heat stroke model].

OBJECTIVE: To evaluate the intestinal function in rats with exertional heat stroke (EHS) and explore the protective role of Ruifuping pectin (RFP) against heat related intestinal mucosal injury. METHODS: One hundred and twenty healthy special pathogen free (SPF) male Sprague-Dawley (SD) rats were randomly divided into normothermic control group, EHS model group, hyperthermic plus drinking water group (H2O+EHS group) and hyperthermic plus pectin group (RFP+EHS group) with 30 rats in each group. The rats in the H2O+EHS group and RFP+EHS group were given water 20 mL/kg or RFP 20 mL/kg orally for 5 days during adaptive training period. After 1 week, the temperature control range was adjusted to (37±1) centigrade using the temperature control treadmill, and the rat model of EHS was reproduced by one-time high temperature exhaustive exercise. No rehydration intervention was given during the training adaptation period in the EHS model group. The rats in the normothermic control group were maintained to room temperature (25±2) centigrade and humidity (55±5)% without other treatment. Behavior tests including withdraw response, righting, and muscle strength were performed immediately after onset of EHS. Blood of inferior vena cava was collected, and the serum inflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukins (IL-6, IL-1ß, IL-10)] and activity of diamine oxidase (DAO) were detected by enzyme linked immunosorbent assay (ELISA). The intestinal mucosa was collected, after hematoxylin-eosin (HE) staining, and Chiu score was performed to assess EHS induced pathological changes under light microscope. RESULTS: The rats in the EHS model group had behavioral, inflammatory and pathological changes, such as delayed withdraw response and righting, decreased forelimb pulling, increased inflammatory index, and obvious intestinal mucosal injury, which indicated that the reproduction of the EHS model was successful. There was no significant difference in above parameters between the H2O+EHS group and the EHS model group except that the inflammatory index in the RFP+EHS group was improved. Compared with the EHS model group, the withdraw reflex to pain and righting after RFP pretreatment in the RFP+EHS group were significantly improved (righting score: 1.4±0.2 vs. 0.3±0.2, withdraw reflex to pain score: 1.0±0.1 vs. 0.2±0.1, both P < 0.05), the muscle strength was significantly increased (N: 13.0±0.5 vs. 8.2±0.6, P < 0.01). The levels of pro-inflammatory factors in the RFP+EHS group were significantly lower than those in the EHS model group [TNF-α (ng/L): 67.5±9.2 vs. 194.3±13.7, IL-6 (ng/L): 360.0±54.1 vs. 981.2±84.4, IL-1ß (ng/L): 33.7±9.0 vs. 88.7±6.1, all P < 0.01], while the level of anti-inflammatory factor IL-10 was higher than that in the EHS model group (ng/L: 208.7±10.5 vs. 103.7±7.0, P < 0.01). The degree of intestinal mucosal injury in the RFP+EHS group was less severe than that in the EHS model group, and the Chiu score and DAO were significantly lower than those in the EHS model group [Chiu score: 1.5±0.2 vs. 3.8±0.0, DAO (U/L): 83.7±6.7 vs. 128.7±10.5, both P < 0.05]. CONCLUSIONS: High temperature training can damage the intestinal barrier function, and induce endotoxemia and systemic inflammatory response syndrome (SIRS) in rats. Oral prophylactic RFP can protect the intestinal barrier function, alleviate SIRS, and promote the recovery of basic nerve reflex and muscle strength after the occurrence of EHS in rats.

Sugar Signaling and Post-transcriptional Regulation in Plants: An Overlooked or an Emerging Topic?

Plants are autotrophic organisms that self-produce sugars through photosynthesis. These sugars serve as an energy source, carbon skeletons, and signaling entities throughout plants' life. Post-transcriptional regulation of gene expression plays an important role in various sugar-related processes. In cells, it is regulated by many factors, such as RNA-binding proteins (RBPs), microRNAs, the spliceosome, etc. To date, most of the investigations into sugar-related gene expression have been focused on the transcriptional level in plants, while only a few studies have been conducted on post-transcriptional mechanisms. The present review provides an overview of the relationships between sugar and post-transcriptional regulation in plants. It addresses the relationships between sugar signaling and RBPs, microRNAs, and mRNA stability. These new items insights will help to reach a comprehensive understanding of the diversity of sugar signaling regulatory networks, and open onto new investigations into the relevance of these regulations for plant growth and development.

Paeoniflorin inhibits cell viability and invasion of liver cancer cells via inhibition of Skp2.

Paeoniflorin (PF) has been demonstrated to exert tumor suppressive functions in various types of human cancer. However, the mechanisms of PF-mediated anti-tumor activity have not been fully elucidated. S-phase kinase associated protein 2 (Skp2) has been characterized as an oncoprotein that contributes to carcinogenesis. Therefore, the inhibition of Skp2 may be a useful approach for the treatment of various types of human cancer. The present study explored whether PF inhibited the expression of Skp2 in liver cancer cells, leading to cell viability inhibition, induction of apoptosis, and suppression of migration and invasion. PF treatment led to inhibition of Skp2 expression in liver cancer cells. The overexpression of Skp2 abolished PF-mediated anti-cancer activity, whereas the downregulation of Skp2 enhanced this type of activity. The data indicated that PF may be considered as a novel inhibitor of Skp2 in liver cancer cells.

Nitrate inhibits primary root growth by reducing accumulation of reactive oxygen species in the root tip in Medicago truncatula.

In Medicago truncatula, nitrate, acting as a signal perceived by NITRATE TRANSPORTER1/PEPTIDE TRANSPORTER FAMILY 6.8 (MtNPF6.8), inhibits primary root growth through a reduction of root cell elongation. Since reactive oxygen species (ROS) produced and converted in root tip (O2•- → H2O2 → •OH) have been reported to control cell elongation, the impact of nitrate on the distribution of these ROS in the primary root of M. truncatula was analyzed. We found that nitrate reduced the content of O2•-, H2O2 and •OH in the root tip of three wild type genotypes sensitive to nitrate (R108, DZA, A17), inhibition of root growth and O2•- accumulation being highly correlated. Nitrate also modified the capacity of R108 root tip to produce or remove ROS. The ROS content decrease observed in R108 in response to nitrate is linked to changes in peroxidase activity (EC1.11.1.7) with an increase in peroxidative activity that scavenge H2O2 and a decrease in hydroxylic activity that converts H2O2 into •OH. These changes impair the accumulation of H2O2 and then the accumulation of •OH, the species responsible for cell wall loosening and cell elongation. Accordingly, nitrate inhibitory effect was abolished by externally added H2O2 or mimicked by KI, an H2O2 scavenger. In contrast, nitrate has no effect on ROS production or removal capacities in npf6.8-2, a knockdown line insensitive to nitrate, affected in the nitrate transporter MtNPF6.8 (in R108 background) by RNAi. Altogether, our data show that ROS are mediators acting downstream of MtNPF6.8 in the nitrate signaling pathway.

The in vitro effects of gibberellin on human sperm motility.

Gibberellin, a plant growth regulator, is widely used to increase the shelf life and quality of fruits and vegetables. In this study, human semen samples were exposed to different concentrations of gibberellin, which reduced spermatozoa motility in vitro. Gibberellin exposure also increased levels of reactive oxygen species and the protein levels of apoptosis markers in human sperm. Gibberellin inhibited the activity of Na+/K+-adenosine triphosphatase (ATPase) and Ca2+-ATPase, which maintain the stability of ions inside and outside the membranes of spermatozoa. Moreover, gibberellin exposure suppressed adenosine triphosphate production and reduced the protein levels of adenosine triphosphate synthases, which may have induced the protein expression of adenosine 5'-monophosphate-activated protein kinase (AMPK) and its phosphorylated form. These results suggest that gibberellin reduces human sperm motility in vitro by increasing reactive oxygen species levels and reducing ATPase activity, which may upregulate AMPK and consequently reduce the fertilization potential of spermatozoa.

Innovative sludge pretreatment technology for impurity separation using micromesh.

In order to reduce the impacts on sludge treatment facilities caused by impurities such as fibers, hairs, plastic debris, and coarse sand, an innovative primary sludge pretreatment technology, sludge impurity separator (SIS), was proposed in this study. Non-woven micromesh with pore size of 0.40 mm was used to remove the impurities from primary sludge. Results of lab-scale tests showed that impurity concentration, aeration intensity, and channel gap were the key operation parameters, of which the optimized values were below 25 g/L, 0.8 m3/(m2 min), and 2.5 cm, respectively. In the full-scale SIS with treatment capacity of 300 m3/day, over 88% of impurities could be removed from influent and the cleaning cycle of micromesh was more than 16 days. Economic analysis revealed that the average energy consumption was 1.06 kWh/m3 treated sludge and operation cost was 0.6 yuan/m3 treated sludge.

MIGS as a Simple and Efficient Method for Gene Silencing in Rice.

MiRNA-induced gene silencing (MIGS) technology is a special kind of RNA interference technology that uses miR173 to mediate the production of trans-acting siRNA (ta-siRNA) to achieve target gene silencing. This technique has successfully mediated the silencing of interested genes in plants such as Arabidopsis, tobacco, petunia, etc. In order to establish the MIGS technology system in monocots such as rice, we constructed the MIGS backbone vectors pZHY930, pZHY931, pZHY932, and pZHY933 with different with promoters to regulate the expression of miR173 and miR173_ts. The rice OsPDS reporter gene was selected to compare the efficiency of four MIGS backbone vectors by the ratio of albino plants. The results showed that all the four backbone vectors could effectively mediate the target gene silencing, and pZHY932 showed highest efficiency up to 90%. Through MIGS silencing of endogenous OsROC5 and OsLZAY1 in rice, we successfully obtained rice mutant plants with rice leaf roll and tillering angles increasing, and further confirmed that MIGS backbone vector can efficiently mediate target gene silencing in rice. On the other hand, in order to verify the efficiency of MIGS-mediated multi-gene silencing in rice, we constructed two double-gene silencing vectors OsPDS and OsROC5, OsPDS and OsLZAY1, based on pZHY932 backbone vector. Double mutant rice plants with increased leaf and albino tiller angles. And we successfully obtained bladed leaf albino seedling and increased tillering angle albino seedling double-silencing mutations. We further constructed a MIGS-OsGBSS gene silencing vector and obtained rice materials with significantly reduced amylose content. This result indicated that MIGS could be an efficient method in monocots gene silencing and gene function analysis.

Population pharmacokinetic models of lamotrigine in different age groups of Chinese children with epilepsy.

PURPOSE: The study aims to establish population pharmacokinetic (PPK) models of lamotrigine (LTG) in different age groups of epileptic children by nonlinear mixed effect modelling(NONMEM), and provide essential tools and theoretical basis for individualised optimal drug dose. METHODS: Cases of 473 epileptic children were divided into infant, toddler and preschool age (≤6 years) (n = 211), school age (6-12 years) (n = 171) and adolescence age (>12 years) (n = 81). A total of 625 steady-state serum trough concentration samples were extracted. The clinical information included demography, medication, serum concentration data and blood biochemical parameters. PPK models of LTG were established by NONMEM program, using first-order absorption and elimination. Demography and drug combination was investigated for influence on apparent clearance (CL) and apparent volume of distribution (Vd). To assess the accuracy and precision of the different ages and whole-age model, the mean prediction error (MPE), mean absolute error (MAE) and root mean squared error (RMSE) were compared. RESULTS: The final model of LTG in different ages stage and whole age was as follows: (1) infant, toddler and preschool age CL = 0.715 × [(WEIG/16.25)0.655] × (0.458VPA) × (1.99IND), V = 10.4; (2) school age CL(L/h) = 1.01 × (WEIG/30)0.399 × 0.465VPA × 1.98IND, Vd(L) = 17.7; (3) adolescence age CL(L/h) = 1.49 × (WEIG/51.5)0.509 × 0.498VPA × 1.7IND, Vd(L) = 23.1; (4) whole age CL = 0.945 × [(WEIG/25)0.645] × (0.463VPA) × (1.94IND), V = 16.7 × (WEIG/25)0.919 (WEIG, total body weight; VPA, combination with valproate, yes = 1, no = 0; IND, combination with enzyme inducer, yes = 1, no = 0). The values of MPE, MAE and RMSE in age-stage-specific models were less than the ones in the whole-age model, which suggests the age-stage-specific models have better precision and accuracy than the whole-age model. CONCLUSION: PPK models of LTG in different age groups of epileptic children were successfully established. Weight and combination therapy were identified as significant covariates on LTG clearance. Compared with the whole-age model, the age-specific models are more reliable.

Overall condition improvement in a rat model of nephrotic syndrome treated with CellCept nanoliposomes.

Purpose To investigate the effect of CellCept nanoliposomes on Adriamycin-induced nephrotic syndrome in rats. Methods To model nephrotic syndrome, rats were injected with 6.5 mg/kg of Adriamycin in the tail vein. The rats were randomly divided into three groups, including a control group, a free mycophenolate mofetil (MMF)-treated group, and a liposome-encapsulated MMF-treated group. Five weeks after the Adriamycin treatment, the free MMF-treated group received CellCept while the liposome-encapsulated MMF-treated group received the CellCept nanoliposomes for 2 weeks. The general condition of the animals was observed, which included urine volume over 24 h, urine protein levels, and serum biochemical indexes. Renal morphology was also observed. Results The level of urine protein over 24 h was increased in the control group, while plasma albumin (ALB) was decreased. The total cholesterol (TC) and triacylglycerol (TG) levels increased significantly (P < 0.05, P < 0.01). The pathological examination of the kidneys showed some abnormalities. In contrast, these parameters were improved significantly in the free mycophenolate mofetil (MMF)-treated and liposome-contained mycophenolate mofetil (MMF)-treated groups. Conclusion The CellCept nanoliposomes have a good therapeutic effect on Adriamycin-induced nephrotic syndrome in rats.

Expression pattern of G protein­coupled estrogen receptor 1 (GPER) in human cumulus granulosa cells (CGCs) of patients with PCOS.

Estradiol mediates its actions by binding to classical nuclear receptors, estrogen receptor α (ER-α) and estrogen receptor ß (ER-ß), and the non-classical G protein-coupled estrogen receptor 1(GPER). Several gene knockdown models have shown the importance of the receptors for growth of the oocyte and for ovulation. The aim of our study was to identify the pattern of GPER expression in human cumulus granulosa cells (CGCs) from ovarian follicles at different stages of oocyte maturation, and the differences of GPER expression between polycystic ovary syndrome (PCOS) patients and non-PCOS women. Thirty-eight cases of PCOS patients and a control group of thirty-two infertile women without PCOS were used in this study. GPER's location in CGCs was investigated by immunohistochemistry. Quantitative RT-PCR and western blot were used to identify the quantify GPER expression. Here we demonstrated that GPER was expressed in CGCs of both PCOS patients and non-PCOS women, and the expression of GPER was decreased significantly during oocyte maturation. But the expression levels of GPER in CGCs of PCOS patients and non-PCOS women were not significantly different. The data indicate that GPER may play a role during human oocyte maturation through its action in cumulus granulosa cells. ABBREVIATIONS: AMHRIIs: anti-Mullerian hormone type II receptors; BMI: body mass index; CGCs: cumulus granulosa cells; COH: controlled ovarian hyperstimulation; E2: estradiol; EGFR: epidermal growth factor receptor; ER-α: estrogen receptor; ER-ß: estrogen receptor ß; FF: follicular fluid; FSH: follicle-stimulating hormone; GCs: granulosa cells; GPER: G protein-coupled estrogen receptor 1; GV: germinal vesicle; GVBD: germinal vesicle breakdown; HCG: human chorionic gonadotropin; IRS: immunoreactive score; IVF-ET: in vitro fertilization and embryo transfer; MI: metaphase I; MII: metaphase II; MAPK: mitogen-activated protein kinase; OCCCs: oocyte corona cumulus complexes; PCOS: polycystic ovarian syndrome; q RT-PCR: quantitative real-time PCR: qRT-PCR.