Meta-Analysis on the Therapeutic Effect of Transcatheter Arterial Chemoembolization Combined with Portal Vein Embolization.

INTRODUCTION: The aim of the study was to conduct a systematic review to explore the therapeutic effect of transcatheter arterial chemoembolization (TACE) combined with portal vein embolization (PVE) for patients with hepatocellular carcinoma (HCC). METHODS: Chinese and English databases (PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang database, and VIP database) were searched from database inception to August 15, 2023. Studies comparing TACE combined with PVE versus TACE alone for patients with HCC were included. The degree of heterogeneity was assessed using I2 statistics and a Q test. The effect size was represented by risk ratio and mean difference (MD), and the effect size range was estimated using a 95% confidence interval (CI). RESULTS: Eight eligible studies were included in the systematic review, involving 689 participants. The results showed that the future liver residual (FLR) of patients treated with TACE combined with PVE was significantly higher than that of those treated with PVE alone (MD = 3.99%; 95% CI: 1.03-6.94). Furthermore, compared with PVE alone, TACE combined with PVE had a positive effect on disease-free survival (odds ratio [OR] = 2.16; 95% CI: 1.20-3.88), recurrence rate (OR = 0.79; 95% CI: 0.07-9.42), and complications (OR = 0.53; 95% CI: 0.30-0.96). There was no statistically significant impact on mortality with TACE combined with PVE treatment. CONCLUSION: The combination of TACE with PVE can significantly reduce the FLR of patients with HCC, with higher disease-free survival, lower recurrence rate, and fewer complications.

Mono+ algorithm assessment of the diagnostic value of dual-energy CT for high-risk factors for colorectal cancer: a preliminary study.

Background: Risk factors for colorectal cancer (CRC) affect the way patients are subsequently treated and their prognosis. Dual-energy computerized tomography (DECT) is an advanced imaging technique that enables the quantitative evaluation of lesions. This study aimed to evaluate the quality of DECT images based on the Mono+ algorithm in CRC, and based on this, to assess the value of DECT in the diagnosis of CRC risk factors. Methods: This prospective study was performed from 2021 to 2023. A dual-phase DECT protocol was established for consecutive patients with primary CRC. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), overall image quality, lesion delineation, and image noise of the dual-phase DECT images were assessed. Next, the optimal energy-level image was selected to analyze the iodine concentration (IC), normalized iodine concentration (NIC), effective atomic number, electron density, dual-energy index (DEI), and slope of the energy spectrum curve within the tumor for the high- and low-risk CRC groups. A multifactor binary logistic regression analysis was used to construct a differential diagnostic regression model for high- and low-risk CRC, receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was calculated to assess the diagnostic value of the model. Results: A total of 74 patients were enrolled in this study, of whom 41 had high-risk factors and 33 had low-risk factors. The SNR and CNR were best at 40 keV virtual monoenergetic imaging (VMI) based on the Mono+ algorithm (VMI+) (SNR 8.79±1.27, P<0.001; CNR 14.89±1.77, P=0.027). The overall image quality and lesion contours were best at 60 keV VMI+ and 40 keV VMI+, respectively (P=0.001). Among all the DECT parameters, the arterial phase (AP)-IC, NIC, DEI, energy spectrum curve, and venous phase-NIC differed significantly between the two groups. The AP-IC was the optimal DECT parameter for predicting high- and low-risk CRC with AUC, sensitivity, specificity, and cut-off values of 0.96, 97.06%, 87.80%, and 2.94, respectively, and the 95% confidence interval (CI) of the AUC was 0.88-0.99. Integrating the clinical factors and DECT parameters, the AUC, sensitivity, specificity, and predictive accuracy of the model were 0.99, 100.00%, 92.68%, and 94.67%, respectively, and the 95% CI of the AUC was 0.93-1.00. Conclusions: The DECT parameters based on 40 keV noise-optimized VMI+ reconstruction images depicted the CRC tumors best, and the clinical DECT model may have significant implications for the preoperative prediction of high-risk factors in CRC patients.

Gastrodin ameliorates cognitive dysfunction in diabetes by inhibiting PAK2 phosphorylation.

Diabetes is associated with higher prevalence of cognitive dysfunction, while the underlying mechanism is still elusive. In this study, we aim to explore the potential mechanism of diabetes-induced cognitive dysfunction and assess the therapeutic effects of Gastrodin on cognitive dysfunction. Diabetes was induced by a single injection of streptozotocin. The Morris Water Maze Test was employed to assess the functions of spatial learning and memory. Transcriptome was used to identify the potential factors involved. Western blot and immunofluorescence were applied to detect the protein expression. Our results have shown that spatial learning was impaired in diabetic rats, coupled with damaged hippocampal pyramidal neurons. Gastrodin intervention ameliorated the spatial learning impairments and neuronal damages. Transcriptomics analysis identified differential expression genes critical for diabetes-induced hippocampal damage and Gastrodin treatment, which were further confirmed by qPCR and western blot. Moreover, p21 activated kinase 2 (PAK2) was found to be important for diabetes-induced hippocampal injury and its inhibitor could promote the survival of primary hippocampal neurons. It suggested that PAK2 pathway may be involved in cognitive dysfunction in diabetes and could be a therapeutic target for Gastrodin intervention.

Mechanical behavior and reloading reinforcement characteristics of fractured coal under low confining pressure.

To study the basic mechanical behavior and the reloading reinforcement characteristics of fractured coal, conventional triaxial loading tests with different fissure angle were first carried out. On this basis, conventional triaxial loading and unloading tests were conducted to investigate the reloading reinforcement characteristics of fractured coal. The results reveal that when the fissure angle was small, the stress-strain curve exhibited the multi-peak phenomena. As the fissure angle increased, the stress drop phenomenon in the peak region was weakened. With the increase of the fissure angle, the peak stress of the specimens increased and then decreased, while the elastic modulus showed an overall increasing trend, demonstrating the controlling effect of the crack angle. Meanwhile, the cyclic loading exhibited a certain enhancement effect on the strength of the fractured coals when the specimens was unloaded near the crack closure stress. The findings can provide a better understanding of the failure mechanism and reloading reinforcement characteristics of fractured coal.

[Determination of complexation ability of rhubarb with copper ions by ultra-high performance liquid chromatography].

Gandou decoction (GDD) is a traditional Chinese medicine prescription that has been widely used to treat copper metabolism disorders in China with remarkable clinical effect and lower toxicity. However, evaluation of the complexation ability of copper ions is challenging, which hinders screening and discovery of coordinate active ingredients in GDD. An analytical method is needed to determinate the complexation ability of chemical constituents with copper ions. In this study, a rapid and accurate method based on ultra-high performance liquid chromatography (UHPLC) was developed to determine the complexing ability of rhubarb with copper ions. First, the optimal coordination reaction conditions between active ingredients of rhubarb and copper ions were determined. The samples were separated using an Agilent Eclipse Plus C18 column (50 mm×2.1 mm, 1.8 µm) with 5 µL injection volumes. The mobile phase was gradient eluted with methanol and water containing 0.1% (v/v) phosphoric acid at a flow rate of 0.3 mL/min. The detection wavelength was 254 nm and the column temperature was 30 ℃. Under the optimized chromatographic conditions, the rhubarb constituents were effectively separated. Next, peak areas of rhubarb were calculated before and after the coordination reaction between copper ions. The complexing ability of active ingredients in rhubarb with copper ions was evaluated by calculating the rate of changes of their chromatographic peak areas. Finally, ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was used to identify the coordination active ingredients in rhubarb extract. Focusing on the coordination reaction conditions between active ingredients of rhubarb and copper ions revealed that the active ingredients of rhubarb and copper ions reached equilibrium by coordination reaction at pH 9 for 12 h. Methodological evaluation revealed the good stability and repeatability of the method. Under these conditions, 20 major components of rhubarb were identified by UPLC-Q-TOF-MS. According to the coordination rate of each component and copper ions, eight components with strong coordination were screened out (gallic acid 3-O-ß-D-(6'-O-galloyl)-glucopyranoside, aloe emodin-8-O-ß-D-glucoside, sennoside B, l-O-galloyl-2-O-cinnamoyl-glucoside, chysophanol-8-O-ß-D-(6″-O-acetyl)-glucoside, aloe-emodin, rhein and emodin). The respective complexation rates of the components were 62.50%, 29.94%, 70.58%, 32.77%, 34.61%, 26.07%, 28.73% and 31.78%. Compared with other reported methods, the presently developed method can be used to screen the active ingredients of traditional Chinese medicines that have complexing ability with copper ions, especially in complex mixture systems. This study describes an effective detection technology for evaluating and screening the complexing ability of other traditional Chinese medicines with metal ions.

Cerebrospinal fluid findings of infant tuberculous meningitis: a scoping review.

BACKGROUND: Cerebrospinal fluid (CSF) examinations play an important role in the diagnosis of tuberculous meningitis (TBM). However, their yield in the diagnosis of infant TBM remains unclear. This scoping review aims to detail the role of CSF examination for the diagnosis of infant TBM. METHODS: A comprehensive literature search of PubMed, EBSCO, Embase, Scopus, Web of Science, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials was performed to identify articles published prior to October 14th, 2021. Articles describing the results of CSF exanimations among infant TBM were eligible for inclusion. Data extracted from each study included age, sex, CSF microbiological evidence (such as AFB smear, TB PCR, and TB culture), and routine CSF examinations (such as appearance, red blood cell count, white blood cell count, protein, and glucose). RESULTS: A total of 98 cases were included in the final analysis. The yield of microbiological methods was listed as follows: CSF AFB smear, 20.5% (9/44); CSF TB culture 47.5% (29/61); CSF TB PCR, 65.0% (26/40); the combination of them, 57.3% (47/82). According to Marais criteria, the positivities of CSF examinations were calculated as follows: WBC count (ref, 50-500/µL), 65.5% (55/84); lymphocyte predominance (ref, >0.5), 75.4% (49/65); total protein (ref, >100 mg/dL), 67.8% (59/87); glucose (ref, <2.2 mmol/L, or CSF/serum ratio < 0.5), 68.2% (58/85). CONCLUSIONS: Our data demonstrated that routine microbiological tools for infant TBM diagnosis have a sensitivity ranging from 20.5% to 65.0%, and most CSF features are non-specific and insufficient to predict a diagnosis of infant TBM. Therefore, further effort is required to develop new tools for infant TBM diagnosis.Key messages: Routine microbiological tools (such as acid-fast bacilli smear, PCR, and culture) have an unsatisfactory sensitivity for infant TBM diagnosis, and most CSF features are non-specific and insufficient to predict a diagnosis of infant TBM. Therefore, further effort is required to develop new tools for infant TBM diagnosis.

PLCζ can stably regulate Ca2+ fluctuations in early embryo.

Phospholipase C zeta (PLCζ) is an important inducer of Ca2+ oscillations in mammalian sperm. To explore the influence of PLCζ on early embryonic Ca2+ fluctuations during sperm-egg binding, this study used PLCζ from sheep sperm to construct an early embryonic Ca2+ fluctuation model. First, sheep MII oocytes were cultivated and screened using microinjection technology. Then, a pEGFP-N1-PLCζ plasmid was constructed to activate oocytes in the test group. Ionomycin combined with 6-Dimethylaminopurine (6-DMAP) was used for the control group to explore the effects on early embryonic development and regulation of Ca2+ fluctuations during development. The results demonstrated that both the PLCζ and ionomycin combined with 6-DMAP activation methods induced sheep oocyte parthenogenetic activation and development in early embryos. In comparisons, the cleavage rate of ionomycin combined with 6-DMAP activation was significantly higher than that of PLCζ (60.9% ± 19.4% vs 76.1% ± 0.7%, respectively; p < 0.001), and the blastocyst rates were 16.2% ± 0.62% and 21.1% ± 0.92%, respectively (p < 0.05). Additionally, when comparing the distribution of Ca2+ in early embryos at different stages, Ca2+ in both treatment groups was mainly distributed in the cytoplasm, but the temporal pattern of Ca2+ fluctuations differed. PLCζ resulted in Ca2+ peaks that appeared at the cleavage and morula stages of early embryos, and Ca2+ returned to normal levels at the morula stage. However, the Ca2+ concentration after ionomycin combined with 6-DMAP activation was always much higher than that with PLCζ, and its single peak appeared later than in the PLCζ group. In summary, the PLCζ gene promoted stable regulatory effects on Ca2+ fluctuations at different stages during early embryonic development.

The Sensitivity of Diagnostic Criteria of Marais S, et al. in Confirmed Childhood Tuberculous Meningitis.

BACKGROUND: To establish the sensitivity of the diagnostic criteria published by Marais and co-workers in 2010 for childhood tuberculous meningitis (TBM), a retrospective study on children with confirmed TBM was conducted. METHODS: Between January 2006 and December 2019, children consecutively diagnosed with TBM were recruited retrospectively at our center. TBM was defined in cases where any of the following criteria were met: the presence of acid-fast bacilli (AFB) in cerebrospinal fluid (CSF) microscopy, CSF nucleic acid amplification test (NAAT, +), or M.tuberculosis cultured from CSF. The demographic and clinical features of all enrolled patients were recorded including clinical characteristics, CSF findings, cerebral imaging features, and other evidence of TB. RESULTS: A total of 30 children with confirmed diagnosis of TBM over an 14-year period were recruited. The mean age of patients was 7.2 ± 5.1 years and 16 (53.3%) were male. The estimated mean diagnostic score was 12.7 ± 2.4. Twenty-three (76.7%; 95% CI: 59.1-88.2%) patients were classified as "probable TBM" according to the Marais criteria and 7 (23.3%; 95% CI: 11.8-40.9%) as "possible TBM." Further statistical analysis revealed significant differences in CSF scores between probable and possible TBM groups. Other variables reported at a relatively low frequency, such as symptoms and imaging features, made little contribution to TBM diagnosis according to the Marais criteria. CONCLUSION: Childhood TBM could be effectively identified by the criteria defined by Marais et al. However, further revision is required to ensure that the system is more sensitive and easier to perform in practice.

Systematic appraisal of guidelines for the diagnosis of pancreatic cancer.

This review aimed at assessing current guidelines' methodological quality systematically for pancreatic cancer's diagnosis and to reveal the heterogeneity of the recommendations among the evaluated guidelines. A systematic search was conducted to find the latest guidelines for pancreatic cancer's diagnosis. The Appraisal of Guidelines for Research and Evaluation (AGREE II) tool was used to assess the qualified guidelines' feature. We extracted the main recommendations for the diagnosis of pancreatic cancer from the guidelines and performed a heterogeneity evaluation. The highest-level evidence that supported these recommendations was further extracted and analysed. Nine guidelines for the diagnosis of pancreatic cancer were included in this study. Four of the guidelines had an overall score of more than 60% and thus are recommended for clinical use. Further analysis of the heterogeneity of the main recommendations for the diagnosis of pancreatic cancer in the guidelines revealed that the recommendations vary greatly among the different guidelines. The main reasons for the great differences include the neglect of symptoms and signs, great differences in the items involved in recommendations for the diagnosis of pancreatic cancer, inconsistent recommendations for some indicators (carbohydrate antigen 19-9 and ERCP), the unreasonable citation of evidence, and the failure of some recommendations to provide evidence supporting the recommendations. For most recommendations, there was a low level of evidence and a dearth of high-quality study evidence. Recommendations for pancreatic cancer diagnosis have been significantly inconsistent over the past five years. The quality of the guidelines for diagnosing pancreatic cancer also varies. The improvement by the guideline creators of the factors that contribute to the differences mentioned above will be a shortcut to update the guidelines for the diagnosis of pancreatic cancer.

Systematic evaluation of the diagnostic approach of inflammatory bowel disease guidelines.

OBJECTIVE: To collect and evaluate the diagnostic approach of inflammatory bowel disease (IBD) guidelines and provide useful feedback for guideline developers and evidence-based clinical information to help physicians make decisions. METHODS: Diagnostic guidelines for IBD were retrieved by performing systemic and manual searches. Qualified clinical practice guidelines (CPGs) were included and then evaluated by four well-trained evaluators using the AGREE II instrument. To reduce the bias generated in this process, we used the Measurement Scale of Rate of Agreement (MSRA) tool to interpret the results. Guidelines with good recommendation distributions among the diagnostic field were further reclassified and evaluated. RESULTS: Fifteen diagnostic CPGs for IBD were identified and evaluated, and 70.3% (11/15) of the CPGs were above the recommended level. We observed heterogeneity among the diagnostic CPGs for IBD and discrepancies among different domains in one specific guideline. Potential improvements were identified in the fields of stakeholder involvement, rigour of development and applicability. By further analysing the heterogeneity of the recommendations and evidence in 5 UC-CPGs, we found the following issues: no discussion of diagnosing severe complications of UC, disputed significance of serologic and genetic diagnoses of UC, insufficient attention towards medical histories/physical examinations/differential diagnoses and discrepancy in classification criteria. CONCLUSION: The included diagnostic CPGs for IBD were generally of good quality, but heterogeneity was identified. Addressing these issues will provide useful feedback for the guideline updating process, and it will also benefit current clinical practice and eventually patient outcome.

Risk factors for poor outcome in childhood tuberculous meningitis.

Tuberculous meningitis (TBM) remains a serious disease for children and its risk factors of poor outcome remain unclear. Therefore, a retrospective study was conducted aiming to investigate the risk factors associated with poor outcome of childhood TBM. Between January 2006 and December 2019, consecutive children patients (≤ 15 years old) who had a diagnosis of TBM were included for the analysis. The demographic, clinical, laboratory, and radiographic data were collected from the electronic medical records retrospectively. Poor outcome was defined as death or transfer to a higher-level hospital. Patients were then divided into good and poor outcome groups. Subsequently, risk factors for poor outcome were estimated using univariate and multivariate logistic regression analysis. A total of 149 children with TBM was enrolled, twenty-two patients suffered poor outcome, including 16 transfers to a higher-level hospital and 6 deaths, and the remaining 127 patients were classified as good outcome group. Further multivariate analysis revealed that coma (age- and sex-adjusted OR = 6.425, 95% CI: 1.743, 23.676; P < 0.01) and cerebrospinal fluid (CSF) protein (> 1188.3 mg/L; age- and sex-adjusted OR = 4.680, 95% CI: 1.469, 14.902; P < 0.01) were associated with the poor outcome of childhood TBM. Childhood TBM remains to have a high mortality rate in China. High CSF protein and coma were identified as risk factors for poor outcome of childhood TBM. Hence, more attention is required to be paid to suspected patients with such characteristics, thus facilitating access to optimum treatment.

Epidemiological Trends in the Form of Childhood Tuberculosis in a Referral Tuberculosis Hospital in Shandong, China.

BACKGROUND: In China, the prevalence of tuberculosis (TB) diseases and epidemiological trends in the TB forms among children are still unclear; a retrospective study was conducted aiming to assess it. METHODS: Between January 2007 and September 2020, 1577 consecutive childhood TB patients (aged ≤ 15 years) were included in the study. Data, including demographic information and underlying diseases, were collected from medical records. Then, patients were categorized and reported according to the anatomical site of TB disease. To analyze the epidemiological trends in the proportion of each form of TB disease, a linear-by-linear association was used, and a P value of <0.05 was considered to indicate that a significant change had occurred in the proportion of TB disease over the studied period. RESULTS: During the fourteen-year study period, a total of 1577 children patients were enrolled, including 954 boys (60.5%) and 623 girls (39.5%), with a mean age of 9.26 ± 5.18 years. Among the studied patients, 810 (51.4%) patients have pulmonary TB, 1137 (72.1%) have extrapulmonary TB, 372 (23.6%) have both conditions, and another 765 (48.5%) extrapulmonary cases presented in isolated form. Pleural TB (29.0%) and tuberculous lymphadenitis (23.7%) were the most frequent two forms of childhood TB. In addition, during the past decade, the proportions of pulmonary TB, pleural TB, and tuberculous lymphadenitis showed an increasing trend (all P < 0.05). However, no significant trends in the proportions of other forms of TB disease, such as extrapulmonary TB (P > 0.05), tuberculous meningitis (P > 0.05), endobronchial TB (P > 0.05), and disseminated TB (P > 0.05), were found. CONCLUSION: Our findings suggest that childhood TB is facing new challenges, and the policy should be adjusted timely to fit the real situation.

Risk Factors for False-Negative Interferon-γ Release Assay Results in Culture-Confirmed Childhood TB.

A negative interferon-γ release assay (IGRA) result might inappropriately lower the clinical suspicion for childhood tuberculosis (TB) and result in delayed treatment initiation. However, the risk factors associated with false-negative IGRA results in children remain unclear. Between May 2012 and January 2018, 156 culture-confirmed childhood TB patients who had received T-SPOT.TB test were included. Data, including demographic information and clinicopathological variables, were collected via questionnaires. Univariate and multivariate logistic regression analyses were performed to estimate the odds ratio (OR) and corresponding 95% CI of risk factors associated with false-negative T-SPOT.TB results. The positive rate of T-SPOT.TB test was 85.9% in childhood TB patients. Multivariate analysis revealed that younger age (≤ 9 years; OR = 4.782; 95% CI: 1.689, 13.539), weight for age (z-score > 0.37; OR = 4.256; 95% CI: 1.458, 12.428), and hypoproteinemia (total protein ≤ 68.4 g/L; OR = 7.131; 95% CI: 1.864, 27.271) were risk factors for false-negative T-SPOT.TB results in childhood TB. Younger age, overweight, and hypoproteinemia were found to be associated with false-negative T-SPOT.TB results in childhood TB. Health care professionals should consider these risk factors when evaluating suspected childhood TB with negative T-SPOT.TB results.

Early intervention with gastrodin reduces striatal neurotoxicity in adult rats with experimentally­induced diabetes mellitus.

Glutamate­induced excitotoxicity in the striatum has an important role in neurodegenerative diseases. It has been reported that diabetes mellitus (DM) induces excitotoxicity in striatal neurons, although the underlying mechanism remains to be fully elucidated. The present study aimed to investigate the effect of gastrodin on DM­induced excitotoxicity in the striatal neurons of diabetic rats. Adult Sprague­Dawley rats were divided into control, diabetic, and gastrodin intervention groups. Diabetes in the rats was induced with a single intraperitoneal injection of streptozotocin (65 mg/kg). In the gastrodin groups, the rats were gavaged with 60 or 120 mg/kg/day gastrodin for 6 weeks, 3 weeks following the induction of diabetes. Pathological alterations in the striatum were assessed using hematoxylin and eosin (H&E) staining. The protein expression levels of phosphorylated (p)­extracellular signal­regulated kinase (ERK)1/2, p­mitogen­activated protein kinase kinase (MEK)1/2, tyrosine receptor kinase B (TrKB) and brain­derived neurotrophic factor (BDNF) in the striatal neurons were evaluated by western blotting and double immunofluorescence. Additionally, the extracellular levels of glutamate were measured by microanalysis followed by high­pressure­liquid­chromatography. In diabetic rats, striatal neuronal degeneration was evident following H&E staining, which revealed the common occurrence of pyknotic nuclei. This was coupled with an increase in glutamate levels in the striatal tissues. The protein expression levels of p­ERK1/2, p­MEK1/2, TrKB and BDNF in the striatal tissues were significantly increased in the diabetic rats compared with those in the normal rats. In the gastrodin groups, degeneration of the striatal neurons was ameliorated. Furthermore, the expression levels of glutamate, p­ERK1/2, p­MEK1/2, TrKB and BDNF in the striatal neurons were decreased. From these findings, it was concluded that reduced neurotoxicity in striatal neurons following treatment with gastrodin may be attributed to its suppressive effects on the expression of p­ERK1/2, p­MEK1/2, BDNF and TrKB.

Expression Changes of NMDA and AMPA Receptor Subunits in the Hippocampus in rats with Diabetes Induced by Streptozotocin Coupled with Memory Impairment.

Cognitive impairment in diabetes (CID) is a severe chronic complication of diabetes mellitus (DM). It has been hypothesized that diabetes can lead to cognitive dysfunction due to expression changes of excitatory neurotransmission mediated by N-methyl-D-aspartate receptors (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR); however, the pathogenesis involved in this has not been fully understood, especially at early phase of DM. Here, we sought to determine the cognitive changes and aim to correlate this with the expression changes of NMDAR and AMPAR of glutamate signaling pathways in the rat hippocampus from early phase of DM and in the course of the disease progression. By Western blot analysis and immunofluorescence labeling, the hippocampus in diabetic rats showed a significant increase in protein expression NMDAR subunits NR1, NR2A and NR2B and AMPAR subunit GluR1. Along with this, behavioral test by Morris water maze showed a significant decline in their performance when compared with the control rats. It is suggested that NR1, NR2A, NR2B and GluR1are involved in learning and memory and that their expression alterations maybe correlated with the occurrence and development of CID in diabetic rats induced by streptozotocin.

MiR-448-5p inhibits TGF-ß1-induced epithelial-mesenchymal transition and pulmonary fibrosis by targeting Six1 in asthma.

MicroRNAs (miRNAs) are small yet versatile gene tuners that regulate a variety of cellular processes, including cell growth and proliferation. The aim of this study was to explore how miR-448-5p affects airway remodeling and transforming growth factor-ß1 (TGF-ß1)-stimulated epithelial-mesenchymal transition (EMT) by targeting Sine oculis homeobox homolog 1 (Six1) in asthma. Asthmatic mice models with airway remodeling were induced with ovalbumin solution. MiRNA expression was evaluated using quantitative real-time polymerase chain reaction. Transfection studies of bronchial epithelial cells were performed to determine the target genes. A luciferase reporter assay system was applied to identify whether Six1 is a target gene of miR-448-5p. In the current study, we found that miR-448-5p was dramatically decreased in lung tissues of asthmatic mice and TGF-ß1-stimulated bronchial epithelial cells. In addition, the decreased level of miR-448-5p was closely associated with the increased expression of Six1. Overexpression of miR-448-5p decreased Six1 expression and, in turn, suppressed TGF-ß1-mediated EMT and fibrosis. Next, we predicted that Six1 was a potential target gene of miR-448-5p and demonstrated that miR-448-5p could directly target Six1. An SiRNA targeting Six1 was sufficient to suppress TGF-ß1-induced EMT and fibrosis in 16HBE cells. Furthermore, the overexpression of Six1 partially reversed the protective effect of miR-448-5p on TGF-ß1-mediated EMT and fibrosis in bronchial epithelial cells. Taken together, the miR-448-5p/TGF-ß1/Six1 link may play roles in the progression of EMT and pulmonary fibrosis in asthma.

Establishment of rat pneumococcal meningitis models: a histopathological analysis.

The aim of this study was to perform a preliminary investigation of the pathogenesis of bacterial meningitis-induced brain injury by establishing rat pneumococcal meningitis models. Infant Wistar rats were intracranially inoculated with different concentrations of Streptococcus pneumoniae. Rats were sacrificed at different time points to observe clinical symptoms and pathological changes in brain tissues. Twenty-four hours after intracranial inoculation with Streptococcus pneumoniae, regardless of high or low concentrations of bacterial inoculation, all rats developed bacterial meningitis with manifestations such as lethargy and seizures. Pathological changes in brain tissues included subarachnoid and intraventricular inflammation, vasodilation and vascular congestion, and cortical neuronal necrosis. The number of rats with seizures, the degree of cerebral vascular disease, and the extent of neuronal damage were associated with the concentration of bacterial inoculum. Thirty days after infection, brain tissue weight significantly reduced. The pathological changes induced by inoculation with pneumococcal meningitis in Wistar rats were similar to those seen in the human brain. The possible mechanisms of brain damage caused by meningitis are cerebrovascular inflammation and disruption of regional cerebral blood flow.

[Preparation of a glypican-3-targeting hepatocellular carcinoma MR probe and its molecular imaging in HepG2 cells].

OBJECTIVE: To prepare a glypican-3 (GPC3)-targeting hepatocellular carcinoma MR molecular probe and to evaluate its targeting specificity using HepG2 cells. METHODS: Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared by a double emulsion solvent evaporation method, and the surfaces were connected with anti-GPC3 mono-antibody and paramagnetic substance Gd3+. The physical properties of the probes were investigated using fluorescence microscopy, electron microscopy, Malvern particle size analysis, inductively coupled plasma atomic emission spectroscopy (ICP-AES) and 1.5T MR imaging. The specificity of the probes to target cultured HepG2 cells was determined by laser confocal microscopy. The signal characteristics, including signal-to-noise ratio (SNR), after co-incubation with HepG2 cells were analyzed by 1.5T MR imaging. Significance of differences between multiple groups (target group, non-target group, and control group) was assessed by one-way analysis of variance, and between two groups was assessed by the LSD-t test. A difference was considered to be statistically significant at P less than 0.05. RESULTS: The GPC3-targeting hepatocellular carcinoma MR molecular probes were successfully prepared. The nanoparticles had a spherical shape, size of 495 +/- 17.5 nm, uniform size distribution, good dispersibility, no obvious aggregation, and could significantly increase the T1 signal. Using the ICP-AES measurement, 1 mol PLGA carried about 12 mol Gd3+, and as the Gd3+ concentration increased, the T1 signal increased. The prepared MR molecular probes could specifically target HepG2 cells, and could increase the T1 signal. The SNR value of the target group was 3.45 +/- 0.21, of the non-target group was 1.43 +/- 0.07, and of the control group was 1.12 +/- 0.03. The SNR value of the target group was significantly higher than that of the non-target group and the control group (P less than 0.05); there was no significant difference between the non-target group and the control group (P more than 0.05). CONCLUSION: PLGA nanoparticles, anti-GPC3 mono-antibody and paramagnetic Gd3+ can be used to successfully prepare GPC3-targeting hepatocellular carcinoma MR molecular probes which are capable of specifically targeting HepG2 cells in vitro and being detected by 1.5T MR imaging. These MR molecular probes may represent a useful noninvasive imaging method for detecting early hepatocellular carcinoma in vivo.

Cytotoxicity, genotoxicity, and mutagenicity of 1-chloro-2-hydroxy-3-butene and 1-chloro-3-buten-2-one, two alternative metabolites of 1,3-butadiene.

The cytotoxicity, genotoxicity, and mutagenicity of 1-chloro-2-hydroxy-3-butene (CHB), a known in vitro metabolite of the human carcinogen 1,3-butadiene, have not previously been investigated. Because CHB can be bioactivated by alcohol dehydrogenases to yield 1-chloro-3-buten-2-one (CBO), a bifunctional alkylating agent that caused globin-chain cross-links in erythrocytes, in the present study we investigated the cytotoxic and genotoxic potential of CHB and CBO in human normal hepatocyte L02 cells using the MTT assay, the relative cloning efficiency assay and the comet assay. We also investigated the mutagenic potential of these compounds with the Ames test using Salmonella strains TA1535 and TA1537. The results provide clear evidence for CHB and CBO being both cytotoxic and genotoxic with CBO being approximately 100-fold more potent than CHB. Interestingly, CHB generated both single-strand breaks and alkali-labile sites on DNA, whereas CBO produced only alkali-labile sites. CHB did not directly result in DNA breaks, whereas CBO was capable of directly generating breaks on DNA. Interestingly, both compounds did not induce DNA cross-links as examined by the comet assay. The Ames test results showed that CHB induced point mutation but not frameshift mutation, whereas the toxic effects of CBO made it difficult to reliably assess the mutagenic potential of CBO in the two strains. Collectively, the results suggest that CHB and CBO may play a role in the mutagenicity and carcinogenicity of 1,3-butadiene.