Attention deficit hyperactivity disorder in children with epilepsy: a multicenter cross-sectional analysis in China.

BACKGROUND: The diagnosis and treatment of attention deficit hyperactivity disorder (ADHD) comorbid with epilepsy have been insufficiently addressed in China. We conducted a study in China to investigate the current status, diagnosis, and treatment of ADHD in children to further our understanding of ADHD comorbid with epilepsy, strengthen its management, and improve patients' quality of life. METHODS: We carried out a multicenter cross-sectional survey of children with epilepsy across China between March 2022 and August 2022. We screened all patients for ADHD and compared various demographic and clinical factors between children with and without ADHD, including gender, age, age at epilepsy onset, duration of epilepsy, seizure types, seizure frequency, presence of epileptiform discharges, and treatment status. Our objective was to explore any possible associations between these characteristics and the prevalence of ADHD. RESULTS: Overall, 395 epilepsy patients aged 6-18 years were enrolled. The age at seizure onset and duration of epilepsy ranged from 0.1-18 to 0.5-15 years, respectively. Focal onset seizures were observed in 212 (53.6%) patients, while 293 (76.3%) patients had epileptiform interictal electroencephalogram (EEG) abnormalities. Among the 370 patients treated with anti-seizure medications, 200 (54.1%) had monotherapy. Although 189 (47.8%) patients had ADHD, only 31 received treatment for it, with the inattentive subtype being the most common. ADHD was more common in children undergoing polytherapy compared to those on monotherapy. Additionally, poor seizure control and the presence of epileptiform interictal EEG abnormalities may be associated with a higher prevalence of ADHD. CONCLUSIONS: While the prevalence of ADHD was higher in children with epilepsy than in normal children, the treatment rate was notably low. This highlights the need to give more importance to the diagnosis and treatment of ADHD in children with epilepsy.

Prognostic Factors for Patients with Proliferative Hepatocellular Carcinoma After Liver Resection.

Purpose: There is a scarcity of predictive models currently accessible for prognosticating proliferative hepatocellular carcinoma (HCC), an integrated class of subtype, characterized by a dismal prognosis. Consequently, this study aimed to develop and validate a novel prognostic model capable of accurately predicting the prognosis of proliferative HCC after curative resection. Patients and Methods: This retrospective multicenter study included patients with solitary HCC who underwent curative liver resection from August 2014 to December 2020 (n = 816). Patients were stratified into either the proliferative HCC cohort (n = 259) or the nonproliferative HCC cohort (n = 557) based on histological criteria. Disease-free survival (DFS) was compared between the two groups before and after one-to-one propensity score matching (PSM). Of all the proliferative HCC patients, 203 patients were assigned to training cohort, and 56 patients were assigned to validation cohort. Univariate and multivariate analyses were performed in training cohort to identify risk factors associated with worse DFS. Thereafter, a predictive model was constructed, subsequently validated in the validation cohort. Results: The DFS of proliferative HCC was significantly worse than nonproliferative HCC before and after PSM. Meanwhile, multivariate regression analysis revealed that liver cirrhosis (P = 0.032) and larger tumor size (P = 0.000) were independent risk factors of worse DFS. Lastly, the discriminative abilities of the predictive model for 1, 3, 5-year DFS rates, as determined by receiver operating characteristic (ROC) curves, were 0.702, 0.720, and 0.809 in the training cohort and 0.752, 0.776, and 0.851 in the validation cohort, respectively. Conclusion: This study developed a predictive model with satisfactory accuracy to predict the worse DFS in proliferative HCCs after liver resection. Moreover, this predictive model may serve as a valuable tool for clinicians to predict postoperative HCC recurrence, thereby enabling them to implement early preventative strategies.

Preoperative Systemic Immune-Inflammation Index is a Potential Biomarker in Adult Patients with High-Grade Gliomas Undergoing Radical Resection.

Background: Increasing evidence has highlighted that systemic immune-inflammation index (SII), a recently developed prognostic biomarker that utilizes peripheral platelet, lymphocyte and neutrophil counts, is associated with unfavorable prognosis in various tumors. Nevertheless, the prognostic significance of SII in high-grade gliomas patients undergoing radical resection remains unclear. Therefore, the present study aimed to assess the potential of SII as a prognostic biomarker in this patient population. Methods: A total of 111 adult patients with high-grade gliomas who underwent radical resection were consecutively enrolled in this investigation. The study involved the categorization of patients into high and low SII groups using predetermined cut-off values. Subsequently, forward stepwise logistic regression was employed to identify autonomous predictors for early gliomas recurrence. To mitigate the impact of confounding factors, a propensity score matching (PSM) analysis was performed between high and low SII patients. Finally, the Kaplan-Meier approach was utilized to compare the progression-free survival (PFS) and overall survival (OS) of the two groups. Results: The study involved the categorization of patients into two groups based on their SII levels, namely high SII (> 604.8) and low SII (≤ 604.8) groups. Forward stepwise logistic regression revealed that high SII (p < 0.001) and tumor size ≥ 50 mm (p < 0.001) were significantly related to early recurrence of gliomas. Furthermore, the results indicate that PFS and OS were significantly shorter in the high SII group compared to the low SII group, both before and after PSM (p < 0.05). Conclusion: Preoperative biomarker SII can serve as a prognostic biomarker for early recurrence and prognosis in patients with high-grade gliomas undergoing radical resection. Furthermore, the combination of tumor size and SII demonstrates a robust predictive capacity for early recurrence and prognosis in this patient population.

[Mechanism of Shenling Baizhu Powder in alleviation of ulcerative colitis in mice based on high-throughput transcriptome sequencing].

High-throughput transcriptome sequencing was used to study the mechanism of Shenling Baizhu Powder(SLBZP) in the alleviation of the dextran sulfate sodium(DSS)-induced ulcerative colitis(UC) in mice. The mouse model of DDS-induced UC was treated with SLBZP by gavage. The changes in general state, disease activity index(DAI), and colon length were observed. The hematoxylin-eosin(HE) staining was used to observe the pathological changes in the colon tissues of mice. Enzyme-linked immunosorbent assay(ELISA) was used to determine the expression levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1ß, IL-6, IL-4, and IL-10 in the serum and tissues of mice. The differentially expressed genes in the control group, the model group, and the SLBZP group were analyzed by high-throughput transcriptome sequencing, and the Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were conducted on the differentially expressed genes. The results showed that after intragastric administration of SLBZP, the symptoms of diarrhea and bloody stool were improved, and the disease active index(DAI) score was reduced. SLBZP effectively reduced the inflammatory cell infiltration and goblet cell loss in the colonic mucosal tissue, reduced the levels of TNF-α, IL-1ß, IL-6 in the serum and colon tissue, and increased the levels of IL-4 and IL-10 in the serum and colon tissue. There were 25 differential genes in SLBZP vs the model group, which were significantly enriched in immune response, immune system process, immunoglobulin production, and other biological processes. KEGG pathway analysis showed that the differential genes were enriched in signaling pathways such as neomycin, kanamycin, and gentamicin biosynthesis, cytokine-cytokine receptor interaction, primary immunodeficiency, and IgA synthesis of the intestinal immune network. This study shows that SLBZP may alleviate UC through immune regulation.

Generation of an integration-free induced pluripotent stem cell line (LZUSHI001-A) from an epileptic patient with DGKG mutation.

Epilepsy is a common chronic neurological disorder related to genetic factors. Base on the non-integrating episomal vector technique, a human induced pluripotent stem cell (iPSC) line, termed as LZUSHI001-A, was generated from peripheral blood mononuclear cells (PBMCs) of a 11-year-old male patient with Epilepsy, who had a heterozygous (c.2042G>A, p.R681Q) mutation in the DGKG gene. LZUSHI001-A offers a useful resource to investigate pathogenic mechanisms in epilepsy, as well as a cell-based model for drug development to treat epilepsy.

Judgement of the Clinical Value of Spiral CT Three-Dimensional Reconstruction in the Diagnosis of Lumbar Degenerative Osteoporosis.

With the aging of the population, there are more and more degenerative diseases of the lumbar spine that accompany osteoporosis. Lumbar degenerative osteoporosis has also become fragile and high in incidence, which has also attracted the attention of experts and scientists in related fields. Degeneration of the lumbar spine often causes pain in the waist and surrounding patients and even affects their life safety. The lesions such as the shoulders and lower back often show varying degrees of softening or induration in the fracture line or osteoporosis will directly produce adverse reactions to joint activities and then cause the development and deterioration of various complications. At present, spiral CT three-dimensional reconstruction technology has been widely used in the field of medical imaging and has played a very important role in the diagnosis and treatment of some diseases. Therefore, combined with three-dimensional reconstruction of spiral CT, this paper discusses its clinical value in the diagnosis of lumbar degenerative osteoporosis. In this experiment, in order to understand the image results after three-dimensional reconstruction, five groups of cases were selected for testing. The test items include the whole lesion site, vertebral imaging, soft tissue lesion site, and lumbar lesion site. In addition, in order to understand the clinical value of spiral CT three-dimensional reconstruction in the diagnosis of lumbar degenerative osteoporosis, this technique was compared and tested with other imaging methods. The selected imaging methods include X-ray, CT, and MRI. The test items include sensitivity, accuracy, positive predictive value, and negative predictive value. To explore the clinical value of spiral CT three-dimensional reconstruction in the diagnosis of lumbar degenerative osteoporosis, from the experimental results, the relevant image clarity and accuracy of the five groups of cases are high, the image quality after three-dimensional reconstruction is good, and the clarity and accuracy are high. In addition, the sensitivity and accuracy of spiral CT three-dimensional reconstruction are higher than those of other imaging methods. It has great clinical value in the diagnosis and treatment of lumbar degenerative osteoporosis.

Intraarterial Lidocaine Administration for Pain Control by Water-in-Oil Technique in Transarterial Chemoembolization: in vivo and Randomized Clinical Trial.

OBJECTIVE: To investigate the sustained release of lidocaine from a lidocaine-epirubicin-lipiodol emulsion created by water-in-oil (W/O) technique in vivo and evaluate the efficacy and safety of intraarterial lidocaine administration for intra- and postoperative pain control in transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). METHODS: The in vivo concentrations of lidocaine were determined in tumor tissues after VX2 rabbit models for hepatic tumor were administered with intra-arterial lidocaine-epirubicin-lipiodol emulsion. A prospective randomized controlled clinical trial was performed, enrolling 70 consecutive patients who underwent TACE. Patients were randomized into two groups: Group A received an immediate bolus intraarterial lidocaine injection before TACE, and Group B received a lidocaine-epirubicin-lipiodol emulsion during TACE. Pain intensity was compared between the two groups using a visual analog scale (VAS) score before (Tbefore) and at 0 h (T0), 4 h (T4), 8 h (T8), 24 h (T24), 48 h (T48), and 72 h (T72) after the procedure. Adverse events and intake of analgesics were evaluated and compared between the two groups. RESULTS: The concentrations of lidocaine in tumor tissues were higher in experimental group than in control group at T0.5 (P=0.004), T1 (P=0.038), T4 (P=0.036), and T8 (P=0.029). In the clinical trial, VAS scores in Group B were significantly lower than in Group A at T0 (P=0.006), T4 (P=0.001), T8 (P=0.002), and T24 (P=0.005). The tramadol intake in Group B was significantly lower than in Group A (P=0.021). No significant difference was observed regarding the incidence of adverse events between the two groups. CONCLUSION: This study demonstrated the effectiveness and safety of intraarterial lidocaine administration using the W/O technique in controlling intra- and post-TACE pain.

Systemic Inflammation Response Index is a Prognostic Risk Factor in Patients with Hepatocellular Carcinoma Undergoing TACE.

BACKGROUND: Mounting evidence has shown that systemic inflammation response index (SIRI), a novel prognostic biomarker based on peripheral lymphocyte, neutrophil and monocyte counts, is associated with poor prognosis for several tumors. However, the prognostic value of SIRI in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is elusive. Herein, we aimed to evaluate the correlation between SIRI and clinical outcomes in these patients. METHODS: A total of 194 consecutive patients who underwent TACE were included in this study. Patients were stratified into high and low SIRI groups based on the cut-off value using receiver operating characteristic (ROC) analysis. Independent risk factors for tumor response were analyzed using forward stepwise logistic regression. A one-to-one propensity score matching (PSM) was conducted to compare progression-free survival (PFS) and overall survival (OS) between low and high SIRI patients. The discriminatory power of the combination of number of tumors and SIRI in predicting initial TACE response was evaluated by ROC analysis. RESULTS: Patients were divided into high SIRI (> 0.88) and low SIRI (≤ 0.88) groups. High SIRI (p = 0.003) and more than three tumors (p = 0.002) were significantly related to poorer tumor response. Moreover, the low SIRI group had longer PFS and OS than the high SIRI group (both P < 0.05) before and after PSM. Combination of SIRI and number of tumors can improve the predictive ability to predict initial TACE response with an area under the curve (AUC) of 0.678. CONCLUSION: Pretreatment peripheral blood SIRI was found to be an independent predictor of tumor response and clinical outcomes in patients with HCC undergoing TACE. Patients with high SIRI may have a poor prognosis.

Development and Validation of a Predictive Model for Early Refractoriness of Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma.

Objectives: To develop and validate a predictive model for early refractoriness of transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Methods: In this multicenter retrospective study, a total of 204 consecutive patients who initially underwent TACE were included. Early TACE refractoriness was defined as patients presented with TACE refractoriness after initial two consecutive TACE procedures. Of all patients, 147 patients (approximately 70%) were assigned to a training set, and the remaining 57 patients (approximately 30%) were assigned to a validation set. Predictive model was established using forward stepwise logistic regression and nomogram. Based on factors selected by logistic regression, a one-to-one propensity score matching (PSM) was conducted to compare progression-free survival (PFS) between patients who were present or absent of early TACE refractoriness. PFS curve was estimated by Kaplan-Meier method and compared by log-rank test. Results: Logistic regression revealed that bilobar tumor distribution (p = 0.002), more than three tumors (p = 0.005) and beyond up-to-seven criteria (p = 0.001) were significantly related to early TACE refractoriness. The discriminative abilities, as determined by the area under the receiver operating characteristic (ROC) curve, were 0.788 in the training cohort and 0.706 in the validation cohort. After PSM, the result showed that patients who were absent of early TACE refractoriness had a significantly higher PFS rate than those of patients who were present (p < 0.001). Conclusion: This study presents a predictive model with moderate accuracy to identify patients with high risk of early TACE refractoriness, and patients with early TACE refractoriness may have a poor prognosis.

A predictive model of incomplete response after transarterial chemoembolization for early or intermediate stage of hepatocellular carcinoma: consideration of hepatic angiographic and cross-sectional imaging.

OBJECTIVES: The purpose of the present study is to develop a predictive model for incomplete response (IR) after conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma (HCC) based on hepatic angiographic and cross-sectional imaging. METHODS: Sixty patients with 139 target HCC lesions who underwent cTACE from February 2013 to March 2019 were included in this retrospective study. Hepatic angiographic features were identified: the number of feeding arteries, vascularity of the tumor, tumor staining on angiography, vascular lake phenomenon, and hepatic arterio-portal shunt. Cross-sectional imaging features were also identified: tumor extent, location, size, and enhancement pattern. Treatment response was assessed by the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Logistic regression analysis was performed to determine the potential predictive factors for treatment response. To validate the predictive value of potential factors, the means of a decision tree were also calculated by Classification and Regression Tree (CART). P < 0.05 was considered statistically significant. RESULTS: The IR rate was 43.2% (60/139) in the entire study population. Logistic regression analysis showed that a tumor size > 50 mm (P = 0.005; odds ratio, 7.25; 95% CI 1.79-29.33), central location (P = 0.007; odds ratio, 0.14; 95% CI 0.03-0.59), and nondense tumor staining (P < 0.001; odds ratio, 0.08; 95% CI 0.02-0.28) were predictors of IR after cTACE. Decision tree analysis showed a good ability to classify treatment response with an accuracy of 78.4%. CONCLUSION: Tumor size > 50 mm, central tumor location, and nondense tumor staining were predictors of IR after cTACE. These factors should be taken into consideration when performing cTACE.

Determination of Risk Factors for Pain After Transarterial Chemoembolization with Drug-Eluting Beads for Hepatocellular Carcinoma.

PURPOSE: To identify risk factors for pain after transarterial chemoembolization with drug-eluting beads (DEB-TACE) for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: In this retrospective study, a total of 118 consecutive patients who underwent DEB-TACE between June 2016 and May 2019 with post-TACE pain were included. The patients were divided into three groups based on the severity of post-TACE pain according to the distribution of pain Visual Analogue Scale/Score (VAS). Potential risk factors for post-TACE pain were primarily analyzed using the chi-square test, one-way analysis of variance, or Kruskal-Wallis test (if appropriate). For multivariate analysis, an ordinal logistic regression model was utilized. Variables with P<0.10 in the univariate analysis were included in a multivariate model to identify independent risk factors for post-TACE pain. A multivariate analysis was also performed by means of a decision tree using the Classification and Regression Tree (CART) algorithm. RESULTS: The univariate analysis showed that elderly patients or patients with portal venous tumor thrombus (PVTT) were more likely to have severe post-TACE pain than young patients or those without PVTT (P=0.028 and <0.001, respectively). However, in the ordinal logistic regression, nonsuperselective chemoembolization and presence of PVTT were independent risk factors of severe post-TACE pain (P=0.046 and <0.001, respectively). In addition, the CART showed that nonsuperselective chemoembolization and PVTT could increase the probability of severe post-TACE pain. CONCLUSION: Nonsuperselective chemoembolization and PVTT are independent risk factors for pain after DEB-TACE. Therefore, these factors should be taken into full consideration for the relief of pain.

Ginsenoside Rg1 promotes neural differentiation of mouse adipose-derived stem cells via the miRNA-124 signaling pathway.

We have explored the role of ginsenoside Rg1 in promoting the differentiation of mouse adipose-derived stem cells (mADSC) towards the neuronal lineage. The central nervous system has long been regarded as incapable of self-repair; therefore neuronal differentiation from stem cells is of great interest. However, the use of embryonic stem cells is limited due to their inaccessibility and for ethical reasons, so the search is on for alternative pluripotent cells capable of differentiating into neuronal cells. Adipose-derived stem cells (ADSC) can differentiate into different cell types, including neuronal cells: their accessibility, low risk, and capacity for long-term growth and self-renewal have made them the preferred stem cell type for clinical applications. Several methods have been indicated for promoting the neuronal differentiation of ADSC, but the mechanism of this process has not been clearly identified. As our previous study showed that microRNA-124 (miRNA-124) plays a positive role in promoting the neural differentiation of ADSC, we wanted to find reagents that can upregulate miRNA-124 expression during neural differentiation.

Interaction between nitric oxide signaling and gap junctions during ischemic preconditioning: Importance of S-nitrosylation vs. protein kinase G activation.

Much effort has been dedicated to exploring the mechanisms of IPC, and the GJ is one of the proposed targets of IPC. Several lines of evidence have indicated that NO affects GJ permeability regulation and expression of connexin isoforms. NO-induced stimulation of the sGC-cGMP pathway and the subsequent PKG activation could lead directly to connexin phosphorylation and GJ coupling modification. Additionally, because NO-induced cardioprotection against I/R injury beyond the cGMP/PKG-dependent pathway has been reported in isolated cardiomyocytes, it has been posited that NO-mediated GJ coupling might be independent from the activation of the NO-induced cGMP/PKG pathway during IPC. S-nitrosylation by NO exerts a major influence in IPC-induced cardioprotection. It has been suggested that NO-mediated cardioprotection during IPC was not dependent on sGC/cGMP/PKG but on SNO signaling. We need more researches to prove that which signaling pathway (S-nitrosylation or protein kinase G activation) is the major one modulating GJ coupling during IPC. The aim of review article is to discuss the possible signaling pathways of NO in regulating GJ during IPC.

Electroclinical aspects and therapy of Han patients with juvenile myoclonic epilepsy in northern China.

OBJECTIVE: The objective of this study was to assess the electroclinical aspects and treatment of Han patients with juvenile myoclonic epilepsy (JME) in northern China. METHODS: One hundred fifty-six outpatients with JME from six epilepsy centers, between January 2011 and June 2012, were followed up for at least two years. They underwent twenty-four-hour video-EEG recording. Brain imaging was performed using magnetic resonance imaging (MRI). Clinical aspects, electroencephalographic (EEG) features, and antiepileptic drugs (AEDs) received were reviewed. RESULTS: Generalized tonic-clonic seizures (GTCS) were found in 150/156 patients. Delay of diagnosis was 4.60±9.92years. Photosensitivity was more common in eye closure condition during IPS in patients with JME; in addition, patients with JME with myoclonic seizures (MS) and GTCS as seizure types were likely to present photoparoxysmal responses (PPRs). The 82 nontreated patients showed a median latency to first interictal or ictal generalized spike-wave discharge (GSWD) of 50min (IQR: 22-102min). The first GSWDs were recorded in 63%, 76%, 90%, and 98% patients within one, two, three, and 4h, respectively; only 2% of patients had first GSWDs after 4h. One hundred eleven patients (111/156) chose extended-release valproate (VPA) at daily doses ≤1000mg. The percentages of seizure-free patients among MS, GTCS, and absence seizure (AS) groups were 88.3%, 99.0%, and 94.9%, respectively. CONCLUSION: Photoparoxysmal responses were more common in patients with JME with MS and GTCS and rare in patients with JME with MS and AS in northern Chinese Han patients. Most patients with JME in northern China chose VPA as first therapeutic choice, and low dose (500 to 1000mg daily) of extended-release VPA may be an optimal choice for them. Video-EEG monitoring for at least 4h may be helpful in detecting the first interictal or ictal GSWD in patients with potential JME. Moreover, video-EEG monitoring performed at about 9 o'clock in the morning with patients in the awake state might be useful to find the first GSWD. For JME diagnosis, Class II criteria are more helpful than Class I counterparts, the latter yielding more missed diagnoses.

Relationship Between the Serum Total Bilirubin and Inflammation in Patients With Psoriasis Vulgaris.

BACKGROUND: Psoriasis is a chronic and recurrent inflammatory skin disease. Previous studies have shown that bilirubin has anti-inflammation and antioxidant effects. However, the various roles of bilirubin in psoriasis patients are still unclear. OBJECTIVE: To investigate the serum total bilirubin (TB) level in the individuals with psoriasis vulgaris and further evaluate the relationship between serum TB concentration and C-reactive protein (CRP) to clarify the effect of bilirubin on inflammation. METHODS: A total of 214 patients with psoriasis vulgaris and 165 age- and gender-matched healthy control subjects were recruited. The peripheral leukocyte count (white blood cell, WBC) and differential, serum biochemical and immunologic indexes including serum TB, immunoglobulin (Ig) G, IgA, IgM, complement C3 and C4 , as well as serum CRP concentrations were measured. RESULTS: Results showed that the serum TB level decreased significantly and peripheral WBC, neutrophil, and serum CRP concentrations increased significantly in patients with psoriasis vulgaris. Meanwhile, the serum CRP was negatively correlated with serum TB levels but positively correlated with peripheral WBC and the Psoriasis Area and Severity Index (PASI). Logistic regression analysis showed that the serum TB was a protective factor for psoriasis vulgaris. CONCLUSION: The present study suggests that lower serum TB is associated with the enhancement of the inflammatory response in psoriasis vulgaris. Therefore, lower serum TB has a prognostic significance for worsening psoriasis vulgaris. Bilirubin may play a crucial role in inflammation by contributing to the inhibition of the inflammatory response.

Brazilin plays an anti-inflammatory role with regulating Toll-like receptor 2 and TLR 2 downstream pathways in Staphylococcus aureus-induced mastitis in mice.

Mastitis, which commonly occurs during the postpartum period, is caused by the infection of the mammary glands. The most common infectious bacterial pathogen of mastitis is Staphylococcus aureus (S. aureus) in both human and animals. Brazilin, a compound isolated from the traditional herbal medicine Caesalpinia sappan L., has been shown to exhibit multiple biological properties. The present study was performed to determine the effect of brazilin on the inflammatory response in the mouse model of S. aureus mastitis and to confirm the mechanism of action involved. Brazilin treatment was applied in both a mouse model and cells. After brazilin treatment of cells, Western blotting and qPCR were performed to detect the protein levels and mRNA levels, respectively. Brazilin treatment significantly attenuated inflammatory cell infiltration and inhibited the expressions of TNF-α, IL-1ß and IL-6 in a dose-dependent manner. Administration of brazilin in mice suppressed S. aureus-induced inflammatory injury and the production of proinflammatory mediators. This suppression was achieved by reducing the increased expression of TLR2 and regulating the NF-κB and MAPK signaling pathways in the mammary gland tissues and cells with S. aureus-induced mastitis. These results suggest that brazilin appears to be an effective drug for the treatment of mastitis and may be applied as a clinical therapy.

Tonic modulation of nociceptive behavior and allodynia by cannabinoid receptors in formalin test in rats.

Cannabinoids produce anti-nociceptive and anti-hyperalgesic effects in acute, inflammatory and neuropathic pain models. The current study investigated the role of cannabinoid (CB1 and CB2) receptors in modulating formalin-induced nociceptive behavior and mechanical allodynia in the rat. Rats received subcutaneous plantar injections of 5% formalin in the hind paws. Licking, biting and paw flinching nociceptive behaviors were measured 0-60 min after formalin injection. Allodynia was measured at 3 and 6 h, and 1, 3, 5 and 7 days post-injection using the mechanical paw withdrawal threshold. Animals in the experimental group were given i.p. injections of CB1 and CB2 receptor antagonists AM281 and AM630 at a dose of 1 mg/kg concomitant with formalin, and then twice daily for the following 7 days. AM281 and AM630 enhanced nociceptive behaviors, and attenuated the bilateral mechanical paw withdrawal threshold, compared with the vehicle. The results indicate that CB1 and CB2 receptors mediate a tonically inhibitory action on formalin-induced inflammatory pain, especially long-term allodynia, in bilateral hind paws.

Bergenin Plays an Anti-Inflammatory Role via the Modulation of MAPK and NF-κB Signaling Pathways in a Mouse Model of LPS-Induced Mastitis.

Mastitis is a major disease in humans and other animals and is characterized by mammary gland inflammation. It is a major disease of the dairy industry. Bergenin is an active constituent of the plants of genus Bergenia. Research indicates that bergenin has multiple biological activities, including anti-inflammatory and immunomodulatory properties. The objective of this study was to evaluate the protective effects and mechanism of bergenin on the mammary glands during lipopolysaccharide (LPS)-induced mastitis. In this study, mice were treated with LPS to induce mammary gland mastitis as a model for the disease. Bergenin treatment was initiated after LPS stimulation for 24 h. The results indicated that bergenin attenuated inflammatory cell infiltration and decreased the concentration of NO, TNF-α, IL-1ß, and IL-6, which were increased in LPS-induced mouse mastitis. Furthermore, bergenin downregulated the phosphorylation of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPK) signaling pathway proteins in mammary glands with mastitis. In conclusion, bergenin reduced the expression of NO, TNF-α, IL-1ß, and IL-6 proinflammatory cytokines by inhibiting the activation of the NF-κB and MAPKs signaling pathways, and it may represent a novel treatment strategy for mastitis.

Association of folate deficiency and selected tumor marker concentrations in long-term hexavalent chromium exposed population.

Both hexavalent chromium [Cr (VI)] exposure and folate deficiency have been associated with increased cancer risks. Our previous studies have found folate deficiency in Cr (VI) exposed population. Here the relationship between some tumor markers and folate status in long-term Cr (VI) exposure was investigated carefully to show the multiple aspects of Cr (VI) carcinogenesis. A group of 115 workers occupationally exposed to chromate and 60 matched, unexposed controls in Shandong province of China were recruited. Environmental and biological exposure assessments including personal exposure to airborne Cr and Cr contents in erythrocytes were performed. Serum folate, plasma total homocysteine (tHcy) and plasma carcinoembryonic antigen (CEA), neuron specific enolase (NSE), squamous cell carcinoma antigen (SCC), cytokeratin fragment antigen 21-1 (CYFRA 21-1), cancer antigen 72-4 (CA72-4), as well as α-fetoprotein (AFP) were measured. Smoking index (SI) was also calculated to discriminate possible confounding effects of smoking status. Serum folate level decreased significantly, while plasma tHcy, CEA, NSE, SCC, CYFRA21-1, CA72-4 and AFP concentrations increased significantly after Cr (VI) exposure. Meanwhile, plasma CEA, NSE and SCC were negatively correlated with serum folate. SI was negatively correlated with serum folate but positively correlated with plasma tHcy, CEA and NSE levels. Present study suggests that folate deficiency was associated with increased cancer risks and might be affected by smoking in Cr (VI) exposed population. Folate might play a key role in Cr (VI) carcinogenesis although further detailed investigations are needed to clarify the mechanism of this process.