Plasticity of neuronal excitability and synaptic balance in the anterior nucleus of paraventricular thalamus after nerve injury.

The anterior nucleus of the paraventricular thalamus (aPVT) integrates various synaptic inputs and conveys information to the downstream brain regions for arousal and pain regulation. Recent studies have indicated that the PVT plays a crucial role in the regulation of chronic pain, but the plasticity mechanism of neuronal excitability and synaptic inputs for aPVT neurons in neuropathic pain remains unclear. Here, we report that spinal nerve ligation (SNL) significantly increased the neuronal excitability and reset the excitatory/inhibitory (E/I) synaptic inputs ratio of aPVT neurons in mice. SNL significantly increased the membrane input resistance, firing frequency, and the half-width of action potential. Additionally, SNL enlarged the area of afterdepolarization and prolonged the rebound low-threshold spike following a hyperpolarized current injection. Further results indicate that an inwardly rectifying current density was decreased in SNL animals. SNL also decreased the amplitude, but not the frequency of spontaneous excitatory postsynaptic currents (sEPSCs), nor the amplitude or frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) of aPVT neurons. Moreover, SNL disrupted the E/I synaptic ratio, caused a decrease in weighted tau and half-width of averaged sIPSCs, but did not change these physiological properties of averaged sEPSCs. Finally, pharmacological activation of the GABAA receptor at aPVT could effective relieve SNL-induced mechanical allodynia in mice. These results reveal the plasticity of intrinsic neuronal excitability and E/I synaptic balance in the aPVT neurons after nerve injury and it may play an important role in the development of pain sensitization.

An Analysis of the Pathogenic Genes and Mutation Sites of Macrodactyly.

OBJECTIVE: This study aimed to explore the pathogenic genes and mutation sites of macrodactyly. METHODS: Whole-exome sequencing was performed on the pathological tissue and peripheral blood of 12 patients with macrodactyly who were operated in our hospital between June 2018 and May 2020. In order to conduct comprehensive bioinformatics analysis and screen the pathogenic genes of macrodactyly, the patients were divided into four groups: macrodactyly of finger group, macrodactyly of foot group, macrodactyly and syndactyly of finger group, and macrodactyly and syndactyly of foot group. The results of the whole-exome sequencing were verified using Sanger sequencing in order to clarify the pathogenic genes and mutation sites of macrodactyly, and immunohistochemical analysis of the protein signaling pathways encoded by the pathogenic genes was performed to observe the protein expression and further verify the mutant genes. RESULTS: In the comprehensive bioinformatics analysis and Sanger verification of the whole-exome sequencing, the PIK3CA gene mutation was screened as the pathogenic gene of macrodactyly. The mutation sites were identified as the p.E542K (c.G1624A) and p.E545K (c.G1633A) sites of exon10 and the p.H1047R (c.A3140G) and p.G1049R (c.G3145C) sites of exon21. Among these, the p.G1049R (c.G3145C) locus was found in macrodactyly for the first time. The mutation of the PIK3CA gene was also found to lead to increased expression of serine-threonine kinase (AKT) in adipocytes in the PI3K-AKT-mTOR signaling pathway. CONCLUSION: Mutation of the PIK3CA gene leads to the enhancement of the PI3K-AKT-mTOR signaling pathway, which is the cause of macrodactyly. There is also some diversity in PIK3CA gene mutation sites.

The patterns of distant metastasis and prognostic factors in patients with primary metastatic Ewing sarcoma of the bone.

BACKGROUND: Ewing sarcoma (ES) of bone is accounting for the second most common type of primary bone cancer in children and adolescents. However, the patterns of distant metastasis (DM) and the effect of the sites of DM on survival outcomes were not investigated. AIMS: This study aimed to investigate the patterns of DM and the prognostic factors related to outcomes in primary metastatic ES of the bone. METHODS: Patients who were diagnosed with primary metastatic ES between 2010 and 2018 were identified from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier analysis, log-rank tests, and Cox proportional-hazards regression models were used for statistical analyses. RESULTS: We identified 277 patients in this study and 95.3% of them (n = 264) receiving chemotherapy. A total of 371 sites of DM were observed. Lung was the most common distant metastatic site (n = 182, 49.1%), followed by bone (n = 139, 37.5%), distant lymph node (n = 26, 7.0%), liver (n = 14, 3.8%), and brain (n = 10, 2.7%). Three-year cause-specific survival (CSS) was 56.1% in the entire cohort. Older age (hazard ratio [HR] 2.210, P < 0.001) and bone metastasis (HR 1.903, P = 0.002) were the independent prognostic factors associated with inferior CSS. Similar results were found in those with bone-only metastasis (n = 80) or lung-only metastasis (n = 117), which showed that patients with bone-only metastasis had an inferior CSS compared to those with metastases only to the lung (HR 1.926, P = 0.005). CONCLUSIONS: Lung and bone are the most frequently distant metastatic sites in patients with primary metastatic ES of bone. Bone metastasis is an independent risk factor for inferior survival.

Magnolol, a natural aldehyde dehydrogenase-2 agonist, inhibits the proliferation and collagen synthesis of cardiac fibroblasts.

Inhibiting myocardial fibrosis can help prevent cardiovascular diseases, including heart failure. Magnolol (Mag), a natural component of Magnoliae officinalis, has been reported to inhibit fibrosis. However, the mechanism of Mag activity and its effects on myocardial fibrosis remain unclear. Here, we investigated the involvement of ALDH2, an endogenous protective agent against myocardial fibrosis, in the Mag-mediated inhibition of cardiac fibroblast proliferation and collagen synthesis. We found that Mag significantly inhibited cardiac fibroblast proliferation and collagen synthesis, based on the results of MTT, EdU and western blot assays. Moreover, molecular docking, molecular dynamics simulation and surface plasmon resonance (SPR) assays showed that Mag could bind directly and stably to ALDH2. Further analysis of the mechanism of these effects indicated that treatment with Mag dose-dependently enhanced ALDH2 activity without altering protein expression. Mag could enhance the activity of recombinant human ALDH2 proteins with a half-maximal effective concentration of 5.79 × 10-5 M. In addition, ALDH2 activation via Alda-1 inhibited cardiac fibroblast proliferation and collagen synthesis, while ALDH2 inhibition via daidzin partially blocked the suppressive effects of Mag. In summary, Mag may act as a natural ALDH2 agonist and inhibit cardiac fibroblast proliferation and collagen synthesis.

The role of ginsenoside Rb1, a potential natural glutathione reductase agonist, in preventing oxidative stress-induced apoptosis of H9C2 cells.

BACKGROUND: Oxidative stress-induced cardiomyocytes apoptosis is a key pathological process in ischemic heart disease. Glutathione reductase (GR) reduces glutathione disulfide to glutathione (GSH) to alleviate oxidative stress. Ginsenoside Rb1 (GRb1) prevents the apoptosis of cardiomyocytes; however, the role of GR in this process is unclear. Therefore, the effects of GRb1 on GR were investigated in this study. METHODS: The antiapoptotic effects of GRb1 were evaluated in H9C2 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, annexin V/propidium iodide staining, and Western blotting. The antioxidative effects were measured by a reactive oxygen species assay, and GSH levels and GR activity were examined in the presence and absence of the GR inhibitor 1,3-bis-(2-chloroethyl)-1-nitrosourea. Molecular docking and molecular dynamics simulations were used to investigate the binding of GRb1 to GR. The direct influence of GRb1 on GR was confirmed by recombinant human GR protein. RESULTS: GRb1 pretreatment caused dose-dependent inhibition of tert-butyl hydroperoxide-induced cell apoptosis, at a level comparable to that of the positive control N-acetyl-L-cysteine. The binding energy between GRb1 and GR was positive (-6.426 kcal/mol), and the binding was stable. GRb1 significantly reduced reactive oxygen species production and increased GSH level and GR activity without altering GR protein expression in H9C2 cells. Moreover, GRb1 enhanced the recombinant human GR protein activity in vitro, with a half-maximal effective concentration of ≈2.317 µM. Conversely, 1,3-bis-(2-chloroethyl)-1-nitrosourea co-treatment significantly abolished the GRb1's apoptotic and antioxidative effects of GRb1 in H9C2 cells. CONCLUSION: GRb1 is a potential natural GR agonist that protects against oxidative stress-induced apoptosis of H9C2 cells.

The anxiolytic-like effects of ginsenoside Rg2 on an animal model of PTSD.

Post traumatic stress disorder (PTSD) is one of the mental illness. The antidepressant-like properties of ginsenoside Rg2 (GRg2) have been shown, while little is known about its anti-PTSD-like effects. In the present study, the PTSD-associated behavioral deficits in rats were induced following exposure to single prolonged stress (SPS). The results showed that the decreased time and entries in the open arms in elevated plus maze test (EPMT) and increased freezing duration in contextual fear paradigm (CFP) were reversed by GRg2 (10 and 20 mg/kg) without affecting the locomotor activity. In addition, GRg2 (10 and 20 mg/kg) could block the decreased levels of progesterone, allopregnanolone, serotonin (5-HT), 5-Hydroxyindoleacetic acid (5-HIAA), corticotropin releasing hormone (CRH), corticosterone (Cort) and adrenocorticotropic hormone (ACTH) in the brain or serum. In summary, GRg2 alleviated the PTSD-associated behavioral deficits with biosynthesis of neurosteroids, normalization of serotonergic system and HPA axis dysfunction.

3,5-Dicaffeoylquinic acid protects H9C2 cells against oxidative stress-induced apoptosis via activation of the PI3K/Akt signaling pathway.

BACKGROUND: Oxidative stress-induced apoptosis plays an important role in the development of heart failure. 3,5-Dicaffeoylquinic acid (3,5-diCQA), a phenolic compound, has shown protective effects against oxidative stress in many diseases. OBJECTIVE: The objective of this study was to investigate the anti-apoptosis potential of 3,5-diCQA in cardiomyocyte cells under oxidative stress and explore its underlying mechanisms. DESIGN: A model of tert-butyl hydroperoxide (TBHP)-induced apoptosis in a cardiomyocyte cell line (H9C2) was established. Cell viabilities on cell lines were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay. The apoptosis was measured by hoechst33342 and propidium iodide (PI) fluorescent staining. PI (in red) stained the regions of cell apoptosis; Hoechet33342 (in blue) stained the nuclei. The Western blot was used to determine the expressions of related proteins such as p-PI3K: phosphorylated phosphatidylinositol-3-kinase (p-PI3K), phosphorylated Serine and Threonine kinase AKT (p-AKT), p-PTEN, Bcl-2, Bax, and caspase-3. Afterward, a PI3K inhibitor, LY294002, was applied to confirm the influence of the PI3K/Akt pathway on TBHP-treated cells of 3,5-diCQA. Then, H9C2 cells were pre-incubated with 3,5-diCQA alone to determine if the expression of activated PI3K/Akt signaling was mediated by 3,5-diCQA in H9C2 cells. RESULTS: The results showed that TBHP resulted in an increase in cardiomyocyte apoptosis, whereas 3,5-diCQA treatment protected cells from TBHP-induced apoptosis in a dose-dependent manner. Moreover, 3,5-diCQA decreased expressions of Bax and caspase-3 but increased the phosphorylation levels of PI3K and Akt in TBHP-treated cells, which are the key molecules mediating cell survival, whereas phosphatase and tensin homologue deleted on chromosome 10 (PTEN) phosphorylation was unchanged. Importantly, pre-incubation with a PI3K inhibitor (LY294002) partly abolished the anti-apoptosis effects of 3,5-diCQA. Further, 3,5-diCQA enhanced the phosphorylation levels of PI3K and Akt in H9C2 cells directly, while LY294002 attenuated the effects of 3,5-diCQA on PI3K and Akt. CONCLUSION: This study suggested that 3,5-diCQA rescued myocardium from apoptosis by increasing the activation of the PI3K/Akt signaling pathway.

Luteolin Inhibits Vascular Smooth Muscle Cell Proliferation and Migration by Inhibiting TGFBR1 Signaling.

Vascular smooth muscle cell (VSMC) proliferation and migration play a critical role in the development of arterial remodeling during various vascular diseases including atherosclerosis, hypertension, and related diseases. Luteolin is a food-derived flavonoid that exerts protective effects on cardiovascular diseases. Here, we investigated whether transforming growth factor-ß receptor 1 (TGFBR1) signaling underlies the inhibitory effects of luteolin on VSMC proliferation and migration. We found that luteolin reduced the proliferation and migration of VSMCs, specifically A7r5 and HASMC cells, in a dose-dependent manner, based on MTS and EdU, and Transwell and wound healing assays, respectively. We also demonstrated that it inhibited the expression of proliferation-related proteins including PCNA and Cyclin D1, as well as the migration-related proteins MMP2 and MMP9, in a dose-dependent manner by western blotting. In addition, luteolin dose-dependently inhibited the phosphorylation of TGFBR1, Smad2, and Smad3. Notably, adenovirus-mediated overexpression of TGFBR1 enhanced TGFBR1, Smad2, and Smad3 activation in VSMCs and partially blocked the inhibitory effect of luteolin on TGFBR1, Smad2, and Smad3. Moreover, overexpression of TGFBR1 rescued the inhibitory effects of luteolin on the proliferation and migration of VSMCs. Additionally, molecular docking showed that this compound could dock onto an agonist binding site of TGFBR1, and that the binding energy between luteolin and TGFBR1 was -10.194 kcal/mol. Simulations of molecular dynamics showed that TGFBR1-luteolin binding was stable. Collectively, these data demonstrated that luteolin might inhibit VSMC proliferation and migration by suppressing TGFBR1 signaling.

Anti-inflammatory and immune response regulation of Si-Ni-San in 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Si-Ni-San (SNS) is a well-known decoction in traditional Chinese medicine. Although studies have indicated that the anti-inflammatory and anti-allergic properties of SNS and its components can account for their therapeutic effects, the role and mechanism of SNS in treating skin dysfunction remain unclear. AIM OF THE STUDY: Atopic dermatitis (AD), a disorder known for its prevalence in infants and adults, severely influences the quality of life of affected patients. In this study, we aimed to investigate the anti-inflammatory and immune response modulations of SNS in 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin dysfunction. MATERIALS AND METHODS: Dermatitis was induced in Kunming mice by the topical application of DNCB. SNS or dexamethasone (positive control) was topically applied every day over the course of the 21-day study. The following were assessed: dermatitis severity scores; ear and dorsal skin haematoxylin and eosin staining; interleukin (IL)- 1α, IL-1ß, IL-2, IL-4, IL-6, and tumour necrosis factor (TNF)-α cytokine levels in the serum; spleen index; spleen CD4 + /CD8 + T lymphocyte ratio; and phosphorylation levels of mitogen-activated protein kinases (MAPKs- p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK)), IκB-α, and nuclear factor (NF)-κB (p65) in skin lesions. RESULTS: SNS significantly alleviated the symptoms of AD-like lesions induced by DNCB, decreased the infiltration of inflammatory cells in the ear and dorsal tissues, suppressed the increased cytokine levels in the serum, reduced the CD4 + /CD8 +T lymphocyte ratio in the spleen, and downregulated the activation of MAPKs, IκB-α, and NF-κB (p65) in the dorsal skin. The effects were similar to those of dexamethasone. CONCLUSIONS: SNS alleviated the DNCB-induced AD-like skin dysfunction in mice through anti-inflammatory and immune system modulation, indicating that SNS shows potential for AD treatment in clinical settings.

Comparison of the effects of local treatment strategies in non-metastatic Ewing sarcoma of bone.

BACKGROUND: To investigate the optimal local treatment strategies for patients with non-metastatic Ewing sarcoma (ES) of bone. METHODS: Patients with ES of bone were identified using the Surveillance Epidemiology and End Results database. Kaplan-Meier log-rank test and Cox regression models were performed to assess the effect of the types of local treatment strategies on cause-specific survival and overall survival. RESULTS: 560 patients were included with a median age of 16 years. A total of 284, 162 and 114 patients received surgery alone, surgery and radiotherapy, and radiotherapy alone, respectively. The types of local treatment strategies had no effect on survival outcomes in multivariate analysis. In the subgroup analysis of patients with tumor diameter <8 cm, surgery ± radiotherapy had a significantly improved cause-specific survival (P = 0.039), and had potential to improve overall survival (P = 0.070) in multivariate analysis. The local treatment strategies had no effect on survival in patients with different tumor location. CONCLUSION: There is no local treatment of choice for non-metastatic ES of bone in terms of survival. More well-designed studies are needed to confirm our findings and investigate the role of various local treatment strategies in relation to primary tumor diameter.

Therapeutic effect of oridonin on mice with prostate cancer.

OBJECTIVE: To investigate the therapeutic effect and the related mechanism of oridonin on mice with prostate cancer. METHODS: Sixty BALB/C male nude mice were selected. A model of RM-1 cell transplantation tumor of prostate cancer was built by the subcutaneous inoculation of RM-1 cells. After that, those 60 experimental mice were randomly divided into groups A, B and C. Each group had 20 mice. Mice in group A were treated with 0.2 mL of normal saline (0.9%) by intraperitoneal injection once a day; mice in group B received intraperitoneal injection of 1.875 mg/mL of oridonin once a day; and mice in group C received intraperitoneal injection of 7.5 mg/mL of oridonin once a day. Mice in the three groups were treated uninterruptedly for 5 weeks and were all killed. Then, tumors were excised and weighed to calculate their growth inhibitory rate, volume increment and anti-tumor rate. Thymus and spleen of mice in the three groups were collected to calculate the thymus and spleen index. Immunohistochemical staining was applied to observe the expression of caspase-3 in prostate cancer tissue of mice of the three groups. RESULTS: The qualities and volume increment of tumors in groups B and C were significantly lower than those of group A (P < 0.05); the qualities and volume increment of tumors in groups C were evidently lower than those of group B (P < 0.05); the tumor volume increment and anti-tumor rate in group C were obviously higher than those of group B (P < 0.05); the thymus and spleen indexes of groups B and C were distinctly higher than those of group A (P < 0.05); comparison of the thymus and spleen indexes between group B and group C showed no statistical differences (P > 0.05). Immumohistochemical staining revealed that the caspase-3 protein in prostate cancer tissue of mice of group A expressed negatively with colorless or light-colored karyon; while the caspase-3 protein in prostate cancer tissue of mice of group B expressed positively with dark-colored karyon, centralized distribution and granular sensation; and the caspase-3 in prostate cancer tissue of mice of group C showed strong positive expression with big and darker colored karyon and dense distribution. CONCLUSIONS: Oridonin can inhibit the growth of RM-1 prostate cancer cells effectively and have great therapeutic effects on RM-1 cell transplantation tumor of prostate cancer.

Clinical significance of FABP2 expression in newborns with necrotizing enterocolitis.

BACKGROUND: This meta-analysis aimed to determine the role of human fatty acid binding protein 2 (FABP2) expression in the diagnosis of necrotizing enterocolitis (NEC) of newborns. DATA SOURCES: Eligible studies for further statistical analysis were identified from various databases including PubMed, Expert Medica Database, Web of Science, Cochrane Library, Google Scholar, China BioMedicine and China National Knowledge Infrastructure. Random effects model was used, and summary standardized mean difference (SMD) with its 95% confidence interval (CI) was calculated to assess the association of FABP2 expression and NEC. RESULTS: Ten articles which included 572 infants (262 infants with NEC and 310 healthy controls) were included in the current meta-analysis. FABP2 showed a positive relationship with NEC of newborns (SMD=2.88, 95% CI=2.09-3.67, P<0.001). And FABP2 expression was higher in patients with advanced stage of NEC (stage III or stage II+III) than in those with early stage of NEC (stage I) (SMD=-0.48, 95% CI=-0.87 to -0.09, P=0.015). Ethnicity-stratified analysis yielded significantly different estimates with a high FABP2 expression in NEC in both Caucasians (SMD=3.16, 95% CI=1.90-4.43, P<0.001) and Asians (SMD=2.57, 95% CI=1.50-3.64, P<0.001). Sample-based subgroup analysis showed that FABP2 expression was positively correlated with neonatal NEC in both urinary- and blood-sample subgroups (all P<0.05). CONCLUSION: The results prove that the high FABP2 expression is related to the damage to intestinal cells, which may be a possible early detection marker identifying neonatal NEC.

Abundance and significance of neuroligin-1 and glutamate in Hirschsprung's disease.

AIM: To investigate the abundance and potential diagnostic significance of neuroligin-1 and glutamate (Glu) in Hirschsprung's disease (HSCR). METHODS: Ninety children with HSCR and 50 children without HSCR matched for similar nutritional status, age and basal metabolic index were studied. The expression and localization of neuroligin-1 and Glu were assessed using double-labeling immunofluorescence staining of longitudinal muscles with adherent myenteric plexus from the surgically excised colon of children with HSCR. Western blot analysis, quantitative real-time PCR (qRT-PCR) and immunohistochemistry were performed to evaluate the abundance of neuroligin-1 and Glu in different HSCR-affected segments (ganglionic, transitional, and aganglionic segments). Enzyme-linked immunosorbent assay (ELISA) was used to detect and compare serum Glu levels in the long-segment HSCR, short-segment HSCR and non-HSCR samples. RESULTS: Neuroligin-1 and Glu were co-expressed highest to lowest in the ganglionic, transitional and aganglionic segments based on Western blot (neuroligin-1: 0.177 ± 0.008 vs 0.101 ± 0.006, 0.177 ± 0.008 vs 0.035 ± 0.005, and 0.101 ± 0.006 vs 0.035 ± 0.005, P < 0.005; Glu: 0.198 ± 0.006 vs 0.115 ± 0.008, 0.198 ± 0.006 vs 0.040 ± 0.003, and 0.115 ± 0.008 vs 0.040 ± 0.003, P < 0.005) and qRT-PCR (neuroligin-1: 9.58 × 10(-5) ± 9.94 × 10(-6) vs 2.49 × 10(-5) ± 1.38 × 10(-6), 9.58 × 10(-5) ± 9.94 × 10(-6) vs 7.17 × 10(-6 ±) 1.12 × 10(-6), and 2.49 × 10(-5) ± 1.38 × 10(-6) vs 7.17 × 10(-6) ± 1.12 × 10(-6), P < 0.005). Serum Glu level was the highest to lowest in the non-HSCR, short-type HSCR and long-type HSCR samples based on ELISA (in nmol/µL, 0.93 ± 0.31 vs 0.57 ± 0.25, 0.93 ± 0.31 vs 0.23 ± 0.16, and 0.57 ± 0.25 vs 0.23 ± 0.16, P < 0.005). CONCLUSION: Neuroligin-1 and Glu may represent new markers of ganglion cells, whose expression may correlate with the pathogenesis, diagnosis, differential diagnosis or classification of HSCR.

Antioxidant effect of salvianolic acid B on hippocampal CA1 neurons in mice with cerebral ischemia and reperfusion injury.

OBJETIVE: To investigate the neuroprotective effects and underlying mechanisms of salvianolic acid B (Sal B) extracted from Salvia miltiorrhiza on hippocampal CA1 neurons in mice with cerebral ischemia reperfusion injury. METHODS: Forty male National Institute of Health (NIH) mice were randomly divided into 4 groups with 10 animals each, including the sham group, the model group, the SalB group (SalB 22.5 mg/kg) and the nimodipine (Nim) group (Nim 1 mg/kg). A mouse model of cerebral ischemia and reperfusion injury was established by bilateral carotid artery occlusion for 30 min followed by 24-h reperfusion. The malondialdehyde (MDA) content, the nitric oxide synthase (NOS) activity, the superoxide dismutase (SOD) activity and total antioxidant capability (T-AOC) of the pallium were determined by biochemistry methods. The morphologic changes and Bcl-2 and Bax protein expression in hippocampal CA1 neurons were observed by using hematoxylineosin staining and immunohistochemistry staining, respectively. RESULTS: In the SalB group, the MDA content and the NOS activity of the pallium in cerebral ischemia-reperfusion mice significantly decreased and the SOD activity and the T-AOC significantly increased, as compared with the model group (P<0.05 or P<0.01). The SalB treatment also rescued neuronal loss (P<0.01) in the hippocampal CA1 region, strongly promoted Bcl-2 protein expression (P<0.01) and inhibited Bax protein expression (P<0.05). CONCLUSIONS: SalB increases the level of antioxidant substances and decreases free radicals production. Moreover, it also improves Bcl-2 expression and reduces Bax expression. SalB may exert the neuroprotective effect through mitochondria-dependent pathway on hippocampal CA1 neurons in mice with cerebral ischemia and reperfusion injury and suggested that SalB represents a promising candidate for the prevention and treatment of ischemic cerebrovascular disease.

Administration of a novel penicillamine-bound membrane: a preventive and therapeutic treatment for abdominal adhesions.

BACKGROUND: Adhesions formation is a significant postsurgical complication. At present, there is no effective method for preventing adhesions formation 1, although barrier products such as Dextran (Dex) 2 and sodium hyaluronate (SH) 3 have proved the most clinically successful 456, This study is designed to investigate the preventive and therapeutic potential of a novel penicillamine-bound membrane for abdominal adhesions formation. METHODS: 150 rats were involved in the present study. All animals were randomly divided into 6 groups (1 vehicle group and 5 test groups respectively treated with dextran, sodium hyaluronate, penicillamine, penicillamine-bound membrane or non-penicillamine-bound membrane). The occurrence, grade and score of abdominal adhesions were compared between the different groups. The breaking strength of incision was compared between the vehicle group and the penicillamine, membrane with/without penicillamine - treated groups. Expression of collagen type I was compared between the vehicle and penicillamine-treated group. The occurrence of adhesions was compared between the Dextran (Dex), sodium hyaluronate (SH), penicillamine-treated group and membrane with or without penicillamine- treated groups. RESULTS: Penicillamine and penicillamine-bound membrane had significant preventive effects on abdominal adhesions formation, better than dextran, sodium hyaluronate and non-penicillamine-bound membrane. However, neither of them influenced incision healing, although they insignificantly decreased the breaking strength of the incision. Penicillamine-bound membrane, which can be loaded locally and more efficaciously, shows greater advantages than penicillamine. CONCLUSIONS: Penicillamine-bound membrane can be applied as an effective therapeutic intervention for abdominal adhesions with inconsequential side effects.

[Esophagogastrostomy by side-to-side anastomosis in prevention of anastomotic stricture: a randomized clinical trial].

OBJECTIVE: To compare a side-to-side esophagogastric anastomosis with conventional hand-sewn or stapled esophagogastrostomy for prevention of anastomotic stricture by randomized clinical trial. METHODS: Between November 2007 and September 2008, 160 patients with esophageal carcinoma or gastric cardia cancer were consecutively admitted and underwent surgical treatment. After excluding 5 patients (2 refused to participate in and 3 did not meet inclusion criteria), the remaining 155 patients were completely randomized to receive either a side-to-side esophagogastric anastomosis (SS group), or the conventional hand-sewn (HS group), or a circular stapled (CS group) anastomosis, after the removal of esophageal tumor. The primary outcome measured the incidence of anastomotic stricture at 3 months after the operation (defined as the diameter of the anastomotic orifice

Laparoscopic management of type I choledochal cyst in adults: cyst resection, assisted Roux-en-Y reconstruction and hepaticojejunostomy.

Due to improvement of instrumentation and surgeons' skills, the correction of congenital biliary tract anomalies has been performed by the laparoscopic approach. Because of the high rate of associated malignancy of the biliary system in middle-aged adults, treatment for choledochal cyst is necessary, especially in adult patients. We report on the laparoscopic excision and hepaticoduodenostomy of type I choledochal cysts in five adult patients. To facilitate the procedure, the creation of a Roux-en-Y reconstruction was performed with a minimal abdominal incision. All patients had an uneventful recovery with no major complications. Most were discharged on day 8 after the procedure. At a follow-up of two years, they were still asymptomatic, showing no cholangitis or anicteric. Laparoscopic management for choledochal cyst is an advantageous approach, so it is feasible and will probably become an accepted method in further clinical application.

The relationship between expressions of the laminin gene and RET gene in Hirschsprung's disease.

BACKGROUND: The cause of Hirschsprung's disease (HD) remains unclear, but currently there are two theories: the mutation of the RET gene and the change of enteric microenvironment. This study was undertaken to elucidate the cause of HD by assessing the expression of laminin (LN), laminin gene, and the RET gene in the aganglionic segment, transitional zone and normal segment of the colon in patients with HD. METHODS: Specimens of the aganglionic segment, transitional zone, and normal segment of the colon from 27 cases of HD were stained immunohistologically by a PV 9000 polymer detection system. Photos were taken by the RS image system, and the staining area of each image was calculated by a JD 801 image analysis system. The qualitative expressions of the laminin gene and RET gene of these three segments in the 27 cases were detected by reverse transcription-polymerase chain reaction (RT-PCR), and the difference of the expressions was shown by the alpha 9900 image analysis system. The quantitative expressions of the laminin gene and RET gene in the three segments were detected by real-time quantitative PCR, and the difference of the expression was shown by SDS software. RESULTS: The laminin and laminin gene were expressed in all the three segments. The expression was higher in the aganglionic segment than in the dilated segment, and the expression decreased stepwisely from the aganglionic segment to the normal segment, while the expression of the RET gene was opposite, showing an increased segmenting from the aganglionic segment to the normal segment. The correlation between the expressions of the two genes was negatively correlated. CONCLUSIONS: The highly increased expression of LN in the aganglionic segment may cause early differentiation, early maturation and premature ecesis of enteric nervous cells. The change of the microenvironment of colon wall may be the cause of HD. The negative correlation between the expression of the two genes may be closely related to the occurrence of HD.

[Study on the detection of positive selected codons on HA1 sequence of human influenza A subtype H3N2].

OBJECTIVE: To elucidate the evolution pattern of human influenza virus A H3 subtype by detecting positive selected codons in hemagglutinin gene. METHODS: All H3 sequences in NCBI GenBank and influenza sequence database were downloaded and two step cluster method was applied to divide sequences into six groups, which were corresponding to different period by turns. Fixed Effect Model was applied to detect positive selected codons in each group, and two step cluster method was then used again to summarize variation patterns of selective pressure among sites. RESULTS: Positive selected codons were different in groups corresponding different periods. 50 amino acid codons had been identified as positive selected sites in at least one time span. Among them, 42 codons belonged to one of the five known antigen-combinng regions. A larger amount of sites as well as relatively higher selection pressure were identified in antibody combining regions A and B. Results showed that the 50 sites could be divided into seven different patterns. While other six patterns corresponding to positive selected codons at only one time span, the sites of the seventh pattern were under positive selection in several periods. CONCLUSION: Positive selection codons in evolution of H3A1 strains were alternated in different time period whereas antibody combining regions A and B played more important roles in the evolution process. Other 8 identified codons out of the antibody combining regions might belong to unknown antigen regions.