A bidirectional switch in the Shank3 phosphorylation state biases synapses toward up- or downscaling.

Homeostatic synaptic plasticity requires widespread remodeling of synaptic signaling and scaffolding networks, but the role of post-translational modifications in this process has not been systematically studied. Using deep-scale quantitative analysis of the phosphoproteome in mouse neocortical neurons, we found widespread and temporally complex changes during synaptic scaling up and down. We observed 424 bidirectionally modulated phosphosites that were strongly enriched for synapse-associated proteins, including S1539 in the autism spectrum disorder-associated synaptic scaffold protein Shank3.

Strong Aversive Conditioning Triggers a Long-Lasting Generalized Aversion.

Generalization is an adaptive mnemonic process in which an animal can leverage past learning experiences to navigate future scenarios, but overgeneralization is a hallmark feature of anxiety disorders. Therefore, understanding the synaptic plasticity mechanisms that govern memory generalization and its persistence is an important goal. Here, we demonstrate that strong CTA conditioning results in a long-lasting generalized aversion that persists for at least 2 weeks.

Homeostatic synaptic scaling establishes the specificity of an associative memory.

Correlation-based (Hebbian) forms of synaptic plasticity are crucial for the initial encoding of associative memories but likely insufficient to enable the stable storage of multiple specific memories within neural circuits. Theoretical studies have suggested that homeostatic synaptic normalization rules provide an essential countervailing force that can stabilize and expand memory storage capacity. Although such homeostatic mechanisms have been identified and studied for decades, experimental evidence that they play an important role in associative memory is lacking.

Efficacy and safety of combined directly acting antivirals for treatment of Chinese chronic hepatitis C patients in a real-world setting.

Aim: To assess the efficacy and safety of combined directly acting antivirals (DAAs) for the treatment of Chinese chronic hepatitis C (CHC) patients in a real-world setting.

Methods: Hospitalized CHC patients who were treated with DAAs at Peking University First Hospital between January 2015 and December 2016 were enrolled. Samples and clinical data were collected at 0 wk, 2 wk, 4 wk, 8 wk, 12 wk, or 24 wk during DAAs treatment and at 4 wk, 12 wk, and 24 wk after the end of treatment.

A Drosophila model of ALS reveals a partial loss of function of causative human PFN1 mutants.

Mutations in the profilin 1 (PFN1) gene are causative for familial amyotrophic lateral sclerosis (fALS). However, it is still not fully understood how these mutations lead to neurodegeneration. To address this question, we generated a novel Drosophila model expressing human wild-type and ALS-causative PFN1 mutants.

[The difference of IL-28B polymorphisms between hepatitis C patients with and without cryoglobulinemia].

Objective: To determine whether patients infected with chronic hepatitis C (CHC) show a differential distribution profile of IL-28B polymorphisms according to the presence of concomitant cryoglobulinemia.

Methods: Sixty-two consecutive CHC patients were enrolled in the study between December 2008 and December 2010. All patients received combination therapy of pegylated interferon alpha-2a (weekly, 180 g, subcutaneous injection) plus ribavirin (daily, 10to15 mg/kg body weight, oral) for 48 weeks, with individualized dosage adjustments according to the patient's clinical situation.

Cryoglobulinemia is an independent factor negatively associated with sustained virological response in chronic hepatitis C patients.

Background: Mixed cryoglobulinemia (MC) is one of the most common and severe symptoms in chronic hepatitis C patients. The aim of this study was to investigate whether mixed cryoglobulinemia is a factor associated with sustained virological response in chronic hepatitis C patients treated with combination therapy of pegylated interferon alpha-2a and ribavirin.

Methods: This is a single-center study including 57 chronic hepatitis C patients who received combination treatments of pegylated interferon alfa-2a and ribavirin.

Efficacy of pegylated interferon-alpha-2a plus ribavirin for patients aged at least 60 years with chronic hepatitis C.

Background: In China, patients with hepatitis C virus (HCV)-associated liver disease are getting older, and thus the number of deaths due to such disease is increasing. The efficacy of combination therapy with ribavirin and interferon for chronic HCV infection in elderly patients has not been fully clarified. The aim of the present study was to evaluate the efficacy and tolerability of the combination therapy in the elderly patients.

Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative disorder resulting from motor neuron death. Approximately 10% of cases are familial (FALS), typically with a dominant inheritance mode. Despite numerous advances in recent years, nearly 50% of FALS cases have unknown genetic aetiology.

[The effect of cryoglobulinemia on the antiviral therapy in patients with chronic hepatitis C].

Objective: To investigate the possible influence of cryoglobulinemia on the antiviral effect in chronic hepatitis C patients, who were treated with combination therapy of pegylated interferon alpha-2a and ribavirin.

Methods: Forty consecutive patients with chronic hepatitis C (CHC) were enrolled in the study. They received pegylated interferon alfa-2a (40kD, 180mug/w) along with ribavirin.

Prevalence of abnormal glycometabolism in patients with chronic hepatitis C and related risk factors in China.

Background: An epidemiologic link between hepatitis C virus (HCV) and abnormal glycometabolism had been established. This study was designed to investigate the prevalence of type 2 diabetes mellitus and insulin resistance, and to explore the relation between insulin resistance and hepatitis C virus genotype, serum hepatitis C virus-RNA level in chronic hepatitis C (CHC) patients.

Methods: Three hundred and fifty-nine consecutive patients (CHC, n = 296; chronic hepatitis B (CHB), n = 63) were evaluated.

Expressions of SE-1, CD31 and CD105 in the vascular endothelial cells and serum of rat with hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide. In order to investigate the molecular biologic mechanism of HCC's development, we studied the expressions of SE-1, CD105 and CD31 in tumor endothelial cells (TECs) of HCC and in the serum of rats.

Methods: We analyzed the expressions of SE-1, CD31 and CD105 in rat HCC tumor tissues using immunohistochemistry (IHC).

[Clinical features and prognosis of decompensated hepatitis C virus related cirrhosis].

Objective: To study the clinical features and prognosis of hepatitis C virus (HCV)-related cirrhosis after the first occurrence of complications.

Methods: The clinical data of 89 decompensated HCV-related cirrhosis patients were analyzed. Univariate and multivariate analyses of the factors influencing the clinical decompensation were conducted.

[An analysis of clinical characteristics and risk factors of cirrhosis-related hepatocellular carcinomas in patients with hepatitis C virus infection].

Objective: To study the epidemiological and clinical characteristics and risk factors of cirrhosis-related hepatocellular carcinomas (HCC) in patients with hepatitis C virus (HCV) infection.

Methods: Eighty-nine compensated and decompensated HCV cirrhosis patients were analyzed and followed-up. The main clinical and laboratory variables were analyzed as incidence factors of HCC with univariate analysis and multivariate analysis regression models.

[The histopathologic and clinical analysis of viral chronic hepatitis patients with negative serological viral markers].

Objective: To analyze the histopathological and clinical features of viral chronic hepatitis patients with negative serological viral markers.

Methods: 62 hepatitis patients with negative serological markers were assayed with serological viral hepatitis markers, liver function test and liver biopsies were enrolled in the study. Serum HBV DNA of HBV cases was analyzed by PCR.

[An analysis of the pathohistology of liver tissues, clinical features and prognostic factors of chronic hepatitis B virus carriers].

Objective: To study the correlations between clinical features and liver pathohistological changes of chronic hepatitis B virus (HBV) carriers and to discuss the factors which may influence the prognosis.

Methods: Ninety HBV carriers who had liver biopsies were enrolled in this study.

Results: (1) The mean follow-up period of the patients was 118 weeks.

[Serum autoantibodies of patients with chronic hepatitis C and the significance thereof in infection of hepatitis C virus].

Objective: To investigate the serum autoantibodies in patients with chronic hepatitis C and to investigate the significance of autoimmune reaction in hepatitis C virus (HCV) infected patients.

Methods: Peripheral blood samples were collected from 69 patients with chronic hepatitis C, 69 patients with chronic hepatitis B (HB), and 69 patients with autoimmune hepatitis (AIH). Indirect immunofluorescence technique was used to detect the serum anti nuclear antibody (ANA), anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (anti-SMA), and anti-liver-kidney antibody (anti-LKM).

Microwave-assisted enzyme-catalyzed reactions in various solvent systems.

The work describes the accelerated enzymatic digestion of several proteins in various solvent systems under microwave irradiation. The tryptic fragments of the proteins were analyzed by matrix-assisted laser desorption/ionization mass spectrometry. Under the influence of rapid microwave heating, these enzymatic reactions can proceed in a solvent such as chloroform, which, under traditional digestion conditions, renders the enzyme inactive.

[Clinical and pathological analysis of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome].

Objective: To explore clinical and histopathological characteristics of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome.

Methods: Clinical data and pathological findings of 10 patients were reviewed.

Results: Serum glutamine transpeptidase,alkaline phosphatase levels,alanine transaminase, aspartate transaminase, serum IgG and IgM were elevated in all the patients.