Deubiquitinase CYLD regulates excitatory synaptic transmission and short-term plasticity in the hippocampus.

The fate of proteins is determined by the addition of various forms of polyubiquitin during ubiquitin-mediated proteasomal degradation. Cylindromatosis (CYLD), a K63-specific deubiquitinase, is enriched in postsynaptic density fractions of the rodent central nervous system (CNS), but the synaptic role of CYLD in the CNS is poorly understand. Here we show that CYLD deficiency (Cyld-/-) results in reduced intrinsic hippocampal neuronal firing, a decrease in the frequency of spontaneous excitatory postsynaptic currents and a decrease in the amplitude of field excitatory postsynaptic potentials. Moreover, Cyld-/- hippocampus shows downregulated levels of presynaptic vesicular glutamate transporter 1 (vGlut1) and upregulated levels of postsynaptic GluA1, a subunit of the AMPA receptor, together with an altered paired-pulse ratio (PPR). We also found increased activation of astrocytes and microglia in the hippocampus of Cyld-/- mice. The present study suggests a critical role for CYLD in mediating hippocampal neuronal and synaptic activity.

Gitelman syndrome: A case report.

BACKGROUND: Gitelman syndrome (GS) is an autosomal recessive salt-losing renal tubulopathy arising from mutations in the thiazide-sensitive Na-Cl cotransporter gene. Due to its low incidence and lack of awareness, GS can be easily misdiagnosed or missed in diagnosis. CASE SUMMARY: A 24-year-old male presented with > 4 years of repeated limb weakness without any treatment. The previous day, the patient was bitten by ants and showed weakness of the lower limbs. The patient had hypokalemia (1.66-2.83 mmol/L), hypomagnesemia (0.4 mmol/L), hypocalciuria (1.51-2.46 mmol/d), metabolic alkalosis (7.47-7.54), normal blood pressure, and increased activity of aldosterone and plasma renin activity (PRA) (PRA 6.4 and 16.45 ng/mL/h and aldosterone 330.64 and 756.82 pg/mL in the supine and upright position, respectively). In addition, SLCI2A3 gene mutation with GS was diagnosed. Oral and intravenous supplementation with potassium and magnesium was initiated. Serum magnesium returned to 0.48 mmol/L and serum potassium returned to 3.08 mmol/L, alleviating the patient's fatigue symptoms. CONCLUSION: GS should be considered in patients with hypokalemia complicated with hypomagnesemia. Genetic testing is essential to confirm the diagnosis.

Ancient Chinese Herbal Recipe Huanglian Jie Du Decoction for Ischemic Stroke: An Overview of Current Evidence.

Ischemic stroke is a major cause of mortality and neurological morbidity worldwide. The underlying pathophysiology of ischemic stroke is highly complicated and correlates with various pathological processes, including neuroinflammation, oxidative stress injury, altered cell apoptosis and autophagy, excitotoxicity, and acidosis. The current treatment for ischemic stroke is limited to thrombolytic therapy such as recombinant tissue plasminogen activator. However, tissue plasminogen activator is limited by a very narrow therapeutic time window (<4.5 hours), selective efficacy, and hemorrhagic complication. Hence, the development of novel therapies to prevent ischemic damage to the brain is urgent. Chinese herbal medicine has a long history in treating stroke and its sequela. In the past decades, extensive studies have focused on the neuroprotective effects of Huanglian Jie Du decoction (HLJDD), an ancient and classical Chinese herbal formula that can treat a wide spectrum of disorders including ischemic stroke. In this review, the current evidence of HLJDD and its bioactive components for ischemic stroke is comprehensively reviewed, and their potential application directions in ischemic stroke management are discussed.

[Risk factors of intra-abdominal infection following gastrectomy in gastric cancer patients].

OBJECTIVE: To investigate the main risk factors associated with intra-abdominal infection(IAI) following gastrectomy in gastric cancer patients. METHODS: Case-control study was used to investigate the clinical data of 1728 gastric carcinoma cases retrospectively by Logistic regressive analysis. RESULTS: Univariate Logistic regressive analysis showed 16 factors, including age, malnutrition, chronic obstructive pulmonary disease(COPD), diabetes mellitus(DM), heart diseases, prothrombin time, lymphocyte count, tumor size, ascites, invasion to the adjacent organ, neoplasm TNM staging (UICC, 1997), methods of gastrectomy, blood loss, operative time, blood transfusion and extent of lymph nodal dissection,were associated with postoperative intra-abdominal infection. Binary Logistic regression analysis found that extent of lymph nodal dissection(N(2)(+) approximately N(3) and N(2)), invasion to the adjacent organ, DM, operative time, age and lymphocyte count were the independent risk factors associated with mortality. CONCLUSION: Necessary interventions should be carried out to prevent IAI referring to above risk factors.