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Major depressive disorder (MDD) is a common neuropsychiatric disorder affecting the mood and mental well-being. Its pathophysiology remains elusive due to the complexity and heterogeneity of this disorder that affects millions of individuals worldwide. Chronic stress is frequently cited as the one of the risk factors for MDD. To date, the conventional monoaminergic theory (serotonin, norepinephrine, and/or dopamine dysregulation) has received the most attention in the treatment of MDD, and all available classes of antidepressants target these monoaminergic systems. However, the contributions of other neurotransmitter systems in MDD have been widely reported. Emerging preclinical and clinical findings reveal that maladaptive glutamatergic neurotransmission might underlie the pathophysiology of MDD, thus revealing its critical role in the neurobiology of MDD and as the therapeutic target. Aiming beyond the monoaminergic hypothesis, studies of the neurobiological mechanisms underlying the stress-induced impairment of AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-glutamatergic neurotransmission in the brain could provide novel insights for the development of a new generation of antidepressants without the detrimental side effects. Here, the authors reviewed the recent literature focusing on the role of AMPA-glutamatergic neurotransmission in stress-induced maladaptive responses in emotional and mood-associated brain regions, including the hippocampus, amygdala, prefrontal cortex, nucleus accumbens and periaqueductal gray.

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Although hepatitis C virus (HCV) prevails in patients receiving methadone maintenance treatment (MMT), most do not receive anti-HCV therapy. This single-center observational study aimed to achieve HCV micro-elimination at an MMT center during the COVID-19 pandemic using a collaborative referral model, which comprised a referral-for-diagnosis stage (January 2020 to August 2020) and an on-site-diagnosis stage (September 2020 to January 2021). A multidisciplinary team was established and all MMT center patients were enrolled. HCV micro-elimination was defined as >90% of HCV-infected patients diagnosed and >80% of HCV-viremic patients treated. A total of 305 MMT patients, including 275 (90.2%) anti-HCV seropositive patients, were enrolled. Among 189 HCV-infected patients needing referral, the accumulative percentage receiving HCV RNA testing increased from 93 (49.2%) at referral-for-diagnosis stage to 168 (88.9%) at on-site-diagnosis stage. Among 138 HCV-viremic patients, the accumulative percentage receiving direct-acting antiviral (DAA) therapy increased from 77 (55.8%) at referral-for-diagnosis stage to 129 (93.5%) at on-site-diagnosis stage. We achieved an HCV RNA testing rate of 92.4% (254/275), an HCV treatment rate of 95.8% (203/212) and a sustained virological response rate of 94.1% (191/203). The collaborative referral model is highly effective in HCV RNA testing and HCV treatment uptake among MMT patients, achieving HCV micro-elimination.

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Groundwater and mud inrush disaster from completely weathered granite presents a huge difficulty for tunnel construction, which requires the grouting measurement with favorable performance. To propose the optimal material parameters for grouting, numerous tests, including strength, permeability, and anti-washout, were conducted to evaluate the effects of grouting filling ratio (GFR), curing age and water velocity on the grouting effect. The test results show that: (1) The hydraulic property of completely weathered granite can be significantly improved by increasing the grouting volume and curing age. In particular, when GFR ≥ 48%, the cohesion and internal friction angle increased to about 200 kPa and 30°, which were more than three and ten times of that pre-grouting. (2) With the increase of GFR, the permeability exhibited three stages: Slowly decreasing stage, sharply decreasing stage and stable stage. When increased from 32% to 48%, the permeability coefficient sharply decreased two orders of magnitude, namely from 4.05 × 10−5 cm/s to 1 × 10−7 cm/s. (3) The particle erosion rate decreased sharply to below 10% in the low water velocity (v ≤ 0.2 m/s) when GFR ≥ 48%, but still exceeded 50% when v ≥ 0.4m/s. The results indicated that the grouting volume of GFR = 48% was a suitable grouting parameter to reinforce the completely weathered granite, particularly in the low water velocity condition. The field investigation of hydraulic-mechanical behaviors in the Junchang tunnel indicated that the grouting effect can be improved markedly.