Objectives: Enterovirus 71 (EV71) is the major pathogen of hand, foot, and mouth disease and can cause death; however, its pathogenesis remains elusive. Methods: We performed a detailed systematic histopathologic examination and molecular studies on six autopsy cases of EV71 infection using H&E, immunohistochemistry, double immunofluorescence staining, and nested reverse transcription polymerase chain reaction. Results: Characteristic features of acute encephalomyelitis were observed. Viral antigens were mainly detected in neuronal cytoplasm and processes in the different brainstem nuclei and spinal cord, including the anterior and posterior horn cells. Viral antigens were also positive in the nerve roots of spinal cord and autonomic ganglia of intestines. Conclusions: Our study revealed direct pathologic evidence supporting viral entry into the central nervous system (CNS) through peripheral nerves. In addition to the major motor pathway, EV71 can also enter the CNS via peripheral sensory and autonomic pathways in retrograde axonal transport.

The glymphatic system theory introduces a new perspective on fluid flow and homeostasis in the brain. Here, cerebrospinal fluid and interstitial fluid (CSF-ISF) moves from the perivascular spaces (PVS) of arteries to those of veins for drainage. Aquaporin-4 (AQP4) plays a crucial role in driving fluid within the PVS. The impairment to AQP4 is closely linked to the dysfunction of the glymphatic system. The function of the glymphatic system is less active during waking but enhanced during sleep. The efficiency of the glymphatic system decreases with aging. Damage to the glymphatic system will give rise to the development and progression of many brain diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), chronic traumatic encephalopathy (CTE), and vascular dementia (VaD). Here, we reviewed previous research associated with the glymphatic system, including its concepts, principles, and influencing factors. We hypothesize that AQP4 could be a target for the prevention and treatment of certain brain diseases through the regulation on the glymphatic system.

Context: Terbufos (TBF) is a class Ia (extremely hazardous) organophosphate pesticide (OP) and its distribution in industrialized countries has been severely restricted. Thus, acute occupational poisoning is rather uncommon. However, it still occurs in rural areas of some developing countries, where the sale of TBF is not controlled and its use is thus not properly regulated. We report a case of a 43-year-old female farmer who died after applying TBF granules. Case: The patient died within 3 h after applying 20 bags of 5% TBF granules (900 g per bag). Investigation showed that her personal protective equipment (PPE) did not provide effective protection against dermal and inhalational exposure. Postmortem analysis revealed extremely low red blood cell acetylcholinesterase activity. Toxicological analysis of TBF showed 1.45 × 10⁻² μg/ml in the heart blood and 0.17 μg/g in the liver. Discussions: This patient died as a result of toxicity from dermal and inhalational exposure to TBF. Over-application, improper equipment, inadequate and defective PPE, and lack of hygienic precautions were all contributing factors. Conclusions: TBF is a highly toxic OP. Inadequate regulatory control, improper environmental application, and ineffective PPE resulted in a fatal human exposure.