Studies in rodents revealed that selective accumulation of Na+ channel subtypes at the axon initial segment (AIS) determines action potential (AP) initiation and backpropagation in cortical pyramidal cells (PCs); however, in human cortex, the molecular identity of Na+ channels distributed at PC axons, including the AIS and the nodes of Ranvier, remains unclear. We performed immunostaining experiments in human cortical tissues removed surgically to cure brain diseases. We found strong immunosignals of Na+ channels and two channel subtypes, NaV1.2 and NaV1.6, at the AIS of human cortical PCs. Although both channel subtypes were expressed along the entire AIS, the peak immunosignals of NaV1.2 and NaV1.6 were found at proximal and distal AIS regions, respectively. Surprisingly, in addition to the presence of NaV1.6 at the nodes of Ranvier, NaV1.2 was also found in a subpopulation of nodes in the adult human cortex, different from the absence of NaV1.2 in myelinated axons in rodents. NaV1.1 immunosignals were not detected at either the AIS or the nodes of Ranvier of PCs; however, they were expressed at interneuron axons with different distribution patterns. Further experiments revealed that parvalbumin-positive GABAergic axon cartridges selectively innervated distal AIS regions with relatively high immunosignals of NaV1.6 but not the proximal NaV1.2-enriched compartments, suggesting an important role of axo-axonic cells in regulating AP initiation in human PCs. Together, our results show that both NaV1.2 and NaV1.6 (but not NaV1.1) channel subtypes are expressed at the AIS and the nodes of Ranvier in adult human cortical PCs, suggesting that these channel subtypes control neuronal excitability and signal conduction in PC axons.

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The present evidences indicated that the motion-preservation procedures had an advantage on reducing the prevalence of ASDeg, ASDis and the reoperation rate due to the adjacent segment degeneration compared with the lumbar fusion. And the clinical outcomes of the two procedures are similar.

Peroral endoscopic myotomy (POEM) has been widely applied to the treatment of achalasia. The aim of this study is to retrospectively investigate the long-term outcome of POEM in patients with achalasia. Patients undergoing POEM at our center with a minimum follow-up of 3 years were enrolled in this study. Relief of patients' symptom was defined as the primary outcome. Secondary outcomes included lower esophageal sphincter pressure, esophageal emptying, symptoms relapse, and clinical reflux adverse events. The Chi-square test was performed to determine the potential predictors of surgical failure. Sixty-seven patients (aged 40.7 ± 15.3 years) were recruited in the study, with a mean follow-up period of 40.1 ± 2.8 months. At the final follow-up, the median Eckardt score reduced from 7.6 ± 2.3 preoperatively to 1.9 ± 1.7 (P < 0.001), the lower esophageal sphincter pressure was reduced from 35.4 ± 13.7 mmHg preoperatively to 8.9 ± 4.1 mmHg (P < 0.001), and the height of the barium column at 5 min after barium swallowed was reduced from 9.7 ± 1.6 cm preoperatively to 2.9 ± 2.1 cm (P < 0.001). Eight patients had symptoms relapse and nine patients developed reflux esophagitis. Type III achalasia was found to be indicative of surgical failure. POEM was a promising treatment for patients with achalasia, which can yield a long-term relief of the symptom and a low rate of clinical reflux adverse events.

POEM is an effective approach for treating achalasia, which can relieve the symptoms of achalasia by improving esophageal emptying and lowering LES pressure.