A robust localization approach for Percutaneous Nephrolithotomy (PCNL): A single-center retrospective study.

BACKGROUND: Percutaneous Nephrolithotomy (PCNL) represents the gold standard treatment method for cases with large kidney stones. As a critical step in performing PCNL, the procedure of establishing a safe and accurate nephrostomy tract will dramatically impact the treatment quality of patients with large-sized kidney stones. OBJECTIVE: This work attempts to describe a new and improved process of establishing an accurate nephrostomy tract and clinically evaluate the effectiveness and safeness of this proposed methodology. METHODS: This work represents a retrospective single-center study carried out between August 2013 and November 2019. The collected samples consist of 937 patients who were operated on using PCNL coupled with our proposed procedure. Briefly, a preoperative B-ultrasonography was firstly performed to decide the puncture point in a simulated surgical position where was marked with ureteral catheter segments (2-3 cm). A computed tomography (CT) scan was followed to correct the anchor points in the simulated surgical position. After this, an accurate puncture operation was performed under the real-time guidance of intraoperative B ultrasound. RESULTS: Examining this study, 851 subjects with renal stones and 86 subjects with ureteropelvic junction stones were included for the PCNL operation project. All samples were grouped with Guy's grading system: grade I, II, III, and IV patients there were 0.00%, 42.69%, 51.01%, and 6.30%, respectively. Among these patients, the average age was 48.49 ± 10.80 years old, with a male to female ratio of around 1.73:1. CONCLUSIONS: This study showed that our developed method warrants an accurate and safe PCNL operation that involves the process of establishing the nephrostomy tract. Other advantageous attributes of this new PCNL process include negligible radiation exposure, lesser complications, and low failure rates. More importantly, this new localization approach is particularly attractive for hospitals that are new to the field of adopting PCNL considering its safeness, effectiveness, and learnability.

Prefrontal GABAA(δ)R Promotes Fear Extinction through Enabling the Plastic Regulation of Neuronal Intrinsic Excitability.

Extinguishing the previously acquired fear is critical for the adaptation of an organism to the ever-changing environment, a process requiring the engagement of GABAA receptors (GABAARs). GABAARs consist of tens of structurally, pharmacologically, and functionally heterogeneous subtypes. However, the specific roles of these subtypes in fear extinction remain largely unexplored. Here, we observed that in the medial prefrontal cortex (mPFC), a core region for mood regulation, the extrasynaptically situated, δ-subunit-containing GABAARs [GABAA(δ)Rs], had a permissive role in tuning fear extinction in male mice, an effect sharply contrasting to the established but suppressive role by the whole GABAAR family. First, the fear extinction in individual mice was positively correlated with the level of GABAA(δ)R expression and function in their mPFC. Second, knockdown of GABAA(δ)R in mPFC, specifically in its infralimbic (IL) subregion, sufficed to impair the fear extinction in mice. Third, GABAA(δ)R-deficient mice also showed fear extinction deficits, and re-expressing GABAA(δ)Rs in the IL of these mice rescued the impaired extinction. Further mechanistic studies demonstrated that the permissive effect of GABAA(δ)R was associated with its role in enabling the extinction-evoked plastic regulation of neuronal excitability in IL projection neurons. By contrast, GABAA(δ)R had little influence on the extinction-evoked plasticity of glutamatergic transmission in these cells. Altogether, our findings revealed an unconventional and permissive role of extrasynaptic GABAA receptors in fear extinction through a route relying on nonsynaptic plasticity.SIGNIFICANCE STATEMENT The medial prefrontal cortex (mPFC) is one of the kernel brain regions engaged in fear extinction. Previous studies have repetitively shown that the GABAA receptor (GABAAR) family in this region act to suppress fear extinction. However, the roles of specific GABAAR subtypes in mPFC are largely unknown. We observed that the GABAAR-containing δ-subunit [GABAA(δ)R], a subtype of GABAARs exclusively situated in the extrasynaptic membrane and mediating the tonic neuronal inhibition, works oppositely to the whole GABAAR family and promotes (but does not suppress) fear extinction. More interestingly, in striking contrast to the synaptic GABAARs that suppress fear extinction by breaking the extinction-evoked plasticity of glutamatergic transmission, the GABAA(δ)R promotes fear extinction through enabling the plastic regulation of neuronal excitability in the infralimbic subregion of mPFC. Our findings thus reveal an unconventional role of GABAA(δ)R in promoting fear extinction through a route relying on nonsynaptic plasticity.

Chronic Stress Oppositely Regulates Tonic Inhibition in Thy1-Expressing and Non-expressing Neurons in Amygdala.

Chronic or prolonged exposure to stress ranks among the most important socioenvironmental factors contributing to the development of neuropsychiatric diseases, a process generally associated with loss of inhibitory tone in amygdala. Recent studies have identified distinct neuronal circuits within the basolateral amygdala (BLA) engaged in different emotional processes. However, the potential circuit involved in stress-induced dysregulation of inhibitory tones in BLA remains elusive. Here, a transgenic mouse model expressing yellow fluorescent protein under control of the Thy1 promoter was used to differentiate subpopulations of projection neurons (PNs) within the BLA. We observed that the tonic inhibition in amygdala neurons expressing and not expressing Thy1 (Thy1+/-) was oppositely regulated by chronic social defeat stress (CSDS). In unstressed control mice, the tonic inhibitory currents were significantly stronger in Thy1- PNs than their Thy1+ counterparts. CSDS markedly reduced the currents in Thy1- projection neurons (PNs), but increased that in Thy1+ ones. By contrast, CSDS failed to affect both the phasic A-type γ-aminobutyric acid receptor (GABAAR) currents and GABABR currents in these two PN populations. Moreover, chronic corticosterone administration was sufficient to mimic the effect of CSDS on the tonic inhibition of Thy1+ and Thy1- PNs. As a consequence, the suppression of tonic GABAAR currents on the excitability of Thy1- PNs was weakened by CSDS, but enhanced in Thy1+ PNs. The differential regulation of chronic stress on the tonic inhibition in Thy1+ and Thy1- neurons may orchestrate cell-specific adaptation of amygdala neurons to chronic stress.