Buqi Huoxue Tongnao prescription protects against chronic cerebral hypoperfusion via regulating PI3K/AKT and LXRα/CYP7A1 signaling pathways.

BACKGROUND: Chronic cerebral hypoperfusion (CCH) has been confirmed as one of the pathogenesis underlying vascular cognitive impairment. A series of pathological changes, including inflammation, oxidative stress, and apoptosis, are involved in this pathophysiology and contribute to cognitive impairment and neuropathological alterations. The traditional Chinese medicine (TCM) of Buqi Huoxue Tongnao (BQHXTN) prescription possesses a remarkable clinical efficacy for treating patients with CCH, but still lacks a scientific foundation for its pharmacological mechanisms. PURPOSE: To investigate the role and underlying mechanism of the effects of BQHXTN on CCH both in vitro and in vivo. METHODS: In this study, we established a two-vessel occlusion (2-VO) induced CCH model in Sprague-Dawley rats, an oxygen-glucose deprivation model in BV2 cells, and a steatosis cell model in L02 cells to reveal the underlying mechanisms of BQHXTN by behavioral test, histopathological analysis and the detection of pro-inflammatory cytokine, apoptotic factors and reactive oxide species. Donepezil hydrochloride and Buyang Huanwu decoction were used as positive drugs. RESULTS: Compared with the 2-VO group, BQHXTN treatment at three doses significantly enhanced the memory and learning abilities in the Y-maze and novel object recognition tests. The hematoxylin-eosin staining indicated that BQHXTN protected against hippocampal injury induced by CCH. Of note, in both in vivo and in vitro experiments, BQHXTN prominently inhibited the production of IL-1ß, TNF-α, cleaved-caspase 3, and iNOS by regulating the PI3K/AKT pathway, consequently exerting anti-inflammatory, anti-apoptotic, and antioxidant effects. Moreover, it provided the first initial evidence that BQHXTN treatment mitigated dyslipidemia by increasing the LXRα/CYP7A1 expression, thereby delaying the neuropathological process. CONCLUSION: In summary, these findings firstly revealed the pharmacodynamics and mechanism of BQHXTN, that is, BQHXTN could alleviate cognitive impairment, neuropathological alterations and dyslipidemia in CCH rats by activating PI3K/AKT and LXRα/CYP7A1 signaling pathways, as well as providing a TCM treatment strategy for CCH.

Tailoring Mechanical Properties of a Ceramic Nanowire Aerogel with Pyrolytic Carbon for In Situ Resilience at 1400 °C.

Resilient ceramic aerogels with a unique combination of lightweight, good high-temperature stability, high specific area, and thermal insulation properties are known for their promising applications in various fields. However, the mechanical properties of traditional ceramic aerogels are often constrained by insufficient interlocking of the building blocks. Here, we report a strategy to largely increase the interlocking degree of the building blocks by depositing a pyrolytic carbon (PyC) coating onto Si3N4 nanowires. The results show that the mechanical performances of the Si3N4 nanowire aerogels are intricately linked to the microstructure of the PyC nodes. The compression resilience of the Si3N4@PyC nanowire aerogels increases with an increase of the interlayer cross-linking in PyC. Additionally, benefiting from the excellent high-temperature stability of PyC, the Si3N4@PyC nanowire aerogels demonstrate significantly superior in situ resilience up to 1400 °C. The integrated mechanical and high-temperature properties of the Si3N4@PyC nanowire aerogels make them highly appealing for applications in harsh conditions. The facile method of manipulating the microstructure of the nodes may offer a perspective for tailoring the mechanical properties of ceramic aerogels.

Enhancing the performance of AlGaN-based DUV-LEDs with multifocal laser stealth dicing.

In this study, AlGaN-based deep-ultraviolet light-emitting diodes (DUV-LEDs) processed via standard laser dicing (SLD) and multifocal laser stealth dicing (MFLSD) were investigated. Adopting the MFLSD technology would generate a roughing surface rather than the V-shaped grooves on the sidewall of 508 × 508 µm2 DUV-LEDs, which would reduce the forward operating voltage and increase the wall-plug efficiency, light output power, and far-field radiation patterns of these devices. In addition, the wavelength shift, far-field patterns, and light-tracing simulation results of the DUV-LEDs processed with SLD and MFLSD were clearly demonstrated and analyzed. Accordingly, it was observed that the MFLSD process provided more possibilities for photon escape to increase the light extraction efficiency (LEE) of DUV-LEDs, thus decreased the wavelength-redshift and junction temperature in DUV-LEDs. These results provide a reference for advanced nano-processing practices implemented during the fabrication of semiconductor devices.

Constructing Microporous Ion Exchange Membranes via Simple Hypercrosslinking for pH-Neutral Aqueous Organic Redox Flow Batteries.

Ion exchange membranes (IEMs) play a critical role in aqueous organic redox flow batteries (AORFBs). Traditional IEMs that feature microphase-separated microstructures are well developed and easily available but suffer from the conductivity/selectivity tradeoff. The emerging charged microporous polymer membranes show the potential to overcome this tradeoff, yet their commercialization is still hindered by tedious syntheses and demanding conditions. We herein combine the advantages of these two types of membrane materials via simple in-situ hypercrosslinking of conventional IEMs into microporous ones. Such a concept is exemplified by the very cheap commercial quaternized polyphenylene oxide membrane. The hypercrosslinking treatment turns poor-performance membranes into high-performance ones, as demonstrated by the above 10-fold selectivity enhancement and much-improved conductivities that more than doubled. This turn is also confirmed by the effective and stable pH-neutral AORFB with decreased membrane resistance and at least an order of magnitude lower capacity loss rate. This battery shows advantages over other reported AORFBs in terms of a low capacity loss rate (0.0017% per cycle) at high current density. This work provides an economically feasible method for designing AORFB-oriented membranes with microporosity.

The association between hematologic traits and aneurysm-related subarachnoid hemorrhage: a two-sample mendelian randomization study.

Several hematologic traits have been suggested to potentially contribute to the formation and rupture of intracranial aneurysms (IA). The purpose of this study is to explore the causal association between hematologic traits and the risk of IA. To explore the causal association between hematologic traits and the risk of IA, we employed two-sample Mendelian randomization (MR) analysis. Two independent summary-level GWAS data were used for preliminary and replicated MR analyses. The inverse variance weighted (IVW) method was employed as the primary method in the MR analyses. The stabilities of the results were further confirmed by a meta-analysis. In the preliminary MR analysis, hematocrit, hemoglobin concentration (p = 0.0047), basophil count (p = 0.0219) had a suggestive inverse causal relationship with the risk of aneurysm-associated subarachnoid hemorrhage (aSAH). The monocyte percentage of white cells (p = 0.00956) was suggestively positively causally correlated with the risk of aSAH. In the replicated MR analysis, only the monocyte percentage of white cells (p = 0.00297) remained consistent with the MR results in the preliminary analysis. The hematocrit, hemoglobin concentration, and basophil count no longer showed significant causal relationship (p > 0.05). Meta-analysis results further confirmed that only the MR result of monocyte percentage of white cells reached significance in the random effect model and fixed effect model. None of the 25 hematologic traits was causally associated with the risk of unruptured intracranial aneurysms (uIA). This study revealed a suggestive positive association between the monocyte percentage of white cells and the risk of aSAH. This finding contributes to a better understanding that monocytes/macrophages could participate in the risk of aSAH.

The Potential of Multi-Task Learning in CFDST Design: Load-Bearing Capacity Design with Three MTL Models.

Concrete-filled double steel tubes (CFDSTs) are a load-bearing structure of composite materials. By combining concrete and steel pipes in a nested structure, the performance of the column will be greatly improved. The performance of CFDSTs is closely related to their design. However, existing codes for CFDST design often focus on how to verify the reliability of a design, but specific design parameters cannot be directly provided. As a machine learning technique that can simultaneously learn multiple related tasks, multi-task learning (MTL) has great potential in the structural design of CFDSTs. Based on 227 uniaxial compression cases of CFDSTs collected from the literature, this paper utilized three multi-task models (multi-task Lasso, VSTG, and MLS-SVR) separately to provide multiple parameters for CFDST design. To evaluate the accuracy of models, four statistical indicators were adopted (R2, RMSE, RRMSE, and ρ). The experimental results indicated that there was a non-linear relationship among the parameters of CFDSTs. Nevertheless, MLS-SVR was still able to provide an accurate set of design parameters. The coefficient matrices of two linear models, multi-task Lasso and VSTG, revealed the potential connection among CFDST parameters. The latent-task matrix V in VSTG divided the prediction tasks of inner tube diameter, thickness, strength, and concrete strength into three groups. In addition, the limitations of this study and future work are also summarized. This paper provides new ideas for the design of CFDSTs and the study of related codes.

Propofol Alleviates Anxiety-Like Behaviors Associated with Pain by Inhibiting the Hyperactivity of PVNCRH Neurons via GABAA Receptor ß3 Subunits.

Pain, a comorbidity of anxiety disorders, causes substantial clinical, social, and economic burdens. Emerging evidence suggests that propofol, the most commonly used general anesthetic, may regulate psychological disorders; however, its role in pain-associated anxiety is not yet described. This study investigates the therapeutic potential of a single dose of propofol (100 mg kg-1) in alleviating pain-associated anxiety and examines the underlying neural mechanisms. In acute and chronic pain models, propofol decreased anxiety-like behaviors in the elevated plus maze (EPM) and open field (OF) tests. Propofol also reduced the serum levels of stress-related hormones including corticosterone, corticotropin-releasing hormone (CRH), and norepinephrine. Fiber photometry recordings indicated that the calcium signaling activity of CRH neurons in the paraventricular nucleus (PVNCRH) is reduced after propofol treatment. Interestingly, artificially activating PVNCRH neurons through chemogenetics interfered with the anxiety-reducing effects of propofol. Electrophysiological recordings indicated that propofol decreases the activity of PVNCRH neurons by increasing spontaneous inhibitory postsynaptic currents (sIPSCs). Further, reducing the levels of γ-aminobutyric acid type A receptor ß3 (GABAAß3) subunits in PVNCRH neurons diminished the anxiety-relieving effects of propofol. In conclusion, this study provides a mechanistic and preclinical rationale to treat pain-associated anxiety-like behaviors using a single dose of propofol.

A potassium-chloride co-transporter with altered genome architecture functions as a suppressor in glioma.

Gliomas, the most lethal tumours in brain, have a poor prognosis despite accepting standard treatment. Limited benefits from current therapies can be attributed to genetic, epigenetic and microenvironmental cues that affect cell programming and drive tumour heterogeneity. Through the analysis of Hi-C data, we identified a potassium-chloride co-transporter SLC12A5 associated with disrupted topologically associating domain which was downregulated in tumour tissues. Multiple independent glioma cohorts were included to analyse the characterization of SLC12A5 and found it was significantly associated with pathological features, prognostic value, genomic alterations, transcriptional landscape and drug response. We constructed two SLC12A5 overexpression cell lines to verify the function of SLC12A5 that suppressed tumour cell proliferation and migration in vitro. In addition, SLC12A5 was also positively associated with GABAA receptor activity and negatively associated with pro-tumour immune signatures and immunotherapy response. Collectively, our study provides a comprehensive characterization of SLC12A5 in glioma and supports SLC12A5 as a potential suppressor of disease progression.

Dual-Function Electrolyte Additive Design for Long Life Alkaline Zinc Flow Batteries.

Alkaline zinc-based flow batteries (AZFBs) have emerged as a promising electrochemical energy storage technology owing to Zn abundance, high safety, and low cost. However, zinc dendrite growth and the formation of dead zinc greatly impede the development of AZFBs. Herein, a dual-function electrolyte additive strategy is proposed to regulate zinc nucleation and mitigate the hydroxide corrosion of zinc depositions for stable AZFBs. This strategy, as exemplified by urea, introduces an electrolyte additive to coordinate with Zn2+/Zn with proper strength, slowing zinc deposition kinetics to induce uniform nucleation and protecting the deposited zinc surface from attack by hydroxide ions through preferable adsorption. The zincate complexes with urea are identified to be Zn(OH)2(urea)(H2O)2 and Zn2(OH)4(H2O)4(urea), which exhibit slow zinc deposition kinetics, allowing instantaneous nucleation. Calculation results reveal an additional energy barrier of 1.29 eV for the subsequent adsorption of an OH- group when a urea molecule absorbs on the zinc cluster, significantly mitigating the formation of dead zinc. Consequently, prolonged cell cycling of the prototype alkaline zinc-iron flow battery demonstrates stable operation for over 130 h and an average coulombic efficiency of 98.5%. It is anticipated that this electrolyte additive strategy will pave the way for developing highly stable AZFBs.

[Efficacy and Mechanism of Tetracycline Adsorption by Boron-doped Mesoporous Carbon].

Using coconut shell and boric acid as raw materials， a new boron-doped coconut shell mesoporous carbon material （B-CSC） was prepared using a simple one-step pyrolysis method for efficient adsorption and removal of tetracycline pollutants in water. The effects of pyrolysis temperature and boron-carbon mass ratio on the adsorption performance under key preparation conditions were systematically studied， and their microstructure and physicochemical properties were characterized using a specific surface area and pore size analyzer （BET）， field emission scanning electron microscopy （SEM）， X-ray photon spectroscopy （XPS）， Raman spectrometer （Raman）， and Zeta potentiometer （Zeta）. The effects of initial pH， different metal cations， and different background water quality conditions on the adsorption effect were systematically investigated. Combined with material characterization and correlation analysis， the enhanced adsorption mechanism was discussed and analyzed in depth. The results showed that one-step pyrolysis could incorporate boron into the surface and crystal lattice of coconut shell charcoal， resulting in a larger specific surface area and pore volume， and the main forms of boron introduced were H3BO3， B2O3， B， and B4C. The adsorption capacity of B-CSC to tetracycline reached 297.65 mg·g-1， which was 8.9 times that of the original coconut shell mesoporous carbon （CSC）. At the same time， the adsorption capacity of B-CSC for rhodamine B （RhB）， bisphenol A（BPA）， and methylene blue （MB）， common pollutants in aquatic environments， was as high as 372.65， 255.24， and 147.82 mg·g-1， respectively. The adsorption process of B-CSC to tetracycline was dominated by physicochemical interaction， mainly involving liquid film diffusion， surface adsorption， mesoporous and microporous diffusion， and active site adsorption， and H3BO3 was the main adsorption site. The adsorption strengthening mechanism mainly reduced the chemical inertness of the carbon network and enhanced its π-π interaction and hydrogen bonding with tetracycline molecules.

Machine learning-based investigation of regulated cell death for predicting prognosis and immunotherapy response in glioma patients.

Glioblastoma is a highly aggressive and malignant type of brain cancer that originates from glial cells in the brain, with a median survival time of 15 months and a 5-year survival rate of less than 5%. Regulated cell death (RCD) is the autonomous and orderly cell death under genetic control, controlled by precise signaling pathways and molecularly defined effector mechanisms, modulated by pharmacological or genetic interventions, and plays a key role in maintaining homeostasis of the internal environment. The comprehensive and systemic landscape of the RCD in glioma is not fully investigated and explored. After collecting 18 RCD-related signatures from the opening literature, we comprehensively explored the RCD landscape, integrating the multi-omics data, including large-scale bulk data, single-cell level data, glioma cell lines, and proteome level data. We also provided a machine learning framework for screening the potentially therapeutic candidates. Here, based on bulk and single-cell sequencing samples, we explored RCD-related phenotypes, investigated the profile of the RCD, and developed an RCD gene pair scoring system, named RCD.GP signature, showing a reliable and robust performance in predicting the prognosis of glioblastoma. Using the machine learning framework consisting of Lasso, RSF, XgBoost, Enet, CoxBoost and Boruta, we identified seven RCD genes as potential therapeutic targets in glioma and verified that the SLC43A3 highly expressed in glioma grades and glioma cell lines through qRT-PCR. Our study provided comprehensive insights into the RCD roles in glioma, developed a robust RCD gene pair signature for predicting the prognosis of glioma patients, constructed a machine learning framework for screening the core candidates and identified the SLC43A3 as an oncogenic role and a prediction biomarker in glioblastoma.

A series of high-sensitivity radon detection systems and their applications in nitrogen as well as the boil-off liquid nitrogen measurement.

In modern rare-event search experiments such as neutrino experiments and dark matter search experiments, radon is one of the most important radiation backgrounds since it can emanate from nearly all the materials containing radium and migrate freely in the experiment system. To support the China Dark Matter Experiment (CDEX) at China Jinping Underground Laboratory (CJPL), a series of high-sensitivity radon detection systems with different electrostatic collection chambers were designed, and radon in nitrogen as well as boil-off liquid nitrogen was measured after accurate calibration and enrichment. Results showed that the calibration factors were 2.1 ± 0.2 (counts/h)/(Bq/m3), 21.1 ± 0.7 (counts/h)/(Bq/m3), 186.2 ± 2.2 (counts/h)/(Bq/m3), 387 ± 7 (counts/h)/(Bq/m3) and the 90% confidence level detection limits were 27.22 mBq/m3, 1.89 ∼ 3.06 mBq/m3, 0.41 ∼ 0.68 mBq/m3, 0.44 mBq/m3 for CJPL-HR2, CJPL-HR20, CJPL-HR140 and CJPL-HR300 measurement systems, respectively. Combined with an enrichment system consisting of twenty g CarboACT activated charcoals in a cold trap, the lower level detection limit (LLD) of typical No.1 CJPL-HR140 could reach 1.8 µBq/m3 with three days' enrichment time and three days' measurement time at 20 L/min sampling flowrate. For verification and application, the radon activity concentrations in nitrogen were 0.6 ∼ 1.9 mBq/m3 with an average of 1.1 ± 0.1 mBq/m3.While in boil-off liquid nitrogen, the radon activity concentrations ranged from 0.04 to 0.62 mBq/m3, and they were significantly lower in old-decayed liquid nitrogen compared to newly-filled liquid nitrogen, with a nearly five-fold decrease.

Polarized Ultrathin BN Induced Dynamic Electron Interactions for Enhancing Acidic Oxygen Evolution.

Developing ruthenium-based heterogeneous catalysts with an efficient and stable interface is essential for enhanced acidic oxygen evolution reaction (OER). Herein, we report a defect-rich ultrathin boron nitride nanosheet support with relatively independent electron donor and acceptor sites, which serves as an electron reservoir and receiving station for RuO2, realizing the rapid supply and reception of electrons. Through precisely controlling the reaction interface, a low OER overpotential of only 180 mV (at 10 mA cm-2) and long-term operational stability (350 h) are achieved, suggesting potential practical applications. In situ characterization and theoretical calculations have validated the existence of a localized electronic recycling between RuO2 and ultrathin BN nanosheets (BNNS). The electron-rich Ru sites accelerate the adsorption of water molecules and the dissociation of intermediates, while the interconnection between the O-terminal and B-terminal edge establishes electronic back-donation, effectively suppressing the over-oxidation of lattice oxygen. This study provides a new perspective for constructing a stable and highly active catalytic interface.

A highly integrated digital PCR system with on-chip heating for accurate DNA quantitative analysis.

Digital polymerase chain reaction (dPCR) is extensively used for highly sensitive disease diagnosis due to its single-molecule detection ability. However, current dPCR systems require intricate DNA sample distribution, rely on cumbersome external heaters, and exhibit sluggish thermal cycling, hampering efficiency and speed of the dPCR process. Herein, we presented the development of a microwell array based dPCR system featuring an integrated self-heating dPCR chip. By utilizing hydrodynamic and electrothermal simulations, the chip's structure is optimized, resulting in improved partitioning within microwells and uniform thermal distribution. Through strategic hydrophilic/hydrophobic modifications on the chip's surface, we effectively secured the compartmentalization of sample within the microwells by employing an overlaying oil phase, which renders homogeneity and independence of samples in the microwells. To achieve precise, stable, uniform, and rapid self-heating of the chip, the ITO heating layer and the temperature control algorithm are deliberately designed. With a capacity of 22,500 microwells that can be easily expanded, the system successfully quantified EGFR plasmid solutions, exhibiting a dynamic linear range of 105 and a detection limit of 10 copies per reaction. To further validate its performance, we employed the dPCR platform for quantitative detection of BCR-ABL1 mutation gene fragments, where its performance was compared against the QuantStudio 3D, and the self-heating dPCR system demonstrated similar analytical accuracy to the commercial dPCR system. Notably, the individual chip is produced on a semiconductor manufacturing line, benefiting from mass production capabilities, so the chips are cost-effective and conducive to widespread adoption and accessibility.

Supervised training models with or without manual lesion delineation outperform clinicians in distinguishing pulmonary cryptococcosis from lung adenocarcinoma on chest CT.

BACKGROUND: The role of artificial intelligence (AI) in the discrimination between pulmonary cryptococcosis (PC) and lung adenocarcinoma (LA) warrants further research. OBJECTIVES: To compare the performances of AI models with clinicians in distinguishing PC from LA on chest CT. METHODS: Patients diagnosed with confirmed PC or LA were retrospectively recruited from three tertiary hospitals in Guangzhou. A deep learning framework was employed to develop two models: an undelineated supervised training (UST) model utilising original CT images, and a delineated supervised training (DST) model utilising CT images with manual lesion annotations provided by physicians. A subset of 20 cases was randomly selected from the entire dataset and reviewed by clinicians through a network questionnaire. The sensitivity, specificity and accuracy of the models and the clinicians were calculated. RESULTS: A total of 395 PC cases and 249 LA cases were included in the final analysis. The internal validation results for the UST model showed a sensitivity of 85.3%, specificity of 81.0%, accuracy of 83.6% and an area under the curve (AUC) of 0.93. Similarly, the DST model exhibited a sensitivity of 88.2%, specificity of 88.1%, accuracy of 88.2% and an AUC of 0.94. The external validation of the two models yielded AUC values of 0.74 and 0.77, respectively. The average sensitivity, specificity and accuracy of 102 clinicians were determined to be 63.1%, 53.7% and 59.3%, respectively. CONCLUSIONS: Both models outperformed the clinicians in distinguishing between PC and LA on chest CT, with the UST model exhibiting comparable performance to the DST model.

Hospitalization, case fatality, comorbidities, and isolated pathogens of adult inpatients with pneumonia from 2013 to 2022: a real-world study in Guangzhou, China.

BACKGROUND: In the context of increasing population aging, ongoing drug-resistant pathogens and the COVID-19 epidemic, the changes in the epidemiological and clinical characteristics of patients with pneumonia remain unclear. This study aimed to assess the trends in hospitalization, case fatality, comorbidities, and isolated pathogens of pneumonia-related adult inpatients in Guangzhou during the last decade. METHODS: We retrospectively enrolled hospitalized adults who had doctor-diagnosed pneumonia in the First Affiliated Hospital of Guangzhou Medical University from January 1, 2013 to December 31, 2022. A natural language processing system was applied to automatically extract the clinical data from electronic health records. We evaluated the proportion of pneumonia-related hospitalizations in total hospitalizations, pneumonia-related in-hospital case fatality, comorbidities, and species of isolated pathogens during the last decade. Binary logistic regression analysis was used to assess predictors for patients with prolonged length of stay (LOS). RESULTS: A total of 38,870 cases were finally included in this study, with 70% males, median age of 64 (53, 73) years and median LOS of 7.9 (5.1, 12.8) days. Although the number of pneumonia-related hospitalizations showed an upward trend, the proportion of pneumonia-related hospitalizations decreased from 199.6 per 1000 inpatients in 2013 to 123.4 per 1000 in 2021, and the case fatality decreased from 50.2 per 1000 in 2013 to 23.9 per 1000 in 2022 (all P < 0.05). The most common comorbidities were chronic obstructive pulmonary disease, lung malignancy, cardiovascular diseases and diabetes. The most common pathogens were Pseudomonas aeruginosa, Candida albicans, Acinetobacter baumannii, Stenotrophomonas maltophilia, Klebsiella pneumoniae, and Staphylococcus aureus. Glucocorticoid use during hospitalization (Odd Ratio [OR] = 1.86, 95% Confidence Interval (CI): 1.14-3.06), immunosuppressant use during hospitalization (OR = 1.99, 1.14-3.46), ICU admission (OR = 16.23, 95%CI: 11.25-23.83), receiving mechanical ventilation (OR = 3.58, 95%CI: 2.60-4.97), presence of other underlying diseases (OR = 1.54, 95%CI: 1.15-2.06), and elevated procalcitonin (OR = 1.61, 95%CI: 1.19-2.19) were identified as independent predictors for prolonged LOS. CONCLUSION: The proportion of pneumonia-related hospitalizations and the in-hospital case fatality showed downward trends during the last decade. Pneumonia inpatients were often complicated by chronic underlying diseases and isolated with gram-negative bacteria. ICU admission was a significant predictor for prolonged LOS in pneumonia inpatients.

Treatment of primary aldosteronism: Clinical practice guidelines of the Taiwan Society of Aldosteronism.

Primary aldosteronism (PA) is the most common cause of secondary hypertension and one of the few medical diseases that can be cured by surgery. Excessive aldosterone secretion is highly associated with cardiovascular complications. Many studies have shown that patients with unilateral PA treated with surgery have better survival, cardiovascular, clinical, and biochemical outcomes than those who receive medical treatment. Consequently, laparoscopic adrenalectomy is the gold standard for treating unilateral PA. Surgical methods should be individualized according to the patient's tumor size, body shape, surgical history, wound considerations, and surgeon's experience. Surgery can be performed through a transperitoneal or retroperitoneal approach, and via a single-port or multi-port laparoscopic approach. However, total or partial adrenalectomy remains controversial in treating unilateral PA. Partial excision will not completely eradicate the disease and is prone to recurrence. Mineralocorticoid receptor antagonists should be considered for patients with bilateral PA or patients who cannot undergo surgery. There are also emerging alternative interventions, including radiofrequency ablation and transarterial adrenal ablation, for which data on long-term outcomes are currently lacking. The Task Force of Taiwan Society of Aldosteronism developed these clinical practice guidelines with the aim of providing medical professionals with more updated information on the treatment of PA and improving the quality of care.

Esketamine accelerates emergence from isoflurane general anaesthesia by activating the paraventricular thalamus glutamatergic neurones in mice.

BACKGROUND: Delayed emergence from general anaesthesia poses a significant perioperative safety hazard. Subanaesthetic doses of ketamine not only deepen anaesthesia but also accelerate recovery from isoflurane anaesthesia; however, the mechanisms underlying this phenomenon remain elusive. Esketamine exhibits a more potent receptor affinity and fewer adverse effects than ketamine and exhibits shorter recovery times after brief periods of anaesthesia. As the paraventricular thalamus (PVT) plays a pivotal role in regulating wakefulness, we studied its role in the emergence process during combined esketamine and isoflurane anaesthesia. METHODS: The righting reflex and cortical electroencephalography were used as measures of consciousness in mice during isoflurane anaesthesia with coadministration of esketamine. The expression of c-Fos was used to determine neuronal activity changes in PVT neurones after esketamine administration. The effect of esketamine combined with isoflurane anaesthesia on PVT glutamatergic (PVTGlu) neuronal activity was monitored by fibre photometry, and chemogenetic technology was used to manipulate PVTGlu neuronal activity. RESULTS: A low dose of esketamine (5 mg kg-1) accelerated emergence from isoflurane general anaesthesia (474 [30] s vs 544 [39] s, P=0.001). Esketamine (5 mg kg-1) increased PVT c-Fos expression (508 [198] vs 258 [87], P=0.009) and enhanced the population activity of PVTGlu neurones (0.03 [1.7]% vs 6.9 [3.4]%, P=0.002) during isoflurane anaesthesia (1.9 [5.7]% vs -5.1 [5.3]%, P=0.016) and emergence (6.1 [6.2]% vs -1.1 [5.0]%, P=0.022). Chemogenetic suppression of PVTGlu neurones abolished the arousal-promoting effects of esketamine (459 [33] s vs 596 [33] s, P<0.001). CONCLUSIONS: Our results suggest that esketamine promotes recovery from isoflurane anaesthesia by activating PVTGlu neurones. This mechanism could explain the rapid arousability exhibited upon treatment with a low dose of esketamine.

The predictors of long-term outcomes after targeted therapy for primary Aldosteronism.

Unilateral primary aldosteronism is thought to be a surgically curable disease, and unilateral adrenalectomy is the mainstay treatment. The Primary Aldosteronism Surgical Outcome (PASO) consensus was developed to assess clinical and biochemical outcomes to standardize the classification of surgical outcomes. However, fewer than half of patients are cured of hypertension after adrenalectomy; therefore, preoperative patient counseling and evaluation might be necessary. Moreover, current studies show that genetic mutations and histopathology classification are associated with the treatment outcome. The Task Force of Taiwan PA recommends using a specific scoring system, including the PASO score and nomogram-based preoperative score, to predict the clinical outcome before adrenalectomy. Herein, we discuss the associations of current histopathological classification and specific somatic gene mutations with clinical outcomes after surgery.