Astrocytic HILPDA promotes lipid droplets generation to drive cognitive dysfunction in mice with sepsis-associated encephalopathy.

AIMS: Sepsis-associated encephalopathy (SAE) is manifested as a spectrum of disturbed cerebral function ranging from mild delirium to coma. However, the pathogenesis of SAE has not been clearly elucidated. Astrocytes play important roles in maintaining the function and metabolism of the brain. Most recently, it has been demonstrated that disorders of lipid metabolism, especially lipid droplets (LDs) dyshomeostasis, are involved in a variety of neurodegenerative diseases. The aim of this study was to investigate whether LDs are involved in the underlying mechanism of SAE. METHODS: The open field test, Y-maze test, and contextual fear conditioning test (CFCT) were used to test cognitive function in SAE mice. Lipidomics was utilized to investigate alterations in hippocampal lipid metabolism in SAE mice. Western blotting and immunofluorescence labeling were applied for the observation of related proteins. RESULTS: In the current study, we found that SAE mice showed severe cognitive dysfunction, including spatial working and contextual memory. Meanwhile, we demonstrated that lipid metabolism was widely dysregulated in the hippocampus by using lipidomic analysis. Furthermore, western blotting and immunofluorescence confirmed that LDs accumulation in hippocampal astrocytes was involved in the pathological process of cognitive dysfunction in SAE mice. We verified that LDs can be inhibited by specifically suppress hypoxia-inducible lipid droplet-associated protein (HILPDA) in astrocytes. Meanwhile, cognitive dysfunction in SAE was ameliorated by reducing A1 astrocyte activation and inhibiting presynaptic membrane transmitter release. CONCLUSION: The accumulation of astrocytic lipid droplets plays a crucial role in the pathological process of SAE. HILPDA is an attractive therapeutic target for lipid metabolism regulation and cognitive improvement in septic patients.

Clinical characteristics of patients with a risk of pulmonary artery hypertension secondary to ARDS in a high-altitude area.

BACKGROUND: Hypoxaemia plays an important role in the development of pulmonary artery hypertension (PAH). Patients with acute respiratory distress syndrome (ARDS) in a high-altitude area have different pathophysiological characteristics from those patients in the plains. The goal of our study was to explore the clinical characteristics of PAH secondary to ARDS in a high-altitude area. METHODS: This was a prospective study conducted in the affiliated Hospital of Qinghai University. Two investigators independently assessed pulmonary artery pressure (PAP) and right ventricular function by transthoracic echocardiography. Basic information and clinical data of the patients who were enrolled were collected. A multivariable logistic regression model was used to evaluate the risk factors for PAH secondary to ARDS in the high-altitude area. RESULTS: The incidence of PAH secondary to ARDS within 48 hours in the high-altitude area was 44.19%. Partial pressure of oxygen/fraction of inspired oxygen <165.13 mm Hg was an independent risk factor for PAH secondary to ARDS in the high-altitude area. Compared with the normal PAP group, the right ventricular basal dimensions were significantly larger and the right ventricular tricuspid annular plane systolic excursion was lower in the PAH group (right ventricular basal dimensions: 45.47±2.60 vs 40.67±6.12 mm, p=0.019; tricuspid annular plane systolic excursion (TAPSE): 1.82±0.40 vs 2.09±0.32 cm, p=0.021). The ratio of TAPSE to systolic PAP was lower in the PAH group (0.03±0.01 vs 0.08±0.03 cm/mm Hg, p<0.001). CONCLUSIONS: The incidence of PAH in patients with ARDS in our study is high. PAH secondary to ARDS in a high-altitude area could cause right ventricular dysfunction. TRIAL REGISTRATION NUMBER: NCT05166759.

Effects of Nalbuphine on Gastrointestinal Function in Post-Operative Critical Ill Patients Admitted to the ICU: A Multicenter Randomized Controlled Trial.

BACKGROUND: Gastrointestinal (GI) function can be a significant problem in critically ill patients and is associated with detrimental outcomes. The administration of opioids for pain reduction is thought to contribute to GI dysfunction. We tested whether nalbuphine, a mixed agonist/antagonist opioid modulator, can promote GI recovery in postoperative critical patients admitted to the intensive care unit (ICU) and compared it with fentanyl, a selective mu opioid receptor (MOR) agonist. METHODS: This is a multicenter, single-blind, randomized controlled trial to investigate whether nalbuphine improves the GI recovery in ICU patients after surgery, and compared it with fentanyl. The primary outcome was the time to first defecation. Secondary outcomes included the use of sedatives, enemas or laxatives, the acute gastrointestinal injury (AGI) grade, the incidence of vomiting, and the lengths of ICU and hospital stays. RESULTS: We randomized 436 patients, and a total of 369 patients were included in the modified intention-to-treat population (mITT) (185 to the nalbuphine group and 184 to the fentanyl group). The baseline demographic characteristics of the two groups were comparable after randomization. There was no significant difference in the time to defecation between the two groups [hazard ratio (HR) 0.94, 95% CI 0.74-1.19, p = 0.62]. There was no significant difference in the secondary outcomes between the two groups. CONCLUSION: We found no evidence that nalbuphine administration can improve the GI function in postoperative critical patients admitted to the ICU compared with fentanyl. However, the CI was wide and we could not exclude the clinically important difference.

Definition of Acute Respiratory Distress Syndrome on the Plateau of Xining, Qinghai: A Verification of the Berlin Definition Altitude-PaO2/FiO2-Corrected Criteria.

Background: Acute respiratory distress syndrome (ARDS) is a common critical respiratory illness. Hypoxia at high altitude is a factor that influences the progression of ARDS. Currently, we lack clear diagnostic criteria for high-altitude ARDS. The purpose of this study was to determine the value of the application of the Berlin Definition altitude-PaO2/FiO2-corrected criteria for ARDS in Xining, Qinghai (2,261 m). Methods: We retrospectively analyzed the clinical data of patients with ARDS admitted to the Department of Critical Care Medicine of the Affiliated Hospital of Qinghai University from January 2018 to December 2018. The severity of ARDS was categorized according to the Berlin Definition, Berlin Definition altitude-PaO2/FiO2-corrected criteria, and the diagnostic criteria for acute lung injury (ALI)/ARDS at high altitudes in Western China (Zhang criteria). In addition, the differences between the three criteria were compared. Results: Among 1,221 patients, 512 were treated with mechanical ventilation. In addition, 253 met the Berlin Definition, including 49 (19.77%) with mild ARDS, 148 (58.50%) with moderate ARDS, and 56 (22.13%) with severe ARDS. A total of 229 patients met the altitude-PaO2/FiO2-corrected criteria, including 107 with mild ARDS (46.72%), 84 with moderate ARDS (36.68%), and 38 (16.59%) with severe ARDS. Intensive care unit (ICU) mortality increased with the severity of ARDS (mild, 17.76%; moderate, 21.43%; and severe, 47.37%). Twenty-eight-day mortality increased with worsening ARDS (mild 23.36% vs. moderate 44.05% vs. severe 63.16%) (p < 0.001). There were 204 patients who met the Zhang criteria, including 87 (42.65%) with acute lung injury and 117 (57.35%) with ARDS. The area under receiver operating characteristics (AUROCs) of the Berlin Definition, the altitude-P/F-corrected criteria, and the Zhang criteria were 0.6675 (95% CI 0.5866-0.7484), 0.6216 (95% CI 0.5317-0.7116), and 0.6050 (95% CI 0.5084-0.7016), respectively. There were no statistically significant differences between the three diagnostic criteria. Conclusion: For Xining, Qinghai, the altitude-PaO2/FiO2-corrected criteria for ARDS can distinguish the severity of ARDS, but these results need to be confirmed in a larger sample and in multicenter clinical studies. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04199650.

A Systematic Review and Meta- Analysis of Green-Light Laser Vaporization for Superficial Bladder.

PURPOSE: The related research of green-light laser vaporization in the treatment of non-muscle invasive bladder cancer (NMIBC) is limited. This study focused on analyzing the effectiveness and safety of it from the perspective of an extensive literature review. METHODS: A comprehensive search of CNKI, WanFang, VIP, PubMed, Embase, and CENTRAL databases for photoselective vaporization of bladder tumor and transurethral resection of bladder tumor treatment of non-muscle invasive bladder cancer (NMIBC). The search included studies from January 1996 to December 2019. Two reviewers independently screened literature, extracted data, assessed the risk of bias of included studies. RevMan 5.3 software was used for Meta-analysis. RESULTS: A total of 18 RCTs involving 1648 patients met the predefined criteria. Meta-analysis data demonstrated that the PVBT group exhibited a significant advantage over the TURBT group in intraoperative obturator nerve reflex (RR = 0.09, 95% CI [0.04, 0.18], P< 0.001)and bladder perforation (RR = 0.14, 95% CI [0.07, 0.28], P< 0.001) and postoperative 1-year recurrence (RR = 0.52, 95% CI [0.40, 0.67], P< 0.001). The PVBT procedure has advantages over TURBT in the amount of surgical bleeding (MD = -17.27, 95% CI [-24.73, -9.81], P< 0.001) and the length of hospital stay (MD = -2.80, 95% CI [-3.82, -1.87], P< 0.001), bladder irrigation time (MD = -0.95, 95% CI [-1.49, -0.42], P< 0.001), and catheter indwelling time (MD = -2.60, 95% CI [-3.30, -1.90], P< 0.001). There was no difference between the two types of surgery in the incidence of postoperative urethral stricture (RR = 0.53, 95% CI [0.15, 1.83], P = 0.32) and the length of surgery (MD = -2.46, 95% CI [-5.37, 0.46], P = 0.10). CONCLUSION: Our systematic review and meta-analysis suggests that PVBT is better than TURBT as an alternative treatment for patients with NMIBC in safe aspect. However, whether it is equally effective in terms of oncological control remains to be elucidated, and additional high quality RCTs are needed to confirm our findings.

Clinical case report on treatment of Listeria monocytogenes meningoencephalitis: Intrathecal injection.

This article mainly reports the process of clinical diagnosis and treatment of a misdiagnosed Listeria monocytogenes meningoencephalitis. The patient's condition is aggravated because of the ineffective prophase therapy. In the later stage, we were mainly through combined antibiotics and given proper routes of administration, so that patient can recover quickly.