Nanoceria-Mediated Cyclosporin A Delivery for Dry Eye Disease Management through Modulating Immune-Epithelial Crosstalk.

Dry eye disease (DED) affects a substantial worldwide population with increasing frequency. Current single-targeting DED management is severely hindered by the existence of an oxidative stress-inflammation vicious cycle and complicated intercellular crosstalk within the ocular microenvironment. Here, a nanozyme-based eye drop, namely nanoceria loading cyclosporin A (Cs@P/CeO2), is developed, which possesses long-term antioxidative and anti-inflammatory capacities due to its regenerative antioxidative activity and sustained release of cyclosporin A (CsA). In vitro studies showed that the dual-functional Cs@P/CeO2 not only inhibits cellular reactive oxygen species production, sequentially maintaining mitochondrial integrity, but also downregulates inflammatory processes and repolarizes macrophages. Moreover, using flow cytometric and single-cell sequencing data, the in vivo therapeutic effect of Cs@P/CeO2 was systemically demonstrated, which rebalances the immune-epithelial communication in the corneal microenvironment with less inflammatory macrophage polarization, restrained oxidative stress, and enhanced epithelium regeneration. Collectively, our data proved that the antioxidative and anti-inflammatory Cs@P/CeO2 may provide therapeutic insights into DED management.

Biological functions and clinical significance of tRNA-derived small fragment (tsRNA) in tumors: Current state and future perspectives.

A new class of noncoding RNAs, tsRNAs are not only abundant in humans but also have high tissue specificity. Recently, an increasing number of studies have explored the correlations between tsRNAs and tumors, showing that tsRNAs can affect biological behaviors of tumor cells, such as proliferation, apoptosis and metastasis, by modulating protein translation, RNA transcription or posttranscriptional regulation. In addition, tsRNAs are widely distributed and stably expressed, which endows them with broad application prospects in diagnosing and predicting the prognosis of tumors, and they are expected to become new biomarkers. However, notably, the current research on tsRNAs still faces problems that need to be solved. In this review, we describe the characteristics of tsRNAs as well as their unique features and functions in tumors. Moreover, we also discuss the potential opportunities and challenges in clinical applications and research of tsRNAs.

Cholesterol metabolism: physiological regulation and diseases.

Cholesterol homeostasis is crucial for cellular and systemic function. The disorder of cholesterol metabolism not only accelerates the onset of cardiovascular disease (CVD) but is also the fundamental cause of other ailments. The regulation of cholesterol metabolism in the human is an extremely complex process. Due to the dynamic balance between cholesterol synthesis, intake, efflux and storage, cholesterol metabolism generally remains secure. Disruption of any of these links is likely to have adverse effects on the body. At present, increasing evidence suggests that abnormal cholesterol metabolism is closely related to various systemic diseases. However, the exact mechanism by which cholesterol metabolism contributes to disease pathogenesis remains unclear, and there are still unknown factors. In this review, we outline the metabolic process of cholesterol in the human body, especially reverse cholesterol transport (RCT). Then, we discuss separately the impact of abnormal cholesterol metabolism on common diseases and potential therapeutic targets for each disease, including CVD, tumors, neurological diseases, and immune system diseases. At the end of this review, we focus on the effect of cholesterol metabolism on eye diseases. In short, we hope to provide more new ideas for the pathogenesis and treatment of diseases from the perspective of cholesterol.

Peptidase inhibitor 16 promotes proliferation of pancreatic ductal adenocarcinoma cells through OASL signaling.

Pancreatic ductal adenocarcinoma (PDAC) is a highly invasive cancer with a poor prognosis and a 5-year survival rate of less than 11%. As a member of the CAP superfamily of proteins, the role of peptidase inhibitor 16 (Pi16) in tumor progression is still unclear. Immunohistochemistry and quantitative RT-PCR methods were used to detect the expression levels of Pi16 protein and mRNA in PDAC patients. CRISPR/Cas9 technology was used to knock out the expression of Pi16 in PDAC cell lines. In vivo and in vitro experiments were used to verify the effect of Pi16 on PDAC proliferation ability. By RNA sequencing, we found that oligoadenylate synthetase L (OASL) can serve as a potential downstream target of Pi16. The expression of Pi16 was higher in PDAC tissues than in matched adjacent tissues. High expression of Pi16 was associated with PDAC progression and poor prognosis. Overexpression of Pi16 could promote the proliferation of PDAC cells in vitro and in vivo. Bioinformatics analysis and coimmunoprecipitation assays showed that Pi16 could bind to OASL. Moreover, the functional recovery test confirmed that Pi16 could promote the proliferation of PDAC via OASL. Our present study demonstrates that Pi16 might participate in the occurrence and development of PDAC by regulating cell proliferation by binding to OASL, indicating that Pi16 might be a promising novel therapeutic target for PDAC.

Ghost in the right atrium: A case report on successful identification of residual fibrous tissue.

The term "ghost" refers to residual fibrous tissue that remains within the cardiovascular system following the removal of implanted device leads. In this case, a 75-year-old male underwent a transvenous lead extraction procedure prompted by an infection. After the procedure, transesophageal echocardiography (TEE) revealed a stable "ghost" in the right atrium. Figures and videos dynamically depicted the ghost's morphology, clearly showing that one end of this spectral entity was firmly attached to the atrial wall, while the other end displayed unrestrained mobility within the bloodstream. After undergoing a thorough evaluation that confirmed the benign nature of the "ghost", there was evidently no need for medical intervention. In summary, the article portrayed a rare yet intriguing "ghost" observed during the perioperative period. Furthermore, this study emphasizes the crucial significance of accurately distinguishing between these "ghosts" and genuinely pathological structures. Such differentiation holds immense importance in preventing unnecessary medical interventions.

Assessment of Total Ropivacaine Concentration in Blood after Bilateral Pecto-Intercostal Fascial Block Combined with Rectus Sheath Block in Cardiac Surgery Patients.

OBJECTIVES: Pecto-intercostal fascial block (PIFB) and rectus sheath block (RSB) have been combined to offer better analgesia for cardiac surgery patients, but safety of the analgesic protocol with a large volume of ropivacaine is uncertain. METHODS: This is a prospective observational study at Peking University People's Hospital to investigate the pharmacokinetic profile of ropivacaine after combined regional blocks. Patients undergoing elective cardiac surgery by a median sternotomy were enrolled to receive bilateral PIFB and RSB with 70 mL 0.3% ropivacaine (total dose 210 mg). Blood was sampled at 5, 10, 15, 30, 60, 90 and 120 mins after blocks. Total blood concentration of ropivacaine for patients were measured. RESULTS: Ten patients were enrolled and analyzed. The peak total ropivacaine concentration varied from 0.67 to 2.42 µg/mL. Time to reach the peak values mainly located between 10 and 30 mins after the performance. No patients had ropivacaine concentration values above toxic threshold (4.3 µg/mL), and there were no systemic toxicity symptoms during the perioperative period. CONCLUSIONS: PIFB combined with RSB in a general injection of 70 mL 0.3% ropivacaine does not give rise to toxic levels, and it is an effective and safe analgesic protocol for cardiac surgery patients.

Left atrial appendage thrombus in an elderly patient with atrial fibrillation during non-cardiac surgery- a case report.

BACKGROUND: Perioperative newly developed left atrial appendage (LAA) thrombus is a rare but extremely challenging event for anesthesia management. It's important to identify and diagnose thrombosis in high-risk populations promptly. CASE PRESENTATION: In the case of an elderly patient with atrial fibrillation undergoing non-cardiac surgery, we recorded the findings before and after thrombosis during the operation using transesophageal echocardiography (TEE). Through timely detection of the thrombus and proactive management, a satisfactory therapeutic effect was ultimately achieved. CONCLUSIONS: Clinicians should be aware of the potential risk of LAA clot formation during surgery, even if it was not detected preoperatively. And TEE is valuable for monitoring newly developed perioperative thrombosis.

Optimal Duration of High-Fidelity Simulator Training for Bronchoscope-Guided Intubation: A Noninferiority Randomized Trial.

INTRODUCTION: The optimal simulator training duration for flexible optical bronchoscopic (FOB) intubation is unknown. This study aimed to determine whether a learning curve-based training modality was noninferior to a fixed training time modality in terms of clinical FOB intubation time. METHODS: This multicenter, randomized, noninferiority study was conducted from May to August 2022. Anesthesiology residents or interns were enrolled. Eligible participants were randomized in a 1:1 ratio to receive new learning curve-based simulator training (individualized training time based on performance, group New) or reference fixed training time simulator training (1 hour, group Reference). The primary outcome was the time to complete FOB intubation in patients, which was defined as the time from the introduction of the FOB into the mouth until the first capnography visualization. The margin for detecting clinical significance was defined as 10 seconds. RESULTS: A total of 32 participants were included in the analysis (16 in each group). All trainees successfully intubated the patients. The mean intubation time (95% confidence interval [CI]) was 81.9 (65.7-98.1) seconds in group New and 97.0 (77.4-116.6) seconds in group Reference. The upper bound of the 1-sided 97.5% CI for the mean difference of clinical intubation time between groups was 9.3 seconds. Noninferiority was claimed. The mean duration of the training in group New was 28.4 (95% CI, 23.5-33.4) minutes. The total number of training procedures on simulators in group New was significantly less than that in group Reference (P < 0.01). CONCLUSIONS: The clinical FOB intubation time in group New was noninferior to that in group Reference.

Preoperative resting-state microstate as a marker for chronic pain after breast cancer surgery.

INTRODUCTION: Chronic postoperative pain poses challenges, emphasizing the importance of accurately predicting pain in advance. Generally, pain perception is associated with the temporal dynamics of the brain, which can be represented by microstates. Specifically, microstates are transient and patterned brain topographies formed by temporally overlapping and spatially synchronized oscillatory activities. Consequently, by characterizing brain activity, microstates offer valuable insights into pain perception. METHODS: In this prospective study, 66 female patients undergoing breast cancer surgery were included. Their preoperative resting-state electroencephalography (EEG) was recorded. Preoperative resting-state EEG was recorded and four specific brain microstates (labeled as A, B, C, and D) were extracted. Temporal characteristics were then analyzed from these microstates. Patients were classified into two groups based on their Numerical Rating Scale (NRS) scores at three months postoperatively. Those with NRS scores ranging from 4 to 10 were classified as the high pain group, while patients with NRS ranging from 0 to 3 were classified as the lowpain group. Statistical analyses were performed to compare the microstate characteristics between these two groups. RESULTS: Twenty-one patients (32%) were classified as the high pain group and forty-five (68%) as the low-pain group. The occurrence and coverage of microstate C were significantly higher in the high pain group. Additionally, there were significant differences in the microstates transitions between the two groups. Furthermore, the study revealed a positive correlation between the coverage of microstate C and the NRS. CONCLUSIONS: Preoperative resting-state microstate features have shown correlations with postoperative pain. This study presents a novel and advanced perspective on the potential of microstates as a marker for postoperative pain.

Intraoperative Fraction of Inspired Oxygen and Lung Injury in Coronary Artery Bypass Grafting: Study Protocol for a Randomised Controlled Trial.

OBJECTIVE: Postoperative pulmonary complications are a series of disorders that can contribute to respiratory distress and prolonged mechanical ventilation postoperatively. We hypothesise that a liberal oxygenation strategy during cardiac surgery leads to a higher incidence of postoperative pulmonary complications than a restrictive oxygenation strategy. METHODS: This study is a prospective, observer-blinded, centrally randomised and controlled, international multicentre clinical trial. RESULTS: After obtaining a written informed consent, 200 adult patients undergoing coronary artery bypass grafting will be enrolled and randomised to receive either restrictive or liberal oxygenation perioperatively. The liberal oxygenation group will receive 1.0 fraction of inspired oxygen throughout the intraoperative period, including during cardiopulmonary bypass. The restrictive oxygenation group will receive the lowest fraction of inspired oxygen required to maintain arterial partial pressure of oxygen between 100 and 150 mmHg during cardiopulmonary bypass and a pulse oximetry reading of 95% or greater intraoperatively, but no less than 0.3 and not higher than 0.80 (other than induction and when the oxygenation goals cannot be reached). When patients are transferred to the intensive care unit, all patients will receive an initial fraction of inspired oxygen of 0.5, and then fraction of inspired oxygen will be titrated to maintain a pulse oximetry reading of 95% or greater until extubation. The lowest postoperative arterial partial pressure of oxygen/fraction of inspired oxygen within 48 hours of intensive care unit admission will be the primary outcome. Postoperative pulmonary complications, length of mechanical ventilation, intensive care unit stay, hospital stay, and 7-day mortality after cardiac surgery will be analysed as secondary outcomes. CONCLUSION: This is one of the first randomised controlled observer-blinded trials that prospectively evaluates the influence of higher inspired oxygen fractions on early postoperative respiratory and oxygenation outcomes in cardiac surgery patients using cardiopulmonary bypass.

Evaluation of fluid responsiveness with dynamic superior vena cava collapsibility index in mechanically ventilated patients.

BACKGROUND: This study aimed to evaluate the predictive accuracy of the superior vena cava collapsibility index measured by transesophageal echocardiography and compare the index with stroke volume variation measured by FloTrac™/Vigileo™ in mechanically ventilated patients. METHODS: In the prospective study, a total of 60 patients were enrolled for elective general surgery under mechanical ventilation, where all patients received 10 ml/kg of Ringer's lactate. Five kinds of related data were recorded before and after the fluid challenge, including the superior vena cava collapsibility index (SVC-CI), the ratio of E/e', cardiac index (CI), stroke volume variation (SVV), and central venous pressure (CVP). Based on the collected data after the fluid challenge, we classified the patients as responders (FR group) if their CI increased by at least 15% and the rest were non-responders (NR). RESULTS: Twenty-five of 52 (48%) of the patients were responders, and 27 were non-responders (52%). The SVC-CI was higher in the responders (41.90 ± 11.48 vs 28.92 ± 9.05%, P < 0.01). SVC-CI was significantly correlated with △CI FloTrac (r = 0.568, P < 0.01). The area under the ROC curve (AUROC) of SVC-CI was 0.838 (95% CI 0.728 ~ 0.947, P < 0.01) with the optimal cutoff value of 39.4% (sensitivity 64%, specificity 92.6%). And there was no significant difference in E/e' between the two groups (P > 0.05). The best cutoff value for SVV was 12.5% (sensitivity 40%, specificity 89%) with the AUROC of 0.68 (95% CI 0.53 ~ 0.826, P < 0.05). CONCLUSIONS: The SVC-CI and SVV can predict fluid responsiveness effectively in mechanically ventilated patients. And SVC-CI is superior in predicting fluid responsiveness compared with SVV. The E/e' ratio and CVP cannot predict FR effectively. TRIAL REGISTRATION: Chinese clinical trial registry (ChiCTR2000034940).

Effect of pecto-intercostal fascial block on extubation time in patients undergoing cardiac surgery: A randomized controlled trial.

Objectives: Epidural and paravertebral block reduce the extubation time in patients undergoing surgery under general anesthesia but are relatively contraindicated in heparinized patients due to the potential risk of hematoma. The Pecto-intercostal fascial block (PIFB) is an alternative in such patients. Methods: This is a single-center randomized controlled trial. Patients scheduled for elective open cardiac surgery were randomized at a 1:1 ratio to receive PIFB (30 ml 0.3% ropivacaine plus 2.5 mg dexamethasone on each side) or saline (30 ml normal saline on each side) after induction of general anesthesia. The primary outcome was extubation time after surgery. Secondary outcomes included opioid consumption during surgery, postoperative pain scores, adverse events related to opioids, and length of stay in the hospital. Results: A total of 50 patients (mean age: 61.8 years; 34 men) were randomized (25 in each group). The surgeries included sole coronary artery bypass grafting in 38 patients, sole valve surgery in three patients, and both procedures in the remaining nine patients. Cardiopulmonary bypass was used in 20 (40%) patients. The time to extubation was 9.4 ± 4.1 h in the PIFB group vs. 12.1 ± 4.6 h in the control group (p = 0.031). Opioid (sufentanil) consumption during surgery was 153.2 ± 48.3 and 199.4 ± 51.7 µg, respectively (p = 0.002). In comparison to the control group, the PIFB group had a lower pain score while coughing (1.45 ± 1.43 vs. 3.00 ± 1.71, p = 0.021) and a similar pain score at rest at 12 h after surgery. The two groups did not differ in the rate of adverse events. Conclusions: PIFB decreased the time to extubation in patients undergoing cardiac surgery. Trial Registration: This trial is registered at the Chinese Clinical Trial Registry (ChiCTR2100052743) on November 4, 2021.

Effects of pecto-intercostal fascial block combined with rectus sheath block for postoperative pain management after cardiac surgery: a randomized controlled trial.

BACKGROUND: Pecto-intercostal fascial block (PIFB) provides analgesia for cardiac median sternotomy, but many patients complain of severe drainage pain that cannot be covered by PIFB. Rectus sheath block (RSB) has been attempted to solve this problem, but whether PIFB combined with RSB can achieve better analgesia is uncertain. METHODS: This was a single-center randomized controlled trial at Peking University People's Hospital from September 22, 2022 to December 21, 2022. Patients undergoing elective cardiac surgery with a median sternotomy were randomized at a 1:1 ratio to receive either bilateral PIFB and RSB (PIFB + RSB group) or PIFB (PIFB group). The primary outcome was intravenous opioid consumption within 24 h after surgery. Secondary outcomes included opioid consumption within 48 h, postoperative pain scores, time to extubation, and length of stay in the hospital. Interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α before and the first 24 h after surgery were measured. RESULTS: A total of 54 patients were analyzed (27 in each group). Intravenous opioid consumption within 24 h after surgery was 2.33 ± 1.77 mg in the PIFB + RSB group vs 3.81 ± 2.24 mg in the PIFB group (p = 0.010). Opioid consumption within 48 h after surgery was also reduced in the PIFB + RSB group (4.71 ± 2.71 mg vs 7.25 ± 3.76 mg, p = 0.006). There was no significant difference in pain scores, time to extubation, length of stay in hospital, or the levels of IL-6, IL-10 and TNF-α between the two groups. CONCLUSIONS: The combination of PIFB and RSB reduced postoperative intravenous opioid consumption until 48 h after cardiac surgery. TRIAL REGISTRATION: This trial is registered at the Chinese Clinical Trial Registry ( www.chictr.org.cn , ChiCTR2200062017) on 19/07/2022.

The clinical role of transesophageal echocardiography during transvenous lead extraction.

BACKGROUND: Transesophageal echocardiography (TEE) is commonly used during cardiothoracic procedures. TEE has also become standard during transvenous lead extraction (TLE) procedures, but its effect and role have not been optimally defined. The goal of this study is to identify how TEE was used during TLE at our institute and review its utility. METHODS: We retrospectively reviewed high-risk patients undergoing TLE, for whom more complications during extraction procedures, from June 2012 to September 2020. The patients were divided into TEE group and non-TEE group according to real-time TEE monitoring. We compared the rate of procedural success, complications between two groups and concluded the clinical utility of TEE during TLE. RESULTS: A total of 195 patients were included (105 in TEE group vs 90 in non-TEE group), the rate of procedure success (97.8% vs 96.5%, p = 0.41) and complications during extraction (8.6% vs 12.2%, p = 0.40, major complication 5.7% vs 12.2%, p = 0.11, minor complication 2.9% vs 0%, p = 0.30) were comparable. In TEE group, 12 patients (11.4%) received following benefits: altering surgical plans, guiding subsequent therapy strategies, and rapidly diagnosing complications, moreover no complications occurred from TEE. CONCLUSIONS: This study demonstrates that real-time monitoring by TEE cannot change the rate of procedural success and complication during TLE; however, TEE provides valuable information to instruct clinical therapy and improves the safety of TLE.

Perioperative Risk Assessment for Surgery of Consecutive Cases with Ventricular Septal Rupture: Seeking A Novel and Comprehensive Method.

BACKGROUND: Ventricular septal rupture (VSR) is a rare but lethal complication occurring after acute myocardial infarction. The aim of our study was to review the single-center experience of surgery for VSR and seek a comprehensive evaluation process for early mortality. METHODS: Patients undergoing surgical repair for postinfarction VSR in our institution retrospectively were evaluated from Jan. 2006 to Dec. 2019. The endpoint of the study was mortality within 30 days after VSR surgery, which was divided into survivors and nonsurvivors. The calibration and discrimination of two risk evaluation systems (European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) and the Society of Thoracic Surgeons (STS) risk score) in total were compared by Hosmer-Lemeshow, and the area under the receiver operating characteristic curve (AUC). Risk factors in subsets were assessed by logistic regression analysis. RESULTS: Twenty-three patients undergoing surgery for VSR repair were reviewed, and the early mortality after surgery was 34.8% (N = 8). The expected mortality predicted by EuroSCORE II was 24.3%, and that of the STS score was 12.2%. Both the EuroSCORE II and STS risk evaluation systems showed positive calibration in predicting mortality (H-L: P = 0.117 and P = 0.346, respectively) but poor discriminative power (AUC=0.633 and 0.575). Significant predictors determined by univariate analysis were concomitant coronary artery bypass grafting (CABG) (P = 0.035) and postoperative continuous renal replacement therapy (CRRT) (P = 0.008). CONCLUSION: Early mortality of VSR after surgery remains high, and the evaluation process is complicated. The performances of the two risk evaluation systems were not optimal, but EuroSCORE II was more accurate than STS. Patients with lower preoperation EuroSCORE II, concomitant CABG during repair, and no need for CRRT after surgery may have a better early survival rate.

Anesthetic management of bilateral pheochromocytoma resection in Von Hippel-Lindau syndrome: A case report.

BACKGROUND: Von Hippel-Lindau disease (also known as VHL syndrome), is an autosomal dominant inherited disease. We describe a sporadic case of VHL syndrome where bilateral pheochromocytomas were unexpectedly identified. The patient underwent selective laparoscopic resections of the pheochromocytomas, and the anesthetic management during surgery was complex and challenging. CASE SUMMARY: A 22-year-old man presented to our hospital to seek medical advice for infertility without any other complaints. The results of computed tomography and catecholamine levels in blood and urine demonstrated adrenal gland masses which were diagnosed as pheochromocytomas. Further examination confirmed that the patient also had VHL syndrome. After thorough preparation, the patient underwent selective laparoscopic resection of the pheochromocytomas and was discharged 10 d after surgery. We describe the process of perioperative anesthesia management in this patient undergoing pheochromocytoma resection. CONCLUSION: This case summaries specific clinical traits and considerations in perioperative anesthesia management for VHL syndrome patients undergoing bilateral pheochromocytoma resection.