The effect of the concurrent use of Dexmedetomidine (DEX) during the perioperative period on the renal function of patients following craniocerebral interventional surgery.

BACKGROUND: Craniocerebral interventional surgery is a common and essential treatment for cerebrovascular diseases. Despite continuous progress in interventional diagnosis and treatment technology, there is no effective method to alleviate contrast-induced kidney injuries. In this retrospective cohort study, we investigated the effect of the concurrent use of Dexmedetomidine (DEX) during the perioperative period on the renal function of patients following craniocerebral interventional surgery. METHODS: We identified 228 cases of patients underwent craniocerebral interventional surgery from January 2018 to March 2022. Patients who used DEX during general anesthesia were in the DEX group (DEX group) or that did not use dexmedetomidine as the control group (CON group). The markers of kidney injury were recorded before and within 48 h after surgery. RESULTS: Compared with CON group, the urea nitrogen (BUN) of the DEX group decreased significantly on the first day and the second day after surgery (p < 0.05). The serum cystatin-C and the blood urea nitrogen/creatinine ratio (BUN/Cr) was significantly lower than that in CON group on the second day (p < 0.05). The urine output in the DEX group increased significantly, and the mean arterial pressure (MAP) was higher than the CON group (p < 0.01). There was no difference in postoperative complications, ICU stay time and hospitalization time between the two groups. CONCLUSION: The combined use of dexmedetomidine in general anesthesia for craniocerebral interventional surgery can reduce BUN levels within 48 h after surgery, significantly increase intraoperative urine volume, maintain intraoperative circulation stability.

ß-Hydroxybutyrate inhibits histone deacetylase 3 to promote claudin-5 generation and attenuate cardiac microvascular hyperpermeability in diabetes.

AIMS/HYPOTHESIS: Microvascular endothelial hyperpermeability, mainly caused by claudin-5 deficiency, is the initial pathological change that occurs in diabetes-associated cardiovascular disease. The ketone body ß-hydroxybutyrate (BHB) exerts unique beneficial effects on the cardiovascular system, but the involvement of BHB in promoting the generation of claudin-5 to attenuate cardiac microvascular hyperpermeability in diabetes is poorly understood. METHODS: The effects of BHB on cardiac microvascular endothelial hyperpermeability and claudin-5 generation were evaluated in rats with streptozotocin-induced diabetes and in high glucose (HG)-stimulated human cardiac microvascular endothelial cells (HCMECs). To explore the underlying mechanisms, we also measured ß-catenin nuclear translocation, binding of ß-catenin, histone deacetylase (HDAC)1, HDAC3 and p300 to the Claudin-5 (also known as CLDN5) promoter, interaction between HDAC3 and ß-catenin, and histone acetylation in the Claudin-5 promoter. RESULTS: We found that 10 weeks of BHB treatment promoted claudin-5 generation and antagonised cardiac microvascular endothelial hyperpermeability in rat models of diabetes. Meanwhile, BHB promoted claudin-5 generation and inhibited paracellular permeability in HG-stimulated HCMECs. Specifically, BHB (2 mmol/l) inhibited HG-induced HDAC3 from binding to the Claudin-5 promoter, although nuclear translocation or promoter binding of ß-catenin did not change with BHB treatment. In addition, BHB prevented the binding and co-localisation of HDAC3 to ß-catenin in HG-stimulated HCMECs. Furthermore, using mass spectrometry, acetylated H3K14 (H3K14ac) in the Claudin-5 promoter following BHB treatment was identified, regardless of whether cells were stimulated by HG or not. Although reduced levels of acetylated H3K9 in the Claudin-5 promoter were found following HG stimulation, increased H3K14ac was specifically associated with BHB treatment. CONCLUSIONS/INTERPRETATION: BHB inhibited HDAC3 and caused acetylation of H3K14 in the Claudin-5 promoter, thereby promoting claudin-5 generation and antagonising diabetes-associated cardiac microvascular hyperpermeability. Graphical abstract.

Analgesic efficacy and safety of erector spinae plane block in breast cancer surgery: a systematic review and meta-analysis.

BACKGROUND: Surgical resection is considered to be the primary and most effective therapy for breast cancer, postoperative pain is an issue gaining significant attention. In recent years, erector spinae plane block (ESPB) has attracted much attention in postoperative analgesia, but its effectiveness is still controversial. This meta-analysis was implemented to verify the clinical analgesic efficacy and safety of erector spinae plane block in patients undergoing breast cancer surgery. METHODS: We searched PubMed, EMBASE, Web of Science, the Cochrane Library and ClinicalTrials.gov for randomized controlled trials (RCTs) comparing ESPB with general anesthesia (GA) in breast cancer surgery that were published before December 25, 2020. The primary outcome was opioid consumption at the first 24 h after surgery, while secondary outcomes included pain scores at 1, 6,12 and 24 h after surgery, opioid consumption at 1, 6 and 12 h after surgery, intraoperative opioid consumption, number of patients who need for rescue analgesia, and the incidence of postoperative nausea and vomiting (PONV). RESULTS: Eleven randomized controlled trials involving 679 patients met the study inclusion criteria and were included in this study. In comparison to GA group, the ESPB group showed a significant reduction in morphine consumption at the first 24 h after surgery by a mean difference (MD) of - 7.67 mg [95% confidence interval (CI) - 10.35 to - 5.00] (P <  0.01). In addition, the ESPB group showed lower pain scores than the GA group in the four time periods (1, 6, 12 and 24 h after surgery). ESPB group significantly reduce the intraoperative consumption of fentanyl, the need for postoperative rescue analgesia, and the incidence of PONV. CONCLUSIONS: Ultrasound-guided ESPB is an effective approach for reducing morphine consumption and pain intensity within the first 24 h after breast cancer surgery, compared with GA alone.

IL-33 Attenuates Sepsis by Inhibiting IL-17 Receptor Signaling through Upregulation of SOCS3.

BACKGROUND/AIMS: Sepsis is a systemic inflammatory response during infection. There are limited therapeutic options for sepsis patients. Interleukin (IL)-33 has been reported recently with a beneficial effect in mouse sepsis. METHODS: In this study, we initiated a clinical study to measure serum levels of pro-inflammatory cytokines including IL-33 in sepsis patients. Next, we employed cecal ligation and puncture (CLP) to study the role of IL-33 during sepsis. To further dissect the molecular mechanism, we used in vivo knockout models and in vitro knockdown murine embryonic fibroblasts (MEFs) to investigate the cross-talk between IL-33 and IL-17 signaling, and to identify the potential downstream mediators. RESULTS: IL-33 and IL-17 were upregulated in both clinical and experimental sepsis. In CLP, IL-33 (-/-) mice showed higher mortality rate, and IL-33 treatment improved the survival rate. Elevated proinflammatory cytokines in sepsis were related to IL-17 from γδT cells. IL-33 treatment suppressed production of these cytokines by targeting IL-17 signaling both in vivo and in vitro. Finally, IL-33 was shown to inhibit the IL-17 pathway via activating suppressor of cytokine signaling (SOCS)-3. CONCLUSION: Collectively, the results suggest that IL-33 plays a negative regulatory role in sepsis progression by inhibiting IL-17 pathway through activating SOCS3. This finding would inspire a new therapeutic strategy for treating sepsis.

The interplay between mitophagy and mitochondrial ROS in acute lung injury.

Mitochondria orchestrate the production of new mitochondria and the removal of damaged ones to dynamically maintain mitochondrial homeostasis through constant biogenesis and clearance mechanisms. Mitochondrial quality control particularly relies on mitophagy, defined as selective autophagy with mitochondria-targeting specificity. Most ROS are derived from mitochondria, and the physiological concentration of mitochondrial ROS (mtROS) is no longer considered a useless by-product, as it has been proven to participate in immune and autophagy pathway regulation. However, excessive mtROS appears to be a pathogenic factor in several diseases, including acute lung injury (ALI). The interplay between mitophagy and mtROS is complex and closely related to ALI. Here, we review the pathways of mitophagy, the intricate relationship between mitophagy and mtROS, the role of mtROS in the pathogenesis of ALI, and their effects and related progression in ALI induced by different conditions.

Senescent adipocytes and type 2 diabetes - current knowledge and perspective concepts.

Among civilization diseases, the number of individuals suffering from type 2 diabetes (T2DM) is expected to increase to more than a billion in less than 20 years, which is associated with, e.g., populational aging, poor diet, sedentary lifestyle, genetic predispositions, and immunological factors. T2DM affects many organs and is characterized by insulin resistance, high glucose levels, and adipocyte dysfunction, which are related to senescence. Although this type of cellular aging has beneficial biological functions, it can also act unfavorable since senescent adipocytes resist apoptosis, enhance cytokine secretion, downregulate cell identity genes, and acquire the senescence-associated secretory phenotype that renders a more oxidative environment. Opposing T2DM is possible via a wide variety of senotherapies, including senolytics and senomorphics; nevertheless, further research is advised to expand therapeutic possibilities and benefits. Consequences that ought to be deeply researched include secretory phenotype, chronic inflammation, increasing insulin resistance, as well as impairment of adipogenesis and functioning of adipocyte cells. Herein, despite reviewing T2DM and fat tissue senescence, we summarized the latest adipocyte-related anti-diabetes solutions and suggested further research directions.

Efficacy of Perioperative Intercostal Analgesia via a Multimodal Analgesic Regimen for Chronic Post-Thoracotomy Pain During Postoperative Follow-Up: A Big-Data, Intelligence Platform-Based Analysis.

BACKGROUND: Chronic post-thoracotomy pain is still an obstacle for lung-cancer patients even after less invasive surgical procedures. It is unclear whether intercostal analgesia is as useful in the prevention of postoperative chronic pain as it is for acute pain for video-assisted thoracoscopic surgery (VATS). The purpose of this study was to evaluate the efficacy of perioperative intercostal analgesia for chronic pain via a multimodal analgesic regimen for VATS during 6 months of postoperative follow-up. METHODS: We identified 837 cases of VATS from August 2016 to August 2018. Patients were treated by perioperative intercostal analgesia with 0.75% ropivacaine 50 mg through the intercostal catheter every 8 hours until chest tube extubation (INA group) or conventional analgesia with preoperative 0.75% ropivacaine 50 mg at incision once (CON group). Numerical rating scale (NRS) and neuropathic pain were evaluated in 6 months of post-surgery follow-up. Postoperative adverse effects were recorded. RESULTS: In total, there were 419 patients in INA group and 418 patients in CON group. Scores of NRS with motion was lower in INA group at 3 postoperative days (P = 0.032). Occurrence of chronic pain was 28.4% in INA group and 32.8% in CON group at 6 postoperative months, 10.6% of patients experienced increasing pain from 3 to 6 months. Occurrence of considerable neuropathic pain (ID pain score ≥ 2) was 2.1% in INA group and 3.1% in CON group at 6 postoperative months. No differences were found between the two groups. Occurrence of numbness was lower in INA group (6.7% vs 10.5%, P = 0.031), and other pain symptoms did not differ between the groups. The incidence of dizziness, nausea, vomiting and atelectasis was not different between the two groups. CONCLUSION: In a multimodal analgesic regimen of VATS, perioperative intercostal analgesia with 0.75% ropivacaine infusion 50 mg three times in a day does not have an obvious effect on chronic post-thoracotomy pain.

Up-regulation of MMP-2 by histone H3K9 ß-hydroxybutyrylation to antagonize glomerulosclerosis in diabetic rat.

AIMS: Besides energy supply, ß-hydroxybutyrate (BHB) acts as a bioactive molecule to play multiple protective roles, even in diabetes and its complications. The aim of this study was to investigate the antagonizing effects of BHB against diabetic glomerulosclerosis and the underlying mechanism. METHODS: Male Sprague-Dawley rats were intraperitoneally injected with streptozotocin to induce diabetes and then treated with different concentrations of ß-hydroxybutyrate. After 10 weeks, body weight, blood glucose, serum creatinine and 24-h urine protein were examined. Glomerular morphological changes and the contents of collagen type IV (COL IV) were evaluated. Then, transforming growth factor (TGF)-ß/Smad3 contents and matrix metalloproteinase-2 (MMP-2) generation were detected. Moreover, the total contents of trans-activating histone H3K9 ß-hydroxybutyrylation (H3K9bhb) and the contents of H3K9bhb in the Mmp-2 promoter were measured. RESULTS: It was firstly confirmed that BHB treatments reduced renal biochemical indicators and attenuated glomerular morphological changes of the diabetic rats, with COL IV content decreased in a concentration-dependent manner. Then, BHB treatments were found to up-regulate renal MMP-2 generation of the diabetic rats significantly, while not affecting the increased TGF-ß/Smad3 contents. Furthermore, the contents of H3K9bhb in the Mmp-2 promoter were elevated significantly for the middle and high concentrations of BHB treatments, up-regulating MMP-2 generation. CONCLUSION: BHB treatments could up-regulate MMP-2 generation via causing elevated H3K9bhb in its promoter to antagonize glomerulosclerosis in the diabetic rats.

The efficacy of pregabalin for the management of acute and chronic postoperative pain in thoracotomy: a meta-analysis with trial sequential analysis of randomized-controlled trials.

PURPOSE: Pregabalin is commonly used as an analgesic for neuropathic pain. But pregabalin as an adjunct to a multimodal analgesic regimen - although standard clinical protocol in some settings - has remained controversial. This meta-analysis was conducted to identify the efficacy of pregabalin for management of postoperative pain in thoracotomy. MATERIALS AND METHODS: Pubmed, Embase, Cochrane, Web of Science, Springer, and Clinical Trial Register database were searched for randomized controlled trials (RCTs) of pregabalin in preventing postoperative pain in thoracotomy. Review Manager 5.3 and STATA 12.0 were selected to conduct the meta-analysis. Trial sequential analysis was used to control random errors and calculate the required information size. RESULTS: Nine RCTs with 684 patients were included in our meta-analysis. Outcomes favoring pregabalin included less pain on a 0-10 scale on 1 day [mean difference (MD): -0.87; 95% CI: -1.55 to -0.19; P=0.01], 3 days (MD: -1.55; 95% CI: -1.93 to -1.18; P<0.00001), 1 month (MD: -1.58; 95% CI: -2.75 to -0.42; P=0.008), 3 months (MD: -1.69; 95% CI: -2.71 to -0.66; P=0.001) postoperatively, and less incidence of neuropathic pain (OR: 0.20; 95% CI: 0.05-0.91; P=0.04), less mean morphine consumption (MD: -5.03; 95% CI: -8.06 to -1.99; P=0.001), but more dizziness (OR: 3.33; 95% CI: 1.36-8.17; P=0.009), more drowsiness (OR: 8.61; 95% CI: 2.23-33.20; P=0.002), and less constipation (OR: 0.23; 95% CI: 0.09-0.59; P=0.002). There was no statistical differences in pain score on 7 days (MD:-0.77; 95% CI: -2.38 to 0.84; P=0.35), nausea (OR: 0.73; 95% CI: 0.42-1.26; P=0.26), and vomiting (OR: 0.83; 95% CI: 0.36-1.90; P=0.65). CONCLUSION: Pregabalin can prevent postoperative pain in thoracotomy and decrease incidence of neuropathic pain and morphine consumption. Pregabalin may be a valuable asset in management of acute and persistent postoperative pain in thoracotomy.

Targeted induction of bone marrow mesenchymal stem cells to have effectiveness on diabetic pancreatic restoration.

Although bone marrow-derived mesenchymal stem cells (BMSCs) have been reported to be effective for the attenuation of diabetes, they have limitations. Whether BMSCs can be target-induced by pancreatic stem cells (PSCs) to have effectiveness for the restoration of diabetic islet injury was unknown. In this study, based on their successful isolation and cultivation, BMSCs were co-cultured with PSCs. The pancreatic stem cells markers, Nestin and Neurogenin3 in co-cultured BMSCs were detected to evaluate the target-induction effects. After the diabetic rats were intravenously injected with the target-induced BMSCs, general indicators and islet morphology were detected. The islet insulin generation, and serum insulin and C-peptide contents were measured. It was found that after co-culture, the mRNA expressions, protein contents and distributions of Nestin and Neurogenin3, were dramatically high in BMSCs, indicating that they were successfully target-induced to pancreatic stem-like cells. Furthermore, the target-induced BMSCs had beneficial effects on serum glycated albumin levels and glycogen contents as well as islet morphology of the diabetic rats. Besides elevation of islet insulin generation, the target-induced BMSCs had significant effect on serum insulin and C-peptide contents. In conclusion, BMSCs could be target-induced by PSCs to have effectiveness on the pancreatic restoration of diabetic rats.

Impact of warming blood transfusion and infusion toward cerebral oxygen metabolism and cognitive recovery in the perioperative period of elderly knee replacement.

OBJECTIVE: This study aims to observe the impact of the temperature of blood transfusion and infusion toward the perioperative cerebral oxygen metabolism and the postoperative cognitive recovery. METHODS: Eighty patients of knee replacement under epidural and general anesthesia were randomly divided into warming blood transfusion and infusion (WBI) group (n = 40) and control group (n = 40). The changes of nasopharyngeal temperature, middle cerebral artery blood flow, CERO2, and SjVO2 of the two groups were recorded at each time point for the assessment of the postoperative overall quality of recovery and cognitive recovery situation. RESULTS: The nasopharyngeal temperatures of the two groups at different time points after transfusion were significantly lower than that at T1, and there was a significant difference between the two groups (P < 0.05). The CERO2 values of the two groups at T3 were significantly higher than at T1, while the SjVO2 values were significantly decreased (P < 0.01). CONCLUSION: The WBI can significantly reduce the occurrence of the perioperative hypothermia, while it has no significant effect toward cerebral oxygen metabolism, postoperative overall recovery, and recovery of cognitive function.