Analgesic effect of the ultrasound-guided thoracolumbar paravertebral block in patients undergoing robot-assisted laparoscopic nephrectomy: a randomized controlled trial.

BACKGROUND: Paravertebral block has similar effect as epidural anesthesia, and has good somatic and visceral analgesic effect. Paravertebral block is widely used in thoracic surgery, but rarely used in abdominal surgery. AIMS: This study aimed to evaluate the analgesic effect of thoracolumbar paravertebral block in patients undergoing robot-assisted laparoscopic nephrectomy. METHODS: One hundred patients undergoing elective robot-assisted laparoscopic nephrectomy were included in this study. Based on whether the thoracolumbar paravertebral block was performed, the patients were randomly divided into the thoracolumbar paravertebral block combined with general anesthesia group (TL-PVB group) and simple general anesthesia group (NO-PVB group). Oxycodone was administered for patient-controlled intravenous analgesia (PCIA). The primary outcomes included the amount of remifentanil used during surgery, the amount of oxycodone used in 24 and 48 h after surgery. Secondary outcomes included the changes of heart rate (HR) and mean arterial pressure (MAP), time for the first analgesia administration, visual analog score (VAS) of pain during rest and movement, and time of postoperative recovery. RESULTS: Compared to the NO-PVB group, the amount of remifentanil used during surgery in patients with TL-PVB group was significantly reduced (1.78 ± 0.37 mg vs. 3.09 ± 0.48 mg, p < 0.001), the amount of oxycodone used 24 h after surgery was significantly reduced (8.70 ± 1.70 mg vs. 13.79 ± 2.74 mg, p < 0.001), and the amount of oxycodone used 48 h after surgery was remarkably reduced (21.83 ± 4.28 mg vs. 27.27 ± 4.76 mg, p < 0.001). There were significant differences in the changes of HR and MAP between the two groups (p < 0.001). The first analgesic requirement time of TL-PVB group was significantly longer than that of NO-PVB group (468.56 ± 169.60 min vs. 113.48 ± 37.26 min, p < 0.001). The postoperative VAS during rest and movement of TL-PVB group were significantly lower than that of NO-PVB group (p < 0.01). Compared with NO-PVB group, patients in TL-PVB group needed shorter time to awaken from anesthesia, leave the operating room, anal exhaust, get out of bed, and had shorter length of postoperative hospital stay (p < 0.001). The incidence of postoperative adverse reactions were lower in the TL-PVB group than that in the NO-PVB group (p < 0.05). CONCLUSIONS: Ultrasound-guided thoracolumbar paravertebral block significantly reduces intraoperative and postoperative opioid consumption, and provides better analgesia in patients undergoing robot-assisted laparoscopic nephrectomy, which is a recommendable combined anesthesia technique. TRIAL REGISTRATION: ChiCTR2200061326, 21/06/2022.

Association between admission prothrombin time activity and hospital readmission in heart failure: A retrospective study.

BACKGROUND: Coagulopathy is a common complication of heart failure (HF), but the prognostic significance of coagulation abnormalities for HF is still poorly understood. This investigation sought to elucidate the association between admission prothrombin time activity (PTA) and short-term readmission in HF. METHODS: In this retrospective study, we extracted data from a publicly accessible database for hospitalized HF patients in China. The admission laboratory findings were screened by the least absolute shrinkage and selection operator (LASSO) regression. Afterward, the study population was stratified according to the admission PTA level. In univariate and multivariate analysis, we employed logistics regression model to evaluate the association of admission PTA level with short-term readmission. Subgroup analysis was preformed to examine the interaction effect between admission PTA level and covariates, including age, sex, and systolic blood pressure (SBP). RESULTS: A total of 1505 HF patients were included, of whom 58.7% were female and 35.6% were between 70 and 79 y. In LASSO procedure, admission PTA level was included in optimized models for short-term readmission, and readmitted patients tended to have a lower admission PTA level. Multivariate analysis suggested that the low admission PTA level (admission PTA ≤ 62.3%) was associated with increased risk of 90-day readmission (odds ratio 1.63 [95% CI, 1.09 to 2.46]; P = 0.02) and 180-day readmission (odds ratio 1.65 [95% CI, 1.18 to 2.33]; P = 0.01) compared with patients with the highest admission PTA level (admission PTA ≥ 76.8%) after full adjustment. Moreover, no significant interaction effect was observed in the subgroup analysis, except for admission SBP. CONCLUSION: Low admission PTA level is associated with an increased risk of 90-day and 180-day hospital readmission in patients with HF.

Neuregulin 4 Attenuates Osteoarthritis Progression by Inhibiting Inflammation and Apoptosis of Chondrocytes in Mice.

Osteoarthritis (OA) is characterized by chondrocyte apoptosis and increased degradation of type II collagen. Inflammation is one of the major risk factors involved in the pathophysiology of OA. Neuregulin 4 (Nrg4) plays a protective role in a variety of low-level inflammatory diseases, such as non-alcoholic fatty liver disease, inflammatory bowel disease, or type 2 diabetes mellitus. Here we found that (1) Nrg4 deficiency aggravated the destruction and inflammation of articular cartilage and the apoptosis of chondrocytes in vivo. (2) Nrg4 restoration reversed these changes in vivo. (3) Murine recombinant Nrg4 (rNrg4) suppressed inflammation and apoptosis of chondrocytes and decreased the degradation of extracellular matrix in vitro. (4) Mechanistically, the mitogen-activated protein kinase/c-jun N-terminal kinase (MAPK/JNK) signaling pathway may be involved in the regulation of Nrg4 in the pathophysiology of OA. Therefore, we concluded that Nrg4 alleviated the progression of OA by inhibiting the inflammation, protecting against apoptosis of chondrocyte, and decreasing the degradation of extracellular matrix in a manner involving MAPK/JNK signaling.

Knockdown of USP9X reverses cisplatin resistance by decreasing ß-catenin expression in nasopharyngeal carcinoma cells.

In various cancers, abnormal USP9X expression is involved in tumorigenesis, progression, apoptosis, and metastasis. However, the relationship between USP9X abnormal expression and cisplatin resistance in nasopharyngeal carcinoma (NPC) cells remains unclear. Using qRT-PCR and western blot, we detected the expressions of USP9X and ß-catenin in NPC cells. The effects of USP9X on cisplatin resistance, proliferation, apoptosis, and metastasis were examined by CCK-8 assay, flow cytometry, wound-healing assay, and Transwell chamber assay. Co-IP assay, qRT-PCR, and western blot were performed to explore the detailed molecular mechanism of USP9X-ß-catenin and its effect on the protein levels of MDR1, MRP2, Bcl-2, Bax, MMP2, and MMP9. We found that USP9X and ß-catenin expressions in cisplatin-resistant cell lines (HNE1/DDP) were much higher than cisplatin-sensitive cell lines (HNE1) at both mRNA and protein levels. Co-IP assay demonstrated that USP9X was immunoprecipitated with ß-catenin in NPC cells. Knockdown of USP9X was able to partially reverse cisplatin resistance, increased cisplatin-induced apoptosis, and decreased the capacities of proliferation, migration, and invasion. Overexpression of USP9X can increase cisplatin resistance in NPC cells. Moreover, knockdown of USP9X expression can significantly reduce the expressions of MDR1, MRP2, Bcl-2, MMP2, and MMP9, but significantly increased the expression of Bax. These findings indicate that USP9X high expression plays a significant part in cisplatin resistance of NPC. This study elucidated the possible mechanism of cisplatin resistance in NPC cells and may have implications for the therapeutic reversal of cisplatin resistance.

FBW7 protects against spinal cord injury by mitigating inflammation-associated neuronal apoptosis in mice.

Spinal cord injury (SCI) leads to severe and long-lasting neurological disability. Presently, the lack of effective therapies for SCI is largely attributable to an incomplete understanding of its pathogenesis. F-box and WD repeat domain-containing protein 7 (FBW7, also known as FBXW7) is a type of E3 ubiquitin ligase complex, and plays essential roles in regulating different pathological and physiological processes. In this study, we attempted to explore the effects of FBW7 on SCI progression by the in vivo and in vitro experiments. SCI mice showed significantly reduced expression of FBW7 in spinal cord tissues. Promoting FBW7 expression via intrathecal injection of AAV9/FBW7 effectively improved locomotor function in SCI mice. Neuronal death in spinal cords of SCI mice was obviously ameliorated by FBW7 over-expression, along with greatly decreased expression of cleaved Caspase-3. In addition, microglial activation in spinal cord specimens was detected in SCI mice through increasing Iba-1 expression levels, which was, however, attenuated in SCI mice injected with AAV9/FBW7. Additionally, FBW7 over-expression dramatically restrained inflammatory response in spinal cord tissues of SCI mice, as evidenced by the down-regulated expression of tumor necrosis factor-α (TNF-α) and interleukin 1ß (IL-1ß) through blocking the activation of nuclear factor-κB (NF-κB) signaling. These anti-inflammatory effects of FBW7 were confirmed in LPS-stimulated mouse microglial BV2 cells. Finally, our in vitro studies showed that conditional medium (CM) collected from LPS-incubated BV2 cells markedly induced apoptosis in the isolated primary spinal neurons; However, this effect was overtly ameliorated by CM from LPS-exposed BV2 cells over-expressing FBW7. Thus, FBW7-regulated inflammation in microglial cells was involved in the amelioration of neuronal apoptosis during SCI development. Collectively, these findings illustrated that FBW7 expression was down-regulated in spinal cords of SCI mice, and promoting its expression could effectively mitigate SCI progression by repressing microglial inflammation and neuronal death.

Adiponectin Attenuates Streptozotocin-Induced Tau Hyperphosphorylation and Cognitive Deficits by Rescuing PI3K/Akt/GSK-3ß Pathway.

Clinical studies have demonstrated that decreased adiponectin is associated with the development of Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD). We focused on determining the neuroprotective effect offered by adiponectin against streptozotocin-induced brain damage in ICV-STZ rat model. We found that adiponectin supplements significantly restored the cognitive deficits in ICV-STZ rat model including shorter escape latency, more crossing times and increased time spent in the target quadrant. Adiponectin supplements also increased number of dendritic branches and mushroom percentage. In addition, adiponectin supplements attenuated tau hyperphosphorylation at multiple AD-related sites through activation of protein Ser9-phosphorylated glycogen synthase kinase-3ß (Ser9-GSK-3ß) with increased the Akt and PI3K activity. Our data suggest that adiponectin supplements have neuroprotective effects on the ICV-STZ rat model, which may be mediated by the activation of the PI3K/Akt/GSK-3ß signaling pathway.

Ketamine effect on HMGB1 and TLR4 expression in rats with acute lung injury.

Acute lung injury (ALI) is a common emergency and severe case in clinic. High mobility group protein box 1 (HMGB1) can be treated as a new anti-inflammatory treatment target. Toll-like receptor 4 (TLR4) is an important receptor of HMGB1. Ketamine is a widely used intravenous anesthetic with good anti-inflammatory and immune regulating function. Whether it can protect ALI through inhibiting HMGB1 and TLR4 expression in lung tissue still needs further investigation. Male SD rats were randomly divided into control, lipopolysaccharide (LPS) group and ketamine intervention group with 15 rats in each group. The rats were euthanatized at 24 h after modeling and the bronchoalveolar lavage fluid (BALF) was collected for HMGB1 and TLR4 level detection. Western Blot was applied to analyze HMGB1 and TLR4 protein expression in the lung tissue. HMGB1 and TLR4 concentration in BALF were 5.369 ± 1.564 ng/ml and 43.980 ± 7.524 pg/ml in the control, respectively. They were 12.358 ± 4.681 ng/ml and 102.538 ± 8.412 pg/ml in LPS group, and 7.399 ± 2.346 ng/ml and 87.208 ± 7.558 pg/ml in ketamine intervention group, respectively. Their levels increased significantly in LPS group and down-regulated after ketamine intervention. HMGB1 and TLR4 protein expression in lung tissue elevated obviously in LPS group, and decreased after ketamine treatment. HMGB1 and TLR4 protein level showed positive correlation in lung tissue (r = 0.921, P < 0.001). Ketamine can inhibit HMGB1 and TLR4 expression in ALI, and alleviate LPS induced rat lung injury.

[Effects of propofol and isoflurane on serum neuron-specific enolase level in surgical patients with acute craniocerebral trauma: a comparative study].

OBJECTIVE: To investigate changes in serum neuron-specific enolase (NSE) concentration in patients before, during and after surgery for acute craniocerebral trauma, and examine the effects of propofol and isoflurane on these changes. METHODS: Ten patients scheduled for urinary operation without cerebral injury were enrolled in the control group. Thirty patients with acute cerebral trauma were randomly allocated to propofol group (n=15) and isoflurane group (n=15). Serum concentrations of NSE before surgery, 2 h after the surgery began, and after completion of surgery were measured in all the patients by enzyme-linked immunoadsorbent assay. Glasgow scores of patients with cerebral trauma were also estimated and recorded. RESULTS: Serum concentration of NSE in patients with cerebral trauma were significantly higher than those in the control group before the surgery (P<0.01). The Glasgow score was inversely correlated with serum NSE concentration (r=-0.494, P<0.01). Serum NSE level after completion of surgery was significantly lower in propofol group than in isoflurane group (P<0.05). NSE levels at 2 h after the initiation of the surgery and after the completion of surgery were higher than those before the surgery. CONCLUSIONS: Serum NSE concentration increases in patients with acute cerebral injury in parallel to the severity of brain damage. Application of propofol by intravenous pumping can reduce the increase in serum NSE, alleviate cerebral injury, and protect the brain tissues of patients undergoing surgery for acute craniocerebral trauma.