CSF-CN contributes to cancer-induced bone pain via the MKP-1-mediated MAPK pathway.

Pain is a major complication of cancer and significantly affects the quality of life. Cerebrospinal fluid-contacting nucleus (CSF-CN) has been reported to be involved in the development of neuropathic pain and inflammatory pain. However, whether CSF-CN contributes to cancer-induced bone pain (CIBP) remains unknown. In this study, we aimed to illustrate the role of CSF-CN in the pathogenesis of CIBP and identify its potential mechanism via the MKP-1-mediated MAPK pathway. The Walker 256 cancer cells were injected into the tibia cavity of female Sprague-Dawley rats to induce CIBP models. Intracerebroventricular injection of cholera toxin subunit B- saporin (CB-SAP) was performed to "knockout" the CSF-CN. Morphine and LV-MKP-1 were applied. Mechanical and thermal hyperalgesia behaviors, double immunofluorescence staining and Western blot were conducted after CIBP induction. The results revealed that CIBP significantly reduced the mechanical withdrawal threshold and the thermal threshold. Double immunofluorescence staining revealed that c-Fos-positive neurons in CSF-CN were significantly higher in the CIBP group than that in the sham group. Targeted ablation of CSF-CN dramatically aggravated pain sensitivity. Moreover, MKP-1 was down-regulated in the CSF-CN after CIBP induction. Pharmacological intervention with morphine significantly ameliorated the mechanical and thermal hyperalgesia through reversing the down-expression of MKP-1 in the CSF-CN on day 14 after CIBP induction. Mechanically, overexpression of MKP-1 by LV-MKP-1 injection significantly relieved CIBP via inhibiting the expression of phosphorylated p38, which subsequently decreased the protein levels of Bax, cleaved caspase-3 and Iba-1, and reduced the mRNA levels of IL-1ß, TNF-α and IL-6 in CSF-CN. In conclusion, CSF-CN contributed to CIBP via regulating the MKP-1-mediated p38-MAPK pathway. Future therapy targeting the expression of MKP-1 in the CSF-CN may be a promising new choice.

Comparison of Remifentanil-Based Fast-Track and Fentanyl-Based Routine Cardiac Anesthesia for Intraoperative Device Closure of Atrial Septal Defect (ASD) in Pediatric Patients.

BACKGROUND The aim of this study was to evaluate the effectiveness and safety of remifentanil-based fast-track anesthesia for intraoperative device closure of atrial septal defects (ASDs). MATERIAL AND METHODS The clinical data of 152 pediatric patients who received intraoperative device closure of ASD in our hospital from January 2015 to December 2017 were retrospectively analyzed. Patients were divided into 2 groups: group F (remifentanil-based fast-track anesthesia group, n=72) and group C (fentanyl-based routine anesthesia group, n=80). The relevant data from 2 groups were collected and analyzed. RESULTS No significant differences were found in the preoperative data or intraoperative hemodynamic index between these 2 groups. Group C was significantly inferior to group F regarding the duration of mechanical ventilation, length of intensive care unit (ICU) stay, length of hospital stay, and hospitalization expenses (P<0.05). In terms of postoperative complications, no death, third-degree atrioventricular block, occluder detachment, or residual leakage was reported in either group. The incidence of lung infections and bronchospasm was significantly higher in group C than in group F. There were no anesthetic-related complications. CONCLUSIONS The application of remifentanil-based fast-track anesthesia for intraoperative device closure of ASD is as effective and safe as fentanyl-based routine anesthesia. Moreover, remifentanil-based fast-track anesthesia has the advantages of shorter duration of mechanical ventilation, shorter length of hospital and ICU stay, fewer postoperative complications, and lower hospitalization expenses, and is therefore worthy of promotion in clinical practice.

The role of acute normovolemic hemodilution in reducing allogeneic blood transfusion in glioblastoma surgery: a case-control study.

BACKGROUND: Acute normovolemic hemodilution (ANH) was first introduced in glioblastoma surgery, and its role in reducing allogeneic blood transfusion was investigated in this study. METHODS: This study enrolled supratentorial glioblastoma patients who received total resection. In the ANH group, the patients were required to draw blood before the operation, and the blood will be transfused back to the patient during the operation. The association between ANH and clinical features was investigated. RESULTS: Sixty supratentorial glioblastoma patients were enrolled in this study, 25 patients were allocated in the ANH group, and another 35 patients were included in the control group. ANH dramatically reduced the need for allogeneic blood transfusion (3 [12%] vs 12 [34.3%], P = 0.049), and the blood transfusion per total of patients was dramatically decreased by the application of ANH (0.40 ± 1.15 units vs 1.06 ± 1.59 units, P = 0.069). Furthermore, ANH also markedly reduced the requirement of fresh frozen plasma (FFP) transfusion (2 [8%] vs 11 [31.4%], P = 0.030) and the volume of FFP transfusion per total of patients (32.00 ± 114.46 mL vs 115.71 ± 181.00 mL, P = 0.033). The complication rate was similar between the two groups. CONCLUSIONS: ANH was a safe and effective blood conservation technique in glioblastoma surgery.

Ultrasonic evaluation of metoclopramide's effect on gastric motility in emergency trauma patients.

Objective: The present study aimed to use bedside ultrasound to evaluate the effects of metoclopramide on gastric motility in patients being treated for trauma in the emergency department. Methods: Fifty patients underwent an ultrasound immediately after attending the emergency department of Zhang Zhou Hospital due to trauma. The patients were randomly divided into two groups: a metoclopramide group (group M, n = 25) and a normal saline group (group S, n = 25). The cross-sectional area (CSA) of the gastric antrum was measured at 0, 30, 60, 90, and 120 min (T = time). The gastric emptying rate (GER, GER=-AareaTn/AareaTn-30-1×100), GER/min (GER divided by the corresponding interval time), gastric content properties, Perlas grade at different time points, T120 gastric volume (GV), and GV per unit of body weight (GV/W) were evaluated. The risk of vomiting, reflux/aspiration, and type of anesthetic treatment were also evaluated. Results: The differences between the two groups in the CSA of the gastric antrum at each time point were statistically significant (p < 0.001). The CSAs of the gastric antrum in group M were lower than those in group S, and the greatest difference between the two groups occurred at T30 (p < 0.001). The differences between the two groups in GER and GER/min were also statistically significant (p < 0.001); those differences in group M were higher than those in group S, and the greatest differences between the two groups occurred at T30 (p < 0.001). There were no obvious change trends in the properties of the gastric contents and the Perlas grades in either group, and the differences between the two groups were not statistically significant (p = 0.97). The differences between the two groups in the GV and GV/W at T120 were statistically significant (p < 0.001), as was the risk of reflux and aspiration at T120 (p < 0.001). Conclusion: When metoclopramide was used in satiated emergency trauma patients, it accelerated gastric emptying within 30 min and reduced the risk of accidental reflux. However, a normal gastric emptying level was not achieved, which can be attributed to the delaying effect of trauma on gastric emptying.

The Use of Acute Normovolemic Hemodilution in Clipping Surgery for Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The occurrence of coronavirus disease 2019 (COVID-19) has overwhelmed the blood supply chain worldwide and severely influenced clinical procedures with potential massive blood loss, such as clipping surgery for aneurysmal subarachnoid hemorrhage (aSAH). Whether acute normovolemic hemodilution (ANH) is safe and effective in aneurysm clipping remains largely unknown. METHODS: Patients with aSAH who underwent clipping surgery within 72 hours from bleeding were included. The patients in the ANH group received 400 mL autologous blood collection, and the blood was returned as needed during surgery. The relationships between ANH and perioperative allogeneic blood transfusion, postoperative outcome, and complications were analyzed. RESULTS: Sixty-two patients with aSAH were included between December 2019 and June 2020 (20 in the ANH group and 42 in the non-ANH group). ANH did not reduce the need of perioperative blood transfusion (3 [15%] vs. 5 [11.9%]; P = 0.734). However, ANH significantly increased serum hemoglobin levels on postoperative day 1 (11.5 ± 2.5 g/dL vs. 10.3 ± 2.0 g/dL; P = 0.045) and day 3 (12.1 ± 2.0 g/dL vs. 10.7 ± 1.3 g/dL; P = 0.002). Multivariable analysis indicated that serum hemoglobin level on postoperative day 1 (odds ratio, 0.895; 95% confidence interval, 0.822-0.973; P = 0.010) was an independent risk factor for unfavorable outcome, and receiver operating characteristic curve analysis showed that it had a comparable predictive power to World Federation of Neurosurgical Societies grade (Z = 0.275; P > 0.05). CONCLUSIONS: ANH significantly increased postoperative hemoglobin levels, and it may hold the potential to improve patients' outcomes. Routine use of ANH should be considered in aneurysm clipping surgery.

Optimal concentration of the transversus abdominis plane block in enhanced recovery after surgery protocols for patients of advanced age undergoing laparoscopic rectal cancer surgery.

OBJECTIVE: The transversus abdominis plane (TAP) block ameliorates visual analogue scale scores and decreases morphine requirements, but its role remains unclear. Patients of advanced age are susceptible to local anesthetic intoxication. We aimed to identify an optimal concentration that can be used in enhanced recovery after surgery (ERAS) without compromising analgesic efficacy. METHODS: In total, 120 patients aged ≥65 years undergoing laparoscopic rectal cancer surgery received general anesthesia combined with a TAP block using 0.25% ropivacaine (Group A), 0.50% ropivacaine (Group B), or 0.75% ropivacaine (Group C) in a 40-mL volume. Group D only received general anesthesia. Epinephrine, plasma cortisol, interleukin-6, and tumor necrosis factor-α were measured at baseline, skin incision, celiac exploration, and tracheal extubation. The proportions of CD4+ and CD4+/CD8+ cells were measured at baseline and postoperative days 1 and 3. RESULTS: The TAP block relieved the stress response and accelerated intestinal functional recovery as shown by significant reductions in VAS scores and anesthetic requirements. However, there was no significant difference between Groups B and C. CONCLUSION: The TAP block plays an important role in ERAS in older patients undergoing laparoscopic rectal cancer surgery, and 0.5% ropivacaine is an optimal concentration that can reduce toxicity without undermining analgesia.

Effect of goal-directed fluid therapy on early cognitive function in elderly patients with spinal stenosis: A Case-Control Study.

PURPOSE: To explore effect of goal-directed fluid therapy (GDFT) on early cognitive function in elderly patients with spinal stenosis. METHODS: 83 elderly patients with spinal stenosis were randomly classified into two groups: control group (n = 40) and GDFT group (n = 43). The Montreal Cognitive Assessment (MoCA) score, IL-6 and S100ß levels, hemodynamic parameters, cerebral oxygen saturation (rSO2), arterial lactic acid values, output of surgery, operation time and cases of hypotension, intraoperative complications within 7 days were recorded for all patients. RESULTS: The incidence of postoperative cognitive dysfunction (POCD) was about 21.67% in this study. The MoCA scores, inflammatory mediators, perfusion indexes (rSO2 and lactic acid)and intraoperative hemodynamics(HR, MAP, and CI)were not all the same at different time points (P < 0.05). The levels of inflammatory mediators (IL-6 and S100ß) in GDFT group were lower than those in the control group (P < 0.05). Total intake, amount of lactated Ringer's solution and cases of hypotension in GDFT group were significantly lower than control group (P < 0.05), but amount of voluven was higher than control group(P < 0.05). Compared with control group, the incidence of postoperative delirium, nausea and vomiting, and hypotension in GDFT group was lower (P < 0.05). CONCLUSIONS: GDFT can maintain the stability of perioperative hemodynamics in the prone position of elderly patients with spinal stenosis, improve the balance between perfusion of tissue and organ and supply and demand of oxygen, reduce the inflammatory response, and reduce the incidence of early POCD in this type of surgery.

Sodium hydrosulfide relieves neuropathic pain in chronic constriction injured rats.

Aberrant neuronal activity in injured peripheral nerves is believed to be an important factor in the development of neuropathic pain (NPP). Channel protein pCREB of that activity has been shown to mitigate the onset of associated molecular events in the nervous system, and sodium hydrosulfide (NaHS) could inhibit the expression of pCREB. However, whether NaHS could relieve the pain, it needs further experimental research. Furthermore, the clinical potential that NaHS was used to relieve pain was limited so it would be required. To address these issues, the rats of sciatic nerve chronic constriction injury (CCI) were given intraperitoneal injection of NaHS containing hydrogen sulfide (H2S). The experimental results showed that NaHS inhibited the reduction of paw withdrawal thermal latency (PWTL), mechanical withdrawal threshold (MWT), and the level of pCREB in CCI rats in a dose-dependent manner and they were greatly decreased in NaHSM group (P < 0.05). NaHS alleviates chronic neuropathic pain by inhibiting expression of pCREB in the spinal cord of Sprague-Dawley rats.

A two-year follow-up study of cotransplantation with neural stem/progenitor cells and mesenchymal stromal cells in ischemic stroke patients.

Stem cell therapy is an emerging therapeutic modality in the treatment of stroke. We assessed the safety and feasibility of the cotransplantation of neural stem/progenitor cells (NSPCs) and mesenchymal stromal cells (MSCs) in patients with ischemic stroke. Eight patients were enrolled in this study. All patients had a hemisphere with infarct lesions located on one side of the territories of the cerebral middle or anterior arteries as revealed with cranial magnetic resonance imaging (MRI). The patients received one of the following two types of treatment: the first treatment involved four intravenous injections of MSCs at 0.5 × 10(6)/kg body weight; the second treatment involved one intravenous injection of MSCs at 0.5 × 10(6)/kg weight followed by three injections of MSCs at 5 × 10(6)/patient and NSPCs at 6 × 10(6)/patient through the cerebellomedullary cistern. The patients' clinical statuses were evaluated with the National Institutes of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), and the Barthel index (BI). Six patients were given four cell transplantations. The most common side effect of stem cell transplantation in these six cases was low fever that usually lasted 2-4 days after each therapy. One patient exhibited minor dizziness. All side effects appeared within the first 2-24 h of cell transplantation, and they resolved without special treatment. There was no evidence of neurological deterioration or neurological infection. Most importantly, no tumorigenesis was found at a 2-year follow-up. The neurological functions, disability levels, and daily living abilities of the patients in this study were improved. While these observations support the use of the combination transplantation of NSPCs and MSCs as a safe and feasible method of improving neurological function, further studies that include larger samples, longer follow-ups, and control groups are still needed. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.

Relationship between EEG beta power abnormality and early diagnosis of cognitive impairment post cerebral hemorrhage.

Cerebral hemorrhage is a common disease of older adults, which could increase the risk of cognitive impairment. Electroencephalogram (EEG) characteristics can be analyzed to investigate the applied value in the assessment of cognitive impairment of the patients with cerebral hemorrhage. One hundred eighty-two patients (including patients with cognitive impairment [CHCI] and patients with cognitive normality [CHNC] with cerebral hemorrhage, and 120 normal healthy persons [control; CN]) were recruited between July 2008 to March 2012 at the department of neurology. All patients were analyzed by EEG, and analysis results were compared to the Montreal Cognitive Assessment (MoCA) scale, using the methods of correlation analysis, clustering analysis, and concordance analysis. The results indicated that patients with CHCI had significantly lower EEG beta power (0.814 ± 0.113 mcV(2)) relative to CHNC (1.601 ± 0.186 mcV(2), P < .01) or CN group (1.713 ± 0.201 mcV(2), P < .01). Significant negative correlation was found between the beta power and hemorrhage region, age, hemorrhage size, hemorrhage amount (r 1 = -.92223, r 2 = -.81084, r 3 = -.79258, r 4 = -.84961, respectively, all P < .001). There was good concordance between K-means clustering algorithm calculating the beta power and MoCA scoring (Kappa = 0.899, P < .001). In conclusion, the preliminary findings suggest that the recognition techniques of EEG hold considerable promise for the assessment of cognitive impairment post cerebral hemorrhage, which negatively related to the hemorrhage region, hemorrhage size, hemorrhage amount, and age.

Construction of a bicistronic recombinant adenoviral vector for human interleukin-10 and enhanced green fluorescent protein expression in bone marrow mesenchymal stem cells.

BACKGROUND: Human interleukin-10 (hIL-10) is a cytokine synthesis inhibitory factor, which is involved in various immune responses. The purpose of this study was to construct an adenoviral vector carrying the hIL-10 gene for expression of biologically active hIL-10 in rat bone marrow mesenchymal stem cells (rMSCs). METHODS: A pSNAV2.0-hIL10 plasmid was used as a template to obtain a hIL-10 cDNA fragment that was subcloned by restriction enzyme digestion and ligation into a pDC316-IRES-EGFP-lacZ alpha plasmid carrying an enhanced green fluorescent protein (EGFP) marker gene. The pDC316-hIL-10-IRES-EGFP plasmid was linearized by PmeI digestion and used to transfect HEK293 packaging cells using the adenovirus packaging system AdMax. Virus particles were amplified by repeatedly infecting HEK293 cells with the seed virus and then purified by ion exchange. After the number of virus particles and titer was determined, rMSCs were infected with the adenoviral vector. The infection rate was determined by fluorescence microscopy and flow cytometry, and hIL-10 protein expression in rMSCs was measured by Western blotting. RESULTS: The virus particle concentration, OD260/280 value and virus titer of the amplified and purified recombinant adenovirus were 3.2 × 10(11) VP/ml, approximately 2.0, and 1.1 × 10(10) TCID50/ml, respectively. Bright green fluorescence was observed by fluorescence microscopy and flow cytometry in the recombinant adenovirus-infected rMSCs. GFP expression was considered the multiplicity of infection (MOI) and was time-dependent. The infection rate was 92.9% at 100 MOI. CONCLUSIONS: A bicistronic recombinant adenoviral vector for hIL-10 and EGFP gene expression were successfully constructed. The infection rate of rMSCs by the adenovirus was high (92.9% at 100 MOI) and the target gene hIL-10 was highly expressed in cells. The present study provides an experimental basis for further research of immunosuppressive therapy using hIL-10. The expression level of hIL-10 protein as detected by Western blotting was also MOI- and time-dependent.