Human placenta-derived mesenchymal stem cell administration protects against acute lung injury in a mouse model.

This study aims to investigate the effect of placenta-derived mesenchymal stem cells (PMSCs) administration on tissue repair following acute lung injury (ALI). PMSCs were transplanted intravenously to a mouse model of lipopolysaccharide-induced ALI. The therapeutic effects were determined by evaluating several indicators, including pathology; the wet/dry ratio of the lungs; blood gas analysis; the total protein content, cell numbers, and the activity of myeloperoxidase (MPO) in bronchial alveolar lavage fluid (BALF); and the levels of anti-inflammatory and proinflammatory cytokines in serum and BALF. To investigate the underlying mechanism, PMSC-derived exosomes were used for ALI treatment. Administration of PMSCs improved the degree of lung injury, reduced inflammation, increased the expression levels of anti-inflammatory cytokines, and protected lung function. As expected, the effects of PMSC-derived exosomes in the ALI model were similar to those of PMSCs, both in terms of improved lung function and reduced inflammation. These findings suggest that PMSCs have ameliorating effects on ALI that are potentially mediated via their secreted exosomes.

Effects of Sepsis Serum on the Fate of Adipose Tissue-Derived Stem Cells.

BACKGROUND: Adipose tissue-derived stem cells (ADSCs), a type of mesenchymal stem cell, have been used extensively in clinical trials for the treatment of multiple conditions, including sepsis. However, increasing evidence indicates that ADSCs vanish from tissues within days of administration. Consequently, it would be desirable to establish the mechanisms underlying the fate of ADSCs following transplantation. METHODS: In this study, sepsis serum from mouse models was used to mimic microenvironmental effects. Healthy donor-derived human ADSCs were cultured in vitro in the presence of mouse serum from normal or lipopolysaccharide (LPS)-induced sepsis models for the purposes of discriminant analysis. The effects of sepsis serum on ADSC surface markers and cell differentiation were analyzed by flow cytometry, and the proliferation of ADSCs was assessed using a Cell Counting Kit-8 (CCK-8) assay. Quantitative real-time PCR (qRT-PCR) was applied to assess the degree of ADSC differentiation. The effects of sepsis serum on the cytokine release and migration of ADSCs were determined based on ELISA and Transwell assays, respectively, and ADSC senescence was assessed by ß-galactosidase staining and western blotting. Furthermore, we performed metabolic profiling to determine the rates of extracellular acidification and oxidative phosphorylation and the production of adenosine triphosphate and reactive oxygen species. RESULTS: We found that sepsis serum enhanced the cytokine and growth factor secretion and migratory capacities of ADSCs. Moreover, the metabolic pattern of these cells was reprogrammed to a more activated oxidative phosphorylation stage, leading to an increase in osteoblastic differentiation capacity and reductions in adipogenesis and chondrogenesis. CONCLUSIONS: Our findings in this study reveal that a septic microenvironment can regulate the fate of ADSCs.

Effects of dexmedetomidine on postoperative sleep quality: a systematic review and meta-analysis of randomized controlled trials.

STUDY OBJECTIVES: To assess the effect of dexmedetomidine (DEX) on postoperative sleep quality using polysomnography (PSG) to identify possible interventions for postoperative sleep disturbances. METHODS: An electronic search of PubMed/MEDLINE, EMBASE, Cochrane Library and Web of Science was conducted from database inception to November 20, 2022. Randomized controlled trials (RCTs) on the effect of DEX administration on postoperative sleep quality using PSG or its derivatives were included. No language restrictions were applied. The sleep efficiency index (SEI), arousal index (AI), percentages of stage N1, N2 and N3 of non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep were measured in our meta-analysis. RESULTS: Five studies, involving 381 participants were included. Administration of DEX significantly improved SEI, lowered AI, decreased the duration of stage N1 sleep and increased the duration of stage N2 sleep compared to placebo groups. There were no significant differences in the duration of stage N3 sleep and REM sleep. DEX administration lowered the postoperative Visual Analogue Scale (VAS) score and improved the Ramsay sedation score with no adverse effect on postoperative delirium (POD). However, high heterogeneity was observed in most of the primary and secondary outcomes. CONCLUSIONS: Our study provides support for the perioperative administration of DEX to improve postoperative sleep quality. The optimal dosage and overall effect of DEX on postoperative sleep quality require further investigation using large-scale randomized controlled trials.

Dexamethasone in preventive analgesia alleviates pain and complications after jaw cyst enucleation: a randomized controlled trial.

BACKGROUND: Dexamethasone is widely used in the prevention of postoperative complications in oral surgery and strengthening the analgesic effect after anesthesia, but the efficacy is controversial, and the relationship between postoperative complications and pain is still unclear. The purpose of this study was to evaluate the analgesic effect of dexamethasone in the treatment of jaw cyst and to explore the relationship between postoperative complications and pain. METHODS: We conducted a prospective, randomized, double-blind clinical trial. 120 patients were divided into two groups, dexamethasone group ( group D) and control group (Group C). All patients were given 0.02 mg·kg-1 of hydromorphone to relieve pain in advance at 10 min before the beginning of operation. Meanwhile, dexamethasone was injected 0.2 mg·kg-1 intravenously in group D and normal saline was injected in group C. The primary endpoint was pain intensity at 2 h, 6 h, 12 h, 24 h and 48 h after surgery. The secondary endpoints were the incidence and extent of complications after surgery, including facial swelling and trismus. RESULTS: Compared with group C, the visual analogue scale (VAS) scores and occurrence of painful event postoperatively in group D were significantly lower both at rest (P < 0.0001 and P = 0.0014) and during mobilization (P < 0.0001 both). The degree of facial swelling and trismus in group D were significantly lower than that in group C at 24 h (P < 0.0001 and P = 0.00022) and 48 h (P < 0.0001 and P = 0.00015) after surgery, but there was no difference at 6 h and 12 h (P = 0.137 and P = 0.083) after surgery. The C-reactive protein (CRP) level at 24 h after operation in group D was lower than group C (P = 0.012), but there was no significant difference in blood glucose concentration between the two groups (P = 0.608). CONCLUSION: Dexamethasone can reduce the degree of facial swelling and trismus after jaw cyst surgery by inhibiting the production of inflammation, which alleviated the postoperative pain of patients significantly. In addition, it did not increase the risk of hyperglycemia. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry on May 07, 2020 (URL: http://www.chictr.org.cn/showproj.aspx?proj=53344 . Registry number: ChiCTR2000032693). Registered on 07/05/2020.

Clinical Observation of Patients Undergoing Glioma Surgery under Propofol and Sevoflurane Anesthesia: A Retrospective Study.

Objective: To observe the effects of propofol and sevoflurane anesthesia on patients undergoing glioma surgery. Methods: 192 patients with gliomas treated in our hospital from January 2016 to January 2021 were selected. All patients were randomly divided into observation group and control group. The observation group was given sevoflurane and the control group was given propofol. The clinical effects of the two groups were observed. Results: Comparison of clinical indexes related to intraoperative conditions between the two groups revealed that the time of anesthesia and extubation after operation in the observation group were shorter than those in the control group, and the difference was statistically significant (P < 0.05). The amount of intraoperative bleeding in the observation group was less than that in the control group, and the difference was statistically significant (P < 0.05). There was no significant difference in intracranial operation time, operation time, fluid volume, and urine volume between the two groups (P < 05). Comparing the recovery time of anesthesia between the two groups, the recovery time of orientation and the time of eye-opening in the observation group were significantly shorter than those in the control group (P < 0.05). Comparing the consciousness and cognitive function of the two groups, the OAAS score of the observation group after extubation, before leaving the operating room and 1 hour after extubation, was significantly higher than that of the control group (P < 0.05), and the MMSE score l h after extubation was significantly higher than that of the control group (P < 0.05). Comparing the incidence of postoperative complications between the two groups, the number of cases of restlessness, urinary infection, deep vein thrombosis, and hypertension in the observation group was lower than that in the control group, with statistical significance (P < 0.05). Conclusion: The anesthesia time and extubation time of the sevoflurane anesthesia group were shorter than that of the propofol anesthesia group, and the orientation recovery time and eye-opening time were shortened. The OAAS score of the sevoflurane anesthesia group was higher than that of the propofol anesthesia group after extubation, before extubation, and 1 hour after extubation. The probability of postoperative complications in the sevoflurane anesthesia group was lower than that in the propofol anesthesia group. Sevoflurane anesthesia may be more suitable for surgical induction of glioma patients than propofol anesthesia.

An Optimized Method for Adipose Stromal Vascular Fraction Isolation and its Application in Fat Grafting.

BACKGROUND: The stromal vascular fraction (SVF) derived from adipose tissue contains heterogeneous cell populations and has enormous potential for clinical therapy. There are two main methods for SVF isolation: enzymatic isolation and mechanical isolation, both of which have shortcomings. In this study, optimized conditions for the isolation of high-quality SVF were established, and applications in fat grafting were evaluated. METHODS: Adipose tissue was chopped into small pieces and then ground into an erosive shape using a syringe. The pieces were digested with 0.15% type II collagenase for 35 min at 37 °C. After centrifugation, the pellets were resuspended in DMEM and passed through a 100-µm strainer. The filtered cells were analyzed by flow cytometry. The fat graft was enriched with isolated SVF and subcutaneously transplanted into nude mice. Three weeks after transplantation, grafts were isolated, and H&E staining, immunocytochemistry, and western blotting were conducted. RESULTS: The harvested SVF cells reached > 2 × 106/ml of adipose tissue within 90 min of operation. The number of CD34+ ADSCs in our SVF pellets was > 6 × 105/ml of adipose tissue, which has the potential for differentiating into osteoblasts, adipocytes, and chondrocytes. Freshly collected adipose tissue is better for SVF isolation, and isolated SVF should also be kept at 4 °C and used as soon as possible. SVF may promote revascularization after fat grafting. The adipose tissue of an SVF co-transplanted group had an integral structure, clear capillaries, and higher VEGF expression. SVF co-transplantation inhibited adipose cell apoptosis. CONCLUSION: Our study provides an efficient procedure for SVF isolation, its application in fat grafting, and possible underlying mechanisms. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effects of intraoperative PEEP on postoperative pulmonary complications in high-risk patients undergoing laparoscopic abdominal surgery: study protocol for a randomised controlled trial.

INTRODUCTION: Postoperative pulmonary complications (PPCs), strongly associated with higher mortality risk, can develop in up to 58% of patients undergoing abdominal surgery. More and more evidence shows that the use of a lung-protective ventilation strategy has a lung protection effect in patients undergoing abdominal surgery, however, the role of positive end-expiratory pressure (PEEP) during the intraoperative period in preventing PPCs for laparoscopic surgery is not clearly defined. METHODS AND ANALYSIS: A total of 208 patients with a high risk of PPC, undergoing laparoscopic abdominal surgery, will be enrolled and randomised into a standard PEEP (6-8 cm H2O) group and a low PEEP (≤2 cm H2O) group. Both groups will receive a fraction of inspired oxygen of 0.50 and a tidal volume of 8 mL/kg ideal body weight (IBW). Standard perioperative fluid management and analgesic treatments are applied in both groups. The primary end point is PPC within 7 days after surgery. Secondary end points are the modified Clinical Pulmonary Infection Score, postoperative extrapulmonary complications, postoperative surgical complications, intensive care unit length of stay, hospital length of stay, 30-day mortality. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medicine College) (registration number KY2018026) on 22 October 2018. The first participant was recruited on 15 April 2019 and the estimated completion date of the study is October 2021. The results of this trial will be submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: http://www.chictr.org.cn, ID: ChiCTR1800019865. Registered on 2 December 2018; preresults.

Effects of intraoperative PEEP on postoperative pulmonary complications in patients undergoing robot-assisted laparoscopic radical resection for bladder cancer or prostate cancer: study protocol for a randomized controlled trial.

BACKGROUND: There are increasing studies showing that the use of a lung-protective ventilation strategy has a lung protection effect in patients undergoing abdominal surgery; however, the appropriate positive end-expiratory pressure (PEEP) has not yet defined. Adopting a suitable PEEP may prevent postoperative pulmonary complications. Robot-assisted laparoscopic surgery is the newest and most minimally invasive treatment for bladder cancer or prostate cancer. It is also necessary to consider the effects of Trendelenburg position with pneumoperitoneum on airway pressure and pulmonary function. The role of PEEP during the intraoperative period in preventing postoperative pulmonary complications for robot-assisted laparoscopic surgery is not clearly defined. METHODS/DESIGN: A total of 208 patients undergoing robot-assisted laparoscopic radical resection for bladder cancer or prostate cancer will be enrolled and then randomly assigned to a standard PEEP (6-8 cm H2O) group and a low PEEP (≤2 cm H2O) group. Both groups will receive an inspired oxygen fraction of 0.50 and a tidal volume of 8 mL/kg ideal body weight. Standard perioperative fluid management standardization and analgesic treatments will be applied in both groups. The primary endpoint is postoperative pulmonary complications within 7 days after surgery. Secondary endpoints are the modified clinical pulmonary infection score, postoperative extrapulmonary complications, postoperative surgical complications, intensive care unit length of stay, hospital length of stay, and 30-day mortality. DISCUSSION: This trial aimed to assess the effects of low tidal volumes combined with intraoperative PEEP ventilation strategy on postoperative pulmonary complications in patients undergoing robot-assisted laparoscopic radical resection for bladder cancer or prostate cancer. TRIAL REGISTRATION: ID: ChiCTR1800019867 . Registered on December 2, 2018.

Location- and Subunit-Specific NMDA Receptors Determine the Developmental Sevoflurane Neurotoxicity Through ERK1/2 Signaling.

It is well established that developmental exposure of sevoflurane (an inhalational anesthetic) is capable of inducing neuronal apoptosis and subsequent learning and memory disorders. Synaptic NMDA receptors activity plays an essential role in cell survival, while the extra-synaptic NMDA receptors activation is usually associated with cell death. However, whether synaptic or extra-synaptic NMDA receptors mediate developmental sevoflurane neurotoxicity is largely unknown. Here, we show that developmental sevoflurane treatment decreased NR2A, but increased NR2B subunit expression both in vitro and in vivo. Sevoflurane-induced neuronal apoptosis was attenuated by synaptic NMDA receptors activation or low dose of exogenous NMDA in vitro. Interestingly, these effects could be abolished by NR2A inhibitor PEAQX, but not NR2B inhibitor Ifenprodil in vitro. In contrast, activation of extra-synaptic NMDA receptors alone had no effects on sevoflurane neurotoxicity. In the scenario of extra-synaptic NMDA receptors stimulation, however, sevoflurane-induced neuronal apoptosis could be prevented by addition of Ifenprodil, but not by PEAQX in vitro. In addition, sevoflurane neurotoxicity could also be rescued by memantine, an uncompetitive antagonist for preferential blockade of extra-synaptic NMDA receptors both in vitro and in vivo. Furthermore, we found that developmental sevoflurane-induced phospho-ERK1/2 inhibition was restored by synaptic NMDA receptor activation (in vitro), low dose of NMDA (in vitro) or memantine (in vivo). And the neuroprotective role of synaptic NMDA activity was able to be reversed by MEK1/2 inhibitor U0126 in vitro. Finally, administration of memantine or NMDA significantly improved spatial learning and memory dysfunctions induced by developmental sevoflurane exposure without influence on locomotor activity. These results indicated that activation of synaptic NR2A-containing NMDA receptors, or inhibition of extra-synaptic NR2B-containing NMDA receptors contributed to the relief of sevoflurane neurotoxicity, and the ERK1/2 MAPK signaling may be involved in this process.

Blood pressure levels and prognosis of intracranial trauma patients with cognitive dysfunction.

OBJECTIVE: To evaluate the effects of blood pressure levels on prognosis of intracranial trauma patients with cognitive dysfunction. METHODS: One hundred and twenty intracranial trauma patients enrolled in our hospital from February 2011 to July 2013 were selected, including 40 hypertension and 80 non-hypertension cases. They were investigated by MiniMental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scales, and the clinical data were retrospectively analyzed. RESULTS: Compared with the control group, the MoCA, visuospatial executive function, attention, language, delayed recall, MMSE, orientation and memory scores of the hypertension group were significantly lower. Unconditional Logistic regression analysis showed that age, history of cerebrovascular disease and triglyceride level were the independent risk factors of cognitive function. CONCLUSION: The blood pressure levels of intracranial trauma patients were associated with cognitive function, with age, history of cerebrovascular disease and triglyceride level as the independent risk factors. Therefore, it is necessary to control blood pressure level to improve prognosis.