Purpose: Quadratus lumborum block (QLB) is shown to be effective on analgesia following cesarean section. This study aimed to compare the effects of three practical QLB approaches and classic epidural analgesia (EA) for cesarean section under spinal anesthesia. Patients and methods: Parturients undergoing elective cesarean section were randomized as group 1 (QLB type 2), group 2 (QLB type 3), group 3 (QLB type 2+3) and group 4 (EA). The block was performed at the end of the operation, and the epidural group was given a single epidural bolus. All subjects were provided with intravenous patient-controlled analgesia under identical settings. In addition, the postoperative pain severity was assessed by the VAS, which together with the morphine consumption at specific time intervals, was recorded within 48 hrs after surgery. Data were collected from December 2017 to June 2018. Results: A total of 94 parturients had completed the study. At almost all postoperative time points, the VAS scores at rest and with movement in QLB type 2+3 group were lower than those in QLB type 2 or 3 group. The mean additional morphine consumption in QLB type 2+3 group (2.7 mg) was lower than that in QLB type 2 or 3 group (6.1 mg and 5.7 mg, respectively) within 48 h after surgery (P<0.001). Besides, the total morphine consumption in EA group (1.3 mg) was lower than that in any other QLB group (P<0.001). Conclusions: The analgesic effect of QLB is highly dependent on the injection position of local anesthetic. Besides, the ultrasound-guided QLB type 2+3 can provide superior analgesic effect following cesarean section to that of QLB type 2 or 3 block. However, it remains to be further validated about whether the combination of QLB type 2 and 3 is the best approach.

Objective: The aim was to determine preoperative gut microbiota metabolites that may be associated with postoperative delirium (POD) development in patients and further study in rodents. Summary Background Data: POD occurs in 9% to 50% of older patients undergoing anesthesia/surgery but lacks effective treatments or prevention. High-throughput metabolomics using liquid chromatography with tandem mass spectrometry has accelerated disease-related biomarkers discovery. We performed metabolomic studies in humans to identify potential metabolite biomarkers linked to POD and examined potential mechanisms in rodents. Methods: We performed a prospective observational cohort study to examine the metabolomic changes that were associated with the development of POD. Then the gut microbiota-related metabolomic changes were recapitulated by gut microbiota perturbation in rodents. POD was assessed in mice using a battery of behavioral tests including novel objective test, Y-maze test, open-field test, and buried food test. The mechanisms through which gut microbiota-related metabolomic changes influenced POD were examined using chemogenetics. Results: Indole-3-propionic acid (IPA) is a gut microbiota metabolite that belongs to the indole family. Baseline plasma levels of IPA were significantly inversely correlated with the onset of POD in 103 (17 cases) human individuals. This relationship was validated in preclinical mouse models for POD: reducing IPA levels through gut microbiota perturbation promoted POD-like behavior. More importantly, IPA administration deterred POD-like behavior. Colonization of germ-free mice with mutant Clostridium sporogenes that did not produce IPA-promoted POD-like behavior. Chemogenetic studies revealed that the protective effect of IPA in mice was mediated, in part, by peroxisome proliferator-activated receptor gamma coactivator 1-alpha in hippocampal interneurons. Conclusions: Gut microbiota-derived IPA is an important molecule implicated in the pathogenesis of POD, which could potentially be harnessed for POD prevention.

Bone-derived mesenchymal stem cell (BMSC) transplantation has been reported to be effective for the treatment of ischemic heart disease, but whether BMSCs are the optimal cell type remains under debate. Increasing numbers of studies have shown that Nestin, an intermediate filament protein, is a potential marker for MSCs, which raises the question of whether Nestin+ cells in BMSCs may play a more crucial role in myocardial repair. Nestin+ cells were isolated using flow cytometry by gating for CD45− Ter119− CD31− cells from the compact bone of Nestin-GFP transgenic mice, expressing GFP driven by the Nestin promoter. Colony-forming and proliferative curve assays were conducted to determine the proliferative capacity of these cells, while qRT-PCR was used to analyze the mRNA levels of relative chemokines and growth factors. Cardiac endothelial cell (CEC) recruitment was assessed via a transwell assay. Moreover, permanent ligation of the left anterior descending (LAD) coronary artery was performed to establish an acute myocardial infarction (AMI) mouse model. After cell transplantation, conventional echocardiography was conducted 1 and 4 weeks post-MI, and hearts were harvested for hematoxylin-and-eosin (HE) staining and immunofluorescence staining 1 week post-MI. Further evaluation of paracrine factor levels and administration of a neutralizing antibody (TIMP-1, TIMP-2, and CXCL12) or a CXCR4 antagonist (AMD3100) in MI hearts were performed to elucidate the mechanism involved in the chemotactic effect of Nestin+ BMSCs in vivo. Compared with Nestin− BMSCs, a greater proliferative capacity of Nestin+ BMSCs was observed, which further exhibited moderately high expression of chemokines instead of growth factors. More CEC recruitment in the Nestin+ BMSC-cocultured group was observed in vitro, while this effect was obviously abolished after treatment with neutralizing antibodies against TIMP-1, TIMP-2, or CXCL12, and more importantly, blocking the CXCL12/CXCR4 axis with a AMD3100 significantly reduced the chemotactic effect of Nestin+ BMSCs. After transplantation into mice exposed to myocardial infarction (MI), Nestin+ BMSC-treated mice showed significantly improved survival and left ventricular function compared with Nestin− BMSC-treated mice. Moreover, endogenous CECs were markedly increased, and chemokine levels were significantly higher, in the infarcted border zone with Nestin+ BMSC treatment. Meanwhile, neutralization of each TIMP-1, TIMP-2, or CXCL12 in vivo could reduce the left ventricular function at 1 and 4 weeks post-MI; importantly, the combined use of these three neutralizing antibodies could make a higher significance on cardiac function. Finally, blocking the CXCL12/CXCR4 axis with AMD3100 significantly reduced the left ventricular function and greatly inhibited Nestin+ BMSC-induced CEC chemotaxis in vivo. These results suggest that Nestin+ BMSC transplantation can improve cardiac function in an AMI model by recruiting resident CECs to the infarcted border region via the CXCL12/CXCR4 chemokine pathway. And we demonstrated that Nestin+BMSC-secreted TIMP-1/2 enhances CXCL12(SDF1α)/CXCR4 axis-driven migration of endogenous Sca-1+ endothelial cells in ischemic heart post-AMI. Taken together, our results show that Nestin is a useful marker for the identification of functional BMSCs and indicate that Nestin+ BMSCs could be a better therapeutic candidate for cardiac repair.

The commonly used inhalation anesthetic, sevoflurane, has been previously demonstrated to induce apoptosis in the developing brain; however, the underlying molecular mechanisms remain largely unknown. MicroRNAs (miRNAs) serve important roles in multiple physiological/pathological processes, such as cell death and survival. In the present study, the miRNA sequence that was most closely associated with sevoflurane‑induced apoptosis in the hippocampus of neonatal rat brains was identified. Seven‑day‑old Sprague Dawley rats were first exposed to 2.3% sevoflurane for 6 h. Hippocampal brain tissues were harvested at 6 h following sevoflurane exposure. Cleaved caspase‑3 levels were examined using an immunofluorescence assay. Alterations in miRNA expression were assessed by microarray analysis and reverse transcription-quantitative polymerase chain reaction. The protein levels of p53, phosphorylated (p)‑p53, B-cell lymphoma-2 (Bcl-2) and Bax were assessed by western blot analysis. Sevoflurane exposure significantly increased the levels of cleaved caspase‑3 in the hippocampus. In addition, among the 688 miRNAs that were observed to be expressed in the hippocampus, sevoflurane exposure altered the expression levels of 266 miRNAs. Among these differentially expressed miRNAs, eight were significantly upregulated and one (miRNA‑34c) was significantly downregulated following sevoflurane exposure. Bioinformatics analyses indicated the miRNA‑34c was a direct downstream target of p53. Sevoflurane exposure induced significant alterations in the level of p‑p53, Bcl‑2 and Bax in the hippocampus of neonatal rats. In conclusion, the results of the present study suggest that miRNA‑34c may be regulated by p53 and is involved in sevoflurane‑induced neural apoptosis in the hippocampus of developing rat brains, potentially via the mitochondrial pathway.