General anesthetic agents induce neurotoxicity through astrocytes

Neuroscientists have recognized the importance of astrocytes in regulating neurological function and their influence on the release of glial transmitters.Few studies,however,have focused on the effects of general anesthetic agents on neuroglia or astrocytes.Astrocytes can also be an important target of general anesthetic agents as they exert not only sedative,analgesic,and amnesic effects but also mediate general anesthetic-induced neurotoxicity and postoperative cognitive dysfunction.Here,we analyzed recent advances in understanding the mechanism of general anesthetic agents on astrocytes,and found that exposure to general anesthetic agents will destroy the morphology and proliferation of astrocytes,in addition to acting on the receptors on their surface,which not only affect Ca^(2+)signaling,inhibit the release of brain-derived neurotrophic factor and lactate from astrocytes,but are even involved in the regulation of the pro-and anti-inflammatory processes of astrocytes.These would obviously affect the communication between astrocytes as well as between astrocytes and neighboring neurons,other neuroglia,and vascular cells.In this review,we summarize how general anesthetic agents act on neurons via astrocytes,and explore potential mechanisms of action of general anesthetic agents on the nervous system.We hope that this review will provide a new direction for mitigating the neurotoxicity of general anesthetic agents.

Human γδT-cell subsets and their involvement in tumor mmunity

γδT cells are a conserved population of innate lymphocytes with diverse structural and functional heterogeneity that participate in various immune responses during tumor progression. γδT cells perform potent immunosurveillance by exerting direct cytotoxicity, strong cytokine production and indirect antitumor immune responses. However, certain γδT-cell subsets also contribute to tumor progression by facilitating cancer-related inflammation and immunosuppression. Here, we review recent observations regarding the antitumor and protumor roles of major structural and functional subsets of human γδT cells, describing how these subsets are activated and polarized, and how these events relate to subsequent function in tumor immunity. These studies provide insights into the manipulation of γδT-cell function to facilitate more targeted approaches for tumor therapy.

Postoperative Regulatory T-Cells and Natural Killer Cells in Stage I Nonsmall Cell Lung Cancer Underwent Video-assisted Thoracoscopic Lobectomy or Thoracotomy

Background： Regulatory T-cells （Treg） play key roles in suppressing cell-mediated immunity in cancer patients. Little is known about perioperative Treg fluctuations in nonsmall cell lung cancer （NSCLC）. Video-assisted thoracoscopic （VATS） lobectomy, as a minimal invasive procedure for treating NSCLC, may have relatively less impact on the patient＇s immune system. This study aimed to observe perioperative dynamics of circulating Treg and natural killer （NK） cell levels in NSCLC patients who underwent major Iobectomy by VATS or thoracotomy. Methods： Totally, 98 consecutive patients with stage I NSCLC were recruited and assigned into VATS or thoracotomy groups. Peripheral blood samples were taken on 1-day prior to operation, postoperative days （PODs） I, 3, 7, 30, and 90. Circulating Treg and NK cell counts were assayed by flow cytometry, defined as CD4＋CD25＋CD127w cells in CD4＋ lymphocytes and CD56＋I6＋CD3 cells within CD45＋ leukocytes respectively. With SPSS software version 21.0 （SPSS Inc., USA）, differences between VATS and thoracotomy groups were determined by one-way analysis of variance （ANOVA）, and differences between preoperative baseline and PODs in each group were evaluated by one-way ANOVA Dunnett t-test. Results： In both groups, postoperative Treg percentages were lower than preoperative status. No statistical difference was found between VATS and thoracotomy groups on PODs 1, 3, 7, and 30. On POD 90, Treg percentage in VATS group was significantly lower than in thoracotomy group （5.26 ± 2.75 vs. 6.99 ±3.60, P = 0.012）. However, a higher level of NK was found on all PODs except on POD 90 in VATS group, comparing to thoracotomy group. Conclusions： Lower Treg level on POD 90 and higher NK levels on PODs 1, 3, 7, 30 in VATS group might imply better preserved cell-mediated immune function in NSCLC patients, than those in thoracotomy group.

Antibiotics-mediated intestinal microbiome perturbation aggravates tacrolimus-induced glucose disorders in mice

Both immunosuppressants and antibiotics (ABX) are indispensable for transplant patients. However, the former increases the risk of new-onset diabetes, whereas the latter impacts intestinal microbiota (IM). It is still unclear whether and how the interaction between immunosuppressants and ABX alters the IM and thus leads to glucose metabolism disorders. This study examined the alterations of glucose and lipid metabolism and IM in mice exposed to tacrolimus (TAC) with or without ABX. We found that ABX further aggravated TAC-induced glucose tolerance and increased insulin secretion. Combined treatment resulted in exacerbated lipid accumulation in the liver. TAC-altered microbial community was further amplified by ABX administration, as characterized by reductions in phylum Firmicutes, family Lachnospiraceae, and genus Copyococcus. Analyses based on the metagenomic profiles revealed that ABX augmented the effect of TAC on microbial metabolic function mostly related to lipid metabolism. The altered components of gut microbiome and predicted microbial functional profiles showed significant correlation with hepatic lipid accumulation and glucose disorders. In conclusion, ABX aggravated the effect of TAC on the microbiome and its metabolic capacities, which might contribute to hepatic lipid accumulation and glucose disorders. These findings suggest that the ABX-altered microbiome can amplify the diabetogenic effect of TAC and could be a novel therapeutic target for patients.

Systematic Review and Meta-Analysis of Acupuncture for Pain Caused by Liver Cancer

Objective:The objective of this study is to systematically review and analyze the efficacy of acupuncture for pain caused by primary liver cancer(PLC).Materials and Methods:We searched databases,including PubMed,Medline,Embase,Cochrane Library,Web of Science,China National Knowledge Infrastructure,Chinese Science and Technology Periodicals Database(VIP),Wanfang,and SinoMed/Chinese Biomedical Database(CBM),and retrieved randomized controlled trials(RCTs)that used acupuncture as the primary intervention to treat pain caused by PLC.Two investigators then screened the articles,extracted and pooled data,and evaluated the risk of bias of the included articles according to the Cochrane Handbook.RevMan5.3 was used for the meta-analysis of eligible RCTs.Results:A total of 145 articles were retrieved;after screening,8 RCTs involving 496 patients were eventually included in this meta-analysis.The results showed that acupuncture effectively improved cancer pain and was superior to Western medicine.Moreover,acupuncture was fast-acting for pain relief,prolonged the relief,and prevented relapse.Its adverse reaction rate was also significantly lower than that of Western medicine.No significant difference was observed in Visual Analog Scale score between acupuncture and Western medicine.Conclusion:Acupuncture relieves pain caused by liver cancer and can be used as an adjunct and alternative therapy for drug treatment.The existing research evidence is not yet objective or comprehensive,and more rigorous clinical trials are needed to validate the results.