Neuroinflammation plays a major role in postoperative cognitive dysfunction (POCD). Accumulated evidence indicates that cannabinoid receptor type 2 (CB2R) can mediate anti-inflammatory and immunomodulatory effects in part by controlling microglial activity. However, the impact of CB2R on postoperative cognition has not been investigated. We hypothesized that CB2R is involved in surgery-induced cognitive impairment in adult mice. Adult C57BL/6 mice were subjected to intramedullary fixation surgery for tibial fracture under isoflurane anesthesia and CB2R agonist (JWH133) or CB2R antagonist (AM630) treatment. The mice were trained 24 h prior to surgery using a fear conditioning protocol and assessed in a novel context on postoperative days 1, 3, and 7 to evaluate cognitive function. Open-field testing was performed to evaluate the locomotor activity of the mice. The expression levels of IL-1β, TNF-α, MCP-1, and CB2R in the hippocampus and prefrontal cortex were assessed by Western blotting; the expression of microglial marker CD11b in the CA1 area of the hippocampus and medial prefrontal cortex was assessed by immunostaining. The mice displayed no changes in locomotor activity after surgery and drug treatments. The mice exhibited impaired hippocampal-dependent memory accompanied by an increased expression of proinflammatory factors in the hippocampus and prefrontal cortex 1, 3, and 7 days after surgery, while hippocampal-independent memory remained unaffected at the same time points. JWH133 treatment attenuated surgery-induced memory loss, while AM630 treatment aggravated surgery-induced memory loss, paralleled by a decreased or increased expression of proinflammatory factors in the hippocampus and prefrontal cortex. The expression of CB2R in the hippocampus and prefrontal cortex was upregulated following surgery; however, it was downregulated by postoperative treatment with JWH133. Similarly, the expression of CD11b in the CA1 area of the hippocampus and medial prefrontal cortex was upregulated following surgery and downregulated by postoperative treatment with JWH133. These findings indicate that CB2R may modulate the neuroinflammatory and cognitive impairment in a mouse model of orthopedic surgery, and the activation of CB2R may effectively ameliorate the hippocampal-dependent memory loss of mice in the early postoperative stage.

Background: Alzheimer's disease, the most common form of dementia, has tremendous social and economic impact worldwide. This study aimed to analyze global trends in Alzheimer's disease research and to investigate China's contribution to this research. Methods: The quantity and influence of publications related to Alzheimer's disease in China and elsewhere were compared. The Web of Science (WOS) and PubMed databases were searched from 1988 to 2017 using the terms "Alzheimer's disease" or "Alzheimers disease." Global Alzheimer's disease publications were classified and analyzed. Keywords, countries, and institutions publishing articles on Alzheimer's disease were analyzed, and citations of these articles were examined. Results: A total of 181,116 articles regarding Alzheimer's disease research were identified and analyzed. Neuroscience and neurology were the main research categories both globally and in China. Basic research dominated Alzheimer's publications, accounting for 30.93% of global publications and 95.31% of publications in China. A total of 8,935 journals published articles related to Alzheimer's disease. The journal Neurobiology of Aging published the most Alzheimer's disease-related articles, numbering 5,206 over the time period examined. The National Institutes of Health, the National Institute on Aging, and the Department of Health and Human Services jointly sponsored 11,809 articles, ranking first in the world. The National Natural Science Foundation of China funded the largest number of studies on Alzheimer's disease in China and recognized the importance of traditional Chinese medicine in Alzheimer's disease research. Conclusions: The present study provides data for global researchers to understand research perspectives and develop future research directions. In recent years, Chinese researchers have contributed significantly to global Alzheimer's research. Still, strengthening international cooperation could improve the quality and number of publications regarding Alzheimer's disease.

Aim: Astrocytes are connected by gap junctions Connexin43 (GJs‐Cx43) forming an extensive intercellular network and maintain brain homeostasis. Perioperative neurocognitive disorder (PND) occurs frequently after anesthesia/surgery and worsens patient outcome, but the neural circuit mechanisms remain unclear. This study aimed to determine the effects of the GJs‐Cx43–mediated astrocytic network on PND and ascertain the underlying neural circuit mechanism.Methods: Male C57BL/6 mice were treated with long‐term isoflurane exposure to construct a mouse model of PND. We also exposed primary mouse astrocytes to long‐term isoflurane exposure to simulate the conditions of in vivo cognitive dysfunction. Behavioral tests were performed using the Y‐maze and fear conditioning (FC) tests. Manganese‐enhanced magnetic resonance imaging (MEMRI) and resting‐state functional magnetic resonance imaging (rs‐fMRI) were used to investigate brain activity and functional connectivity. Western blot and flow cytometry analysis were used to assess protein expression.Results: Reconfiguring the astrocytic network by increasing GJs‐Cx43 expression can modulate 22 subregions affected by PND in three ways: reversed activation, reversed inhibition, and intensified activation. The brain functional connectivity analysis further suggests that PND is a brain network disorder that includes sleep‐wake rhythm–related brain regions, contextual and fear memory–related subregions, the hippocampal‐amygdala circuit, the septo‐hippocampal circuit, and the entorhinal‐hippocampal circuit. Notably, remodeling the astrocytic network by upregulation of GJs‐Cx43 can partially reverse the abnormalities in the above circuits. Pathophysiological degeneration in hippocampus is one of the primary hallmarks of PND pathology, and long‐term isoflurane anesthesia contributes to oxidative stress and neuroinflammation in the hippocampus. However, promoting the formation of GJs‐Cx43 ameliorated cognitive dysfunction induced by long‐term isoflurane anesthesia through the attenuation of oxidative stress in hippocampus.Conclusion: Enhancing GJs‐Cx43 coupling can improve brain network abnormalities and cognitive impairment induced by long‐term isoflurane anesthesia, its mechanisms might be associated with the regulation of oxidative stress and neuroinflammation.

Objectives. To assess the association between short-term postoperative cognitive dysfuction (POCD) and inflammtory response in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Design. A prospective cohort study. Setting. University medical centre. Participants. Fifty-one adult patients who had undergone CRS-HIPEC and twenty control participants. Measurements. The inflammatory marker levels in plasma and cognitive function were measured. Results. Twenty (39.2%, 20/51) patients developed POCD at 1 w after CRS-HIPEC. The patients with POCD had higher serum interleukin 1β (IL-1β), serum amyloid A (SAA), S100 calcium-binding protein β (S-100β), and high mobility group box-1 protein (HMGB-1) levels at 1 and 24 h postoperatively than patients without POCD. There was an association between POCD and the maximum IL-1β and S-100β concentrations in serum, which remained following adjustment for age and FBS. Conclusion. In this pilot study, perioperative inflammatory marker levels increase significantly after CRS-HIPEC in adult patients, and such elevations are associated with the development of short-term cognitive dysfunction after this complex surgery. These results suggested the need for a larger RCT to replicate and confirm these findings.

Timosaponin A‑III (TAIII) is a saponin isolated from anemarrhena asphodeloides and possesses the inhibitory effect on proliferation of multiple tumor cells. In the present study, the antitumor effect of TAIII and its underlying molecular mechanisms were investigated in vitro in T‑cell acute lymphoblastic leukemia (T‑ALL) Jurkat cells. The results demonstrated that TAIII inhibits the viability of Jurkat cells in a time‑ and dose‑dependent manner, and induces apoptosis of Jurkat cells in a dose‑dependent manner. Transmission electron microscopy demonstrated the formation of numerous autophagosomes in TAIII‑treated Jurkat cells. Furthermore, monodansylcadaverine (MDC)‑labeled autophagic vacuoles were observed following TAIII treatment by an inverted fluorescence microscope and MDC accumulation increased notably in TAIII treatment groups in a concentration‑dependent manner. B‑cell lymphoma‑2 (Bcl‑2)‑associated X (Bax) was upregulated while Bcl‑2 was reduced following TAIII treatment, indicating that the pro‑apoptotic mechanism of TAIII may be associated with upregulation of Bax. Further investigation revealed that TAIII promotes the expression of autophagy‑associated proteins Beclin 1 and LC3‑II, and inhibits the phosphoinositide 3‑kinase/Akt/mechanistic target of rapamycin kinase pathway. The present study revealed that the antitumor activity of TAIII was primarily achieved by the induction of cell apoptosis and autophagy, indicating a promising potential as a novel effective reagent against T‑ALL.