Effective multi-modal clustering method via skip aggregation network for parallel scRNA-seq and scATAC-seq data.

In recent years, there has been a growing trend in the realm of parallel clustering analysis for single-cell RNA-seq (scRNA) and single-cell Assay of Transposase Accessible Chromatin (scATAC) data. However, prevailing methods often treat these two data modalities as equals, neglecting the fact that the scRNA mode holds significantly richer information compared to the scATAC. This disregard hinders the model benefits from the insights derived from multiple modalities, compromising the overall clustering performance. To this end, we propose an effective multi-modal clustering model scEMC for parallel scRNA and Assay of Transposase Accessible Chromatin data. Concretely, we have devised a skip aggregation network to simultaneously learn global structural information among cells and integrate data from diverse modalities. To safeguard the quality of integrated cell representation against the influence stemming from sparse scATAC data, we connect the scRNA data with the aggregated representation via skip connection. Moreover, to effectively fit the real distribution of cells, we introduced a Zero Inflated Negative Binomial-based denoising autoencoder that accommodates corrupted data containing synthetic noise, concurrently integrating a joint optimization module that employs multiple losses. Extensive experiments serve to underscore the effectiveness of our model. This work contributes significantly to the ongoing exploration of cell subpopulations and tumor microenvironments, and the code of our work will be public at https://github.com/DayuHuu/scEMC.

Injectable, thermo-sensitive and self-adhesive supramolecular hydrogels built from binary herbal small molecules towards reusable antibacterial coatings.

Herbal hydrogels as a new class of sustainable functional materials have attracted extensive attention. However, the development of herbal hydrogels is significantly hindered due to their poor hydrogel performances and the lack of universal preparation methods. In this study, four herbal hydrogels composed of phytochemical polyphenols and stevioside compounds are prepared through a facile heating-cooling process, where multiple hydrogen bonding interactions between two monomers provide the main driving force for gelation. These herbal hydrogels exhibit thermo-sensitivity and good reversibility (25-90 °C), robust adhesion behaviours on hydrophilic and hydrophobic surfaces (maximum adhesion strength of 591.7 kPa), and outstanding antibacterial properties (100% bacteriostatic ratio). Profiting from these intriguing characteristics, they are demonstrated to show great potential as natural antibacterial coatings by depositing thin hydrogel layers onto diverse substrates. More importantly, the hydrogel coatings could be easily recycled by thermal regelation and reused at least 5 times. This work proposes a simple and universal strategy for preparing functional hydrogels based on binary herbal small molecules, which also sheds light on the development of reusable hydrogel coatings.

Subgraph Propagation and Contrastive Calibration for Incomplete Multiview Data Clustering.

The success of multiview raw data mining relies on the integrity of attributes. However, each view faces various noises and collection failures, which leads to a condition that attributes are only partially available. To make matters worse, the attributes in multiview raw data are composed of multiple forms, which makes it more difficult to explore the structure of the data especially in multiview clustering task. Due to the missing data in some views, the clustering task on incomplete multiview data confronts the following challenges, namely: 1) mining the topology of missing data in multiview is an urgent problem to be solved; 2) most approaches do not calibrate the complemented representations with common information of multiple views; and 3) we discover that the cluster distributions obtained from incomplete views have a cluster distribution unaligned problem (CDUP) in the latent space. To solve the above issues, we propose a deep clustering framework based on subgraph propagation and contrastive calibration (SPCC) for incomplete multiview raw data. First, the global structural graph is reconstructed by propagating the subgraphs generated by the complete data of each view. Then, the missing views are completed and calibrated under the guidance of the global structural graph and contrast learning between views. In the latent space, we assume that different views have a common cluster representation in the same dimension. However, in the unsupervised condition, the fact that the cluster distributions of different views do not correspond affects the information completion process to use information from other views. Finally, the complemented cluster distributions for different views are aligned by contrastive learning (CL), thus solving the CDUP in the latent space. Our method achieves advanced performance on six benchmarks, which validates the effectiveness and superiority of our SPCC.

Transcranial Magnetic Stimulation as a Therapy for Migraine: An Overview of Systematic Reviews.

Introduction: This overview of systematic reviews (SRs) systematically collected, evaluated, and combined the evidence for migraine treatment with transcranial magnetic stimulation (TMS). Methods: We conducted a systematic literature search in various databases, such as PubMed, The Cochrane Library, Web of Science, Embase, the China National Knowledge Infrastructure, Wanfang, VIP, and China Biomedical Literature. Two reviewers independently assessed the methodological quality, risk of bias, reporting quality, and strength of evidence of the included studies using AMSTAR-2, ROBIS, the PRISMA checklist, and the GRADE system. Results: We performed an overview of 7 relevant SRs, of which 4 were of moderate quality and 3 were of low quality according to AMSTAR 2. All SRs had low risk of bias in Phase 1 (Assessing relevance), Domain 1 (Study eligibility criteria), and Domain 4 (Synthesis and findings) as evaluated by ROBIS. In Domain 2 (Identification and selection of studies), 4 SRs (57.1%) had low risk of bias, while in Domain 3 (data collection and study appraisal) and Risk of Bias in the Review Phase 3, 4 SRs (57.1%) had low risk of bias. The PRISMA reporting standards were generally comprehensive, but some limitations were observed in the assessments, pooled results, evidence reliability, registration and protocols, and funding sources. The GRADE levels ranged from moderate to low, with 10 outcomes of moderate quality and 6 outcomes of low quality. The main reason for the low quality of evidence was the small sample size and high heterogeneity of the available studies. Conclusion: TMS may improve migraine severity and frequency, but the evidence is limited due to methodological flaws and heterogeneity. Future studies should standardize use, assess side effects, and compare with other treatments.

Iterative Deep Structural Graph Contrast Clustering for Multiview Raw Data.

Multiview clustering has attracted increasing attention to automatically divide instances into various groups without manual annotations. Traditional shadow methods discover the internal structure of data, while deep multiview clustering (DMVC) utilizes neural networks with clustering-friendly data embeddings. Although both of them achieve impressive performance in practical applications, we find that the former heavily relies on the quality of raw features, while the latter ignores the structure information of data. To address the above issue, we propose a novel method termed iterative deep structural graph contrast clustering (IDSGCC) for multiview raw data consisting of topology learning (TL), representation learning (RL), and graph structure contrastive learning to achieve better performance. The TL module aims to obtain a structured global graph with constraint structural information and then guides the RL to preserve the structural information. In the RL module, graph convolutional network (GCN) takes the global structural graph and raw features as inputs to aggregate the samples of the same cluster and keep the samples of different clusters away. Unlike previous methods performing contrastive learning at the representation level of the samples, in the graph contrastive learning module, we conduct contrastive learning at the graph structure level by imposing a regularization term on the similarity matrix. The credible neighbors of the samples are constructed as positive pairs through the credible graph, and other samples are constructed as negative pairs. The three modules promote each other and finally obtain clustering-friendly embedding. Also, we set up an iterative update mechanism to update the topology to obtain a more credible topology. Impressive clustering results are obtained through the iterative mechanism. Comparative experiments on eight multiview datasets show that our model outperforms the state-of-the-art traditional and deep clustering competitors.

Herbal molecule-mediated dual network hydrogels with adhesive and antibacterial properties for strain and pressure sensing.

Multifunctional integration is the focus of hydrogel-based flexible sensors, and formation of a dual network (DN) could shed light on the fabrication of hydrogels with multifunctionality and enhanced properties. In this study, a DN hydrogel was fabricated by the self-assembly of herbal molecule glycyrrhizic acid (GA) as the first hydrogel network and subsequent photocrosslinking of methacrylated sodium alginate (SA-MA) to form the second network. Profiting from the good compatibility between the two hydrogel networks, the obtained DN hydrogels with a homogeneous porous microstructure were endowed with remarkably enlarged stretching (114.5%) and compression (74.4%) strains. In addition, they were demonstrated to display excellent bacteriostatic activity (>99.9%) against Escherichia coli and Staphylococcus aureus owing to the synergetic antibacterial effect of GA and SA-MA. The DN hydrogels as strain sensors possessed high sensitivity (GF = 1.39), linear sensing (R 2 > 0.99), rapid response (180 ms), and good stability (1300 times) for human motion detection. Besides, the DN hydrogels could also be used to conduct pressure sensing such as application of heavy weights and even human pulses. All results suggest that the developed DN hydrogels have great potential in serving as epidermal and implantable flexible sensors for human health monitoring.

2-Bromopalmitate decreases spinal inflammation and attenuates oxaliplatin-induced neuropathic pain via reducing Drp1-mediated mitochondrial dysfunction.

Oxaliplatin (OXA) is a third-generation platinum compound with clinical activity in multiple solid tumors. Due to the repetition of chemotherapy cycle, OXA-induced chronic neuropathy presenting as paresthesia and pain. This study explored the neuropathy of chemotherapy pain and investigated the analgesic effect of 2-bromopalmitate (2-BP) on the pain behavior of OXA-induced rats. The chemotherapy pain rat model was established by the five consecutive administration of OXA (intraperitoneal, 4 mg/kg). After the establishment of OXA-induced rats, the pain behavior test, inflammatory signal analysis and mitochondrial function measurement were conducted. OXA-induced rats exhibited mechanical allodynia and spinal inflammatory infiltration. Our fluorescence and western blot analysis revealed spinal astrocytes were activated in OXA rats with up-regulation of astrocytic markers. In addition, NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome mediated inflammatory signal cascade was also activated. Inflammation was triggered by dysfunctional mitochondria which represented by increase in cyclooxygenase-2 (COX-2) level and manganese superoxide dismutase (Mn-SOD) activity. Intrathecally injection of 2-BP significantly attenuated dynamin-related protein 1 (Drp1) mediated mitochondrial fission, recovered mitochondrial function, suppressed NLRP3 inflammasome cascade, and consequently decreased mechanical pain sensitivity. For cell research, 2-BP treatment significantly reversed tumor necrosis factor-α (TNF-α) induced mitochondria membrane potential deficiency and high reactive oxygen species (ROS) level. These findings indicate 2-BP decreases spinal inflammation and relieves OXA-induced neuropathic pain via reducing Drp1-mediated mitochondrial dysfunction.

Resveratrol ameliorates oxaliplatin-induced neuropathic pain via anti-inflammatory effects in rats.

Oxaliplatin (OXA) is a common chemotherapy drug and exhibits clinical activity in several cancer types. Its anticancer clinical effect is frequently accompanied by neurotoxicity. The symptoms include paresthesia and pain, which adversely affect the quality of life of patients. In the present study, five consecutive intraperitoneal injections of 4 mg/kg OXA were used to mimic chemotherapy in rats. OXA administration induced mechanical allodynia, activated spinal astrocytes and triggered the inflammatory response. To explore potential therapeutic options for OXA-induced neuropathic pain, resveratrol (Res) was intrathecally injected into the spinal cord of OXA-treated rats. Paw withdrawal threshold values of OXA-treated rats were increased, indicating an antinociception effect of Res on OXA-induced pain. Additionally, Res treatment reduced the levels of glial fibrillary acidic protein, TNF-α, IL-1ß and NF-κB, which were upregulated in OXA-treated rats (compared with control). Furthermore, Auto Dock data showed that Res binds to cyclooxygenase-2 (COX-2) through six hydrogen bonds. Western blot analysis and reactive oxygen species (ROS) assays indicated that Res treatment decreased COX-2 expression and suppressed ROS production. In summary, intrathecal injection of Res reduced the spinal COX-2-mediated ROS generation and inflammatory reaction, suppressed astrocytic activation, and alleviated OXA-induced neuropathic pain.

Effectiveness of herb-partitioned moxibustion on the navel for pregnancy outcomes in patients with recurrent implantation failure undergoing in vitro fertilization and embryo transfer: a study protocol for a randomized controlled trial.

BACKGROUND: Recurrent implantation failure (RIF) in the majority of patients undergoing in vitro fertilization and embryo transfer (IVF-ET) is caused by various factors such as maternal age, embryo quality, endometrial receptivity (ER), and immunity. The incidence of RIF is usually between 5 and 10%. Previous studies have shown that herb-partitioned moxibustion on the navel is one of the treatment methods of acupuncture with a positive effect on pregnancy. However, its application in the treatment of RIF has not been reported. Therefore, this study aims to evaluate the effectiveness and safeness of herb-partitioned moxibustion on the navel in improving the outcome of frozen embryo transfer (FET) in patients with RIF. METHODS: This study conducts a randomized controlled trial (RCT). It is planned to recruit 210 patients undergoing RIF for FET from Affiliated Hospital of Shandong University of Traditional Chinese Medicine and randomly divide them into the treatment group and the control group in a ratio of 1:1. The patient of the treatment group will be treated with herb-partitioned moxibustion on the navel once a week for three consecutive menstrual cycles. No intervention will be used in the control group for 3 menstrual cycles. In the fourth menstrual cycle, all patients will undergo artificial cycle to prepare the endometrium for FET. The pregnancy outcomes will be recorded after a 3-month follow-up. Primary outcome will be assessed as the ongoing pregnancy rate compared with the control group. Secondary outcomes include the endometrial type, resistance index (RI), pulsatility index (PI) of the bilateral uterine artery, endometrial blood flow, serum estradiol (E2), progesterone (P), biochemical pregnancy rate, implantation rate, and clinical pregnancy rate. DISCUSSION: If the results show that the herb-partitioned moxibustion on the navel can improve IVF-ET outcomes in patients with RIF, it will be recommended in clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) ChiCTR2100043954 . Registered on 8 July 2021.

Acupuncture for nasal congestion in COVID-19: A protocol for systematic review and meta-analysis.

BACKGROUND: From the end of 2019 to now, coronavirus disease 2019 (COVID-19) has put enormous strain on the world's health systems, causing significant deaths and economic losses worldwide. Nasal congestion, one of the symptoms of COVID-19, poses considerable problems for patients. In China, acupuncture has been widely used to treat nasal congestion caused by COVID-19, but there is still a lack of evidence-based medical evaluation. METHODS: According to the retrieval strategies, randomized controlled trials on the acupuncture for COVID-19 nasal congestion were obtained from China National Knowledge Infrastructure, WanFang, VIP, PubMed, Embase, and Cochrane Library, regardless of publication date, or language. Studies were screened based on inclusion and exclusion criteria, and the Cochrane risk bias assessment tool was used to evaluate the quality of the studies. The meta-analysis was performed using Review Manager (RevMan 5.3) and STATA 14.2 software. Ultimately, the evidentiary grade for the results will be evaluated. RESULTS: The study will provide a high-quality and convincing assessment of the efficacy and safety of acupuncture in the treatment of COVID-19's nasal congestion and will be published in peer-reviewed journals. CONCLUSION: Our findings will provide references for future clinical decision and guidance development. PROSPERO REGISTRATION NUMBER: NO.CRD42021299482.

Moxibustion for abdominal pain in COVID-19: A protocol for systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease that makes breathing difficult and is often accompanied by abdominal pain and distension. Moxibustion, a special external treatment of traditional Chinese medicine, has shown beneficial effects in the treatment of abdominal pain. Currently, there is a lack of systematic reviews on moxibustion for the treatment of abdominal pain. We conduct this study to evaluate the efficacy and safety of moxibustion in the treatment of abdominal pain. This study is designed to evaluate the effectiveness and safety of moxibustion for abdominal pain in COVID-19. METHODS: Randomized controlled trials from December 2019 to December 2021 will be included, without restrictions on language or publication date. PubMed, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Databases, China National Knowledge Infrastructure, Wanfang Database, and VIP Database were searched. Two researchers will independently select studies, extract data, and evaluate study quality. The Cochrane risk of bias tool for randomized trials will be used to assess the risk of bias in the included studies. Statistical analyses will be conducted using the RevMan 5.3 software. RESULTS: This study aimed to prove the efficacy and safety of moxibustion for abdominal pain in patients with COVID-19. Our study provides a more accurate treatment method for abdominal pain during COVID-19. We will publish our results in a peer-reviewed journal. CONCLUSION: This study will provide more convincing evidence for clinicians to treat these conditions and help them make appropriate decisions. ETHICS AND DISSEMINATION: This study did not include personal information. Ethical approval was not required for this study. INPLASY REGISTRATION NUMBER: INPLASY2021120104.

Association of polymorphisms in ADAMTS-5 gene with the susceptibility to knee osteoarthritis: A protocol for systematic review and meta-analysis.

BACKGROUND: To systematically review literature evidence to discover the association of ADAMTS5 (A Disintegrin And Metalloproteinase with Thrombospondin-like motifs 5) gene polymorphisms and the risk of developing KOA (knee osteoarthritis). METHODS: We systematically searched the related randomized controlled trials in 4 databases from inception to August 2021, including the Embase, Web of Science, PubMed, and CNKI (Chinese National Knowledge Infrastructure) databases. No language and publication status restrictions. Two reviewers will independently screen all included studies, and the meta-analysis will be conducted using the Review Manager (RevMan 5.3, Cochrane Collaboration, Nordic Cochrane Center, Copenhagen, Denmark). RESULTS: The gathered evidence suggests that there may be a close relationship between the SNP in the ADAMTS5 gene and KOA development. This study will provide a high-quality and convincing evaluation of the treatment of KOA from the consideration of ADAMTS5 gene and will be published in a peer-reviewed journal. CONCLUSION: ADAMTS5 polymorphism is likely an important risk factor for the development of KOA. Our study will provide a more accurate treatment method for the treatment of KOA. TRIAL REGISTRATION NUMBER: CRD42021276317.

Long-term ketamine administration induces bladder damage and upregulates autophagy-associated proteins in bladder smooth muscle tissue.

Long-term ketamine abuse can cause significant lower urinary tract symptoms in humans, termed ketamine-associated cystitis (KC). Here, we established a model of long-term (6 months) ketamine administration in wild-type (C57BL/6) mice. We elucidated the pathological effects of ketamine in the bladder and investigated changes in autophagy-associated protein expression (i.e., LC3, Beclin-1, and P62) and inflammatory cytokines (i.e., IL-6 and IL-1ß) in the bladder smooth muscle tissue. Long-term ketamine administration reduced the number of layers in the bladder mucosal epithelial cells (4-5 layers in the saline group vs. 2-3 layers in the ketamine groups), but increased the number of mast cells and collagen fibers. LC3-II/LC3-I, Beclin-1, IL-6, and IL-1ß protein expression in the bladder smooth muscle tissues of ketamine-treated mice was significantly increased. The mRNA and protein levels of P62 in the Ket-60 mg/kg group were also significantly increased, but not the Ket-30 mg/kg group. Our results reveal that long-term ketamine administration can cause cystitis-like pathological changes in mice, and the disordered autophagy in the bladder tissue may be involved in the persistent bladder damage following long-term administration of ketamine at 60 mg/kg.

Effects of herb-partitioned moxibustion for ulcerative colitis: A protocol for systematic review and meta-analysis.

BACKGROUND: Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disease of the colonic mucosa. Herb-partitioned moxibustion (HPM) treatment has been demonstrated to be effective in the treatment of UC. However, there is still a lack of high-quality evidence to support the effectiveness and safety of HPM on patients with UC. This study will aim to systematically explore the efficacy of HPM for the treatment of UC. METHODS: We will search the electronic databases of Embase, MEDLINE, PubMed, Cochrane Library Central Register of Controlled Trials, China national knowledge infrastructure database (CNKI), Wan fang database, Chongqing VIP information, and SinoMed from their inception to June 2020. Randomized controlled trials (RCTs) of HPM for the treatment of UC will be included. RevMan 5.3 software (The Nordic Cochrane Center, The Cochrane Collaboration, Copenhagen, Denmark) will be applied for statistical analysis. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: The conclusion of our systematic review will provide more appropriate evidence-based decisions to assist clinicians during the decision-making process when dealing with UC.

Effects of herb-partitioned moxibustion for primary dysmenorrhea: A protocol for systematic review and meta-analysis.

BACKGROUND: Primary dysmenorrhea (PD) is a cyclic cramp in pelvic which affects the quality of life. Herb-partitioned moxibustion (HPM), a critical component of moxibustion therapy in traditional Chinese medicine, has been used to treat PD. However, there is still a lack of high-quality evidence to support the effectiveness and safety of HPM on patients with PD. The object of this work is to evaluate the efficacy and safety of HPM in the management of PD. METHODS: The Embase, MEDLINE, PubMed, Cochrane Library Central Register of Controlled Trials, China national knowledge infrastructure database, Wan fang database, Chongqing VIP information, and SinoMed will be searched from their inception to Jun 2020. All randomized controlled trials of HPM for the treatment of PD will be included. We will operate article retrieval, duplication removing, screening, quality evaluation, and data analyses by RevMan 5.3 (The Cochrane Collaboration, Oxford, England). RESULTS: This study will provide a high-quality comprehensive evaluation of the efficacy and safety of HPM for the treatment of PD. CONCLUSION: The conclusion of our systematic review will give more convincing evidence to assist clinicians during the decision-making process when dealing with PD. TRIAL REGISTRATION NUMBER: 10.17605/OSF.IO/UFKNP.

Long-term ketamine administration causes Tau protein phosphorylation and Tau protein-dependent AMPA receptor reduction in the hippocampus of mice.

As a recreational drug of abuse and an injectable anesthetic, ketamine has been shown to cause cognitive dysfunction and induce psychotic states. Although the specific mechanism is still unclear, it may be linked to synaptic receptors, including the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor. Recent evidence suggests that Tau protein phosphorylation and targeted delivery to the postsynaptic area is involved in maintaining neuronal plasticity, indicating that the neurotoxicity induced by ketamine may be related to the transfer of Tau protein after phosphorylation. In this study, we established a model of long-term (6 months) ketamine administration in wild-type (C57BL/6) and Tau knockout mice to investigate the effects of different doses of ketamine administration on Tau protein expression and phosphorylation in the mouse hippocampus. We also investigated changes in AMPA receptor expression in the synaptic membrane of wild-type and Tau knockout mice. Our results showed that long-term ketamine administration led to excessive Tau protein phosphorylation at Ser202/Thr205 and Ser396, but not at Ser199, Ser262 and Ser404. Most importantly, long-term ketamine administration decreased AMPA receptor levels in the hippocampal cell membrane in a Tau protein-dependent manner. Our results reveal the role of Tau protein phosphorylation in the mechanism of ketamine neurotoxicity, suggesting that the changes of membrane AMPA receptor and synaptic function induced by ketamine are mediated by abnormal phosphorylation of Tau protein at specific sites.

A fatal case of hypothermia caused by dog bites.

Death from hypothermia usually *We presented a fatal case of hypothermia after being bitten by dog in this article. occurs among people exposed to cold and humid environmental conditions when they are homeless, aged, suffering from natural or psychiatric diseases and drug or alcohol intoxication. A normal healthy person dying from hypothermia due to dog bites is unusual and rare. Here, we present a fatal case of hypothermia following dog bites causing blood loss and multiple wounds on the body. A 56-year-old man was found dead in a remote roadside puddle of a small village, early in the morning. He was naked, and his body trunk and limbs had multiple irregular wounds. Gray animal hairs could be seen in parts of the wound cavities and surrounding areas. In addition, there was a kennel near the scene. Family members argued that the deceased was bitten to death by a dog. However, autopsy revealed several findings which were strongly supportive of fatal hypothermia. Moreover, we saw no obvious changes caused by blood loss, either on the body surface or internal organs. Accordingly, we concluded the true cause of his death was fatal hypothermia; bites from a dog was a necessary causative factor.

Effects of Ketamine on Levels of Inflammatory Cytokines IL-6, IL-1ß, and TNF-α in the Hippocampus of Mice Following Acute or Chronic Administration.

Ketamine is an injectable anesthetic and recreational drug of abuse commonly used worldwide. Many experimental studies have shown that ketamine can impair cognitive function and induce psychotic states. Neuroinflammation has been suggested to play an important role in neurodegeneration. Meanwhile, ketamine has been shown to modulate the levels of inflammatory cytokines. We hypothesized that the effects of ketamine on the central nervous system are associated with inflammatory cytokines. Therefore, we set out to establish acute and chronic ketamine administration models in C57BL/6 mice, to evaluate spatial recognition memory and emotional response, to analyze the changes in the levels of the inflammatory cytokines interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) in the mouse hippocampus, employing behavioral tests, Western blot, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and immunohistochemistry. Our results showed that ketamine at the dose of 60 mg/kg induced spatial recognition memory deficit and reduced anxiety-like behaviors in mice after chronic administration. Moreover, we found that ketamine increased the hippocampal levels of IL-6 and IL-1ß after single, multiple and long-term administration in a dose-dependent manner. However, the expression level of TNF-α differed in the mouse hippocampus under different conditions. Single administration of ketamine increased the level of TNF-α, whereas multiple and long-term administration decreased it significantly. We considered that TNF-α expression could be controlled by a bi-directional regulatory pathway, which was associated with the dose and duration of ketamine administration. Our results suggest that the alterations in the levels of inflammatory cytokines IL-6, IL-1ß, and TNF-α may be involved in the neurotoxicity of ketamine.