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Abstract Substance use disorders (SUDs) imposes profound physical, psychological, and socioeconomic burdens on individuals, families, communities, and society as a whole, but the available treatment options remain limited. Deep brain-machine interfaces (DBMIs) provide an innovative approach by facilitating efficient interactions between external devices and deep brain structures, thereby enabling the meticulous monitoring and precise modulation of neural activity in these regions. This pioneering paradigm holds significant promise for revolutionizing the treatment landscape of addictive disorders. In this review, we carefully examine the potential of closed-loop DBMIs for addressing SUDs, with a specific emphasis on three fundamental aspects: addictive behaviors-related biomarkers, neuromodulation techniques, and control policies. Although direct empirical evidence is still somewhat limited, rapid advancements in cutting-edge technologies such as electrophysiological and neurochemical recordings, deep brain stimulation, optogenetics, microfluidics, and control theory offer fertile ground for exploring the transformative potential of closed-loop DBMIs for ameliorating symptoms and enhancing the overall well-being of individuals struggling with SUDs.

A three-dimensional elastic–plastic finite element model of a six-roll cold rolling mill has been developed using the finite element software ABAQUS. The actual parameters of the rolling mill have been incorporated into the finite element model, with the working conditions applied as boundary constraints and load conditions. Subsequently, a non-symmetrical bending force is introduced to the finite element model. Through simulation calculations, this study analyzes the patterns of change in the transverse pressure of the rolling mill and roller pressure during non-symmetrical bending, as well as the variations in strip thickness, crown, edge drop, and flatness. Additionally, the regulating function of the bending force is examined. Each adjustment of 5 t in the asymmetric bending force results in an increase of approximately 0.01 mm in the thickness of the positive bending side of the strip while causing a decrease of about 0.01 mm in the thickness of the negative bending side. Therefore, the application of asymmetric bending forces proves to be effective in controlling the shape of lateral wave defects on the edges of steel strips.

Stroke, a cerebrovascular disease with a high mortality rate, is categorized as either ischemic or hemorrhagic. Current existing therapies have limitations, including a narrow time window for treatment. As stroke induces a rapid and large immune response, immune cells and inflammatory mediators have become promising therapeutic targets for both ischemic and hemorrhagic strokes. In recent years, T cells have been investigated for their role in the pathogenesis of secondary injury and their therapeutic potential after stroke. And regulatory T cells, as one of the subpopulations of T cells, have been proved neuroprotective at both acute and recovery stages. In this review, we summarize the existing roles of Tregs in stroke and the various methods available for Treg intervention, and then provide a perspective for the future of immunotherapy in stroke.

Summary: Background: Patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) present intestinal disturbances. Recent epidemiological data have showed that, worldwide, over half of newly diagnosed T1D patients were adults. However, the gut microbial alterations in adult-onset T1D are unclear. We aimed to identify the signatures of gut microbiota and metabolites in patients with adult-onset T1D systematically, comparing with T2D patients and healthy controls (HCs). Methods: This study enrolled 218 subjects from February 2019 to April 2022 (discovery cohort: 36 HCs, 51 patients with adult-onset T1D and 56 patients with T2D; validation cohort: 28 HCs, 27 patients with adult-onset T1D and 20 patients with T2D). Gut microbial profiles of the study subjects were investigated by metagenomic sequencing, and their faecal and serum metabolites were measured with targeted metabolomics. The study was registered on ClinicalTrials.gov (NCT05252728). Findings: Patients with adult-onset T1D had significant differences in the composition of bacteria and their metabolites, characterized by notable depletion of short-chain fatty acid-producing bacteria, especially Eubacterium rectale. This was associated with a severe loss of phenolic acids and their derivatives, including gallic acid (associated with glucose metabolism) and 3,4-dihydroxyhydrocinnamic acid (linked with glucose metabolism and pancreatic beta cell autoimmunity). A predictive model based on six bacteria and six metabolites simultaneously discriminated adult-onset T1D from T2D and HCs with high accuracy. Interestingly, bacterial-viral or bacterial-fungal trans-kingdom relationships, especially positive correlations between bacteriophages and beneficial bacteria, were significantly reduced in adult-onset T1D compared to HCs. Interpretation: Adult-onset T1D patients exhibit unique changes in host-microbiota-metabolite interactions. Gut microbiota and metabolite-based algorithms could be used as additional tools for differential diagnosis of different types of diabetes and beyond. Funding: National Key Research and Development Program of China, the National Natural Science Foundation of China.

Summary: Glioblastoma (GBM) is the most common form of malignant primary brain tumor with a dismal prognosis. Currently, the standard treatments for GBM rarely achieve satisfactory results, which means that current treatments are not individualized and precise enough. In this study, a multiomics-based GBM classification was established and three subclasses (GPA, GPB, and GPC) were identified, which have different molecular features both in bulk samples and at single-cell resolution. A robust GBM poor prognostic signature (GPS) score model was then developed using machine learning method, manifesting an excellent ability to predict the survival of GBM. NVP−BEZ235, GDC−0980, dasatinib and XL765 were ultimately identified to have subclass-specific efficacy targeting patients with a high risk of poor prognosis. Furthermore, the GBM classification and GPS score model could be considered as potential biomarkers for immunotherapy response. In summary, an integrative genomic analysis was conducted to advance individual-based therapies in GBM.

The 17th National Annual Conference on Neurological Infectious Diseases and Cerebrospinal Fluid Cytology of the Chinese Medical Association Neurology Branch was successfully held in Wuhan, Hubei, China. During the conference, many well-known neurology experts in China conducted in-depth and detailed discussions on the research progress of infectious diseases of the nervous system and cerebrospinal fluid cytology, which benefited the participants a lot.

Minimally invasive surgery has been widely used in the treatment of patients with intracerebral hemorrhage in recent years, and has achieved good clinical efficacy. Based on the basic theory of minimally invasive surgery, indications and contraindications are discussed, and then the minimally invasive preoperative preparation, intraoperative operation, postoperative management, and other aspects are systematically discussed. Finally, the application of microsurgery in the precise treatment of intracerebral hemorrhage is further prospected.

Background and AimsRecent studies have shown that artificial intelligence-based computer-aided detection systems possess great potential in reducing the heterogeneous performance of doctors during endoscopy. However, most existing studies are based on high-quality static images available in open-source databases with relatively small data volumes, and, hence, are not applicable for routine clinical practice. This research aims to integrate multiple deep learning algorithms and develop a system (DeFrame) that can be used to accurately detect intestinal polyps in real time during clinical endoscopy.MethodsA total of 681 colonoscopy videos were collected for retrospective analysis at Xiangya Hospital of Central South University from June 2019 to June 2020. To train the machine learning (ML)-based system, 6,833 images were extracted from 48 collected videos, and 1,544 images were collected from public datasets. The DeFrame system was further validated with two datasets, consisting of 24,486 images extracted from 176 collected videos and 12,283 images extracted from 259 collected videos. The remaining 198 collected full-length videos were used for the final test of the system. The measurement metrics were sensitivity and specificity in validation dataset 1, precision, recall and F1 score in validation dataset 2, and the overall performance when tested in the complete video perspective.ResultsA sensitivity and specificity of 79.54 and 95.83%, respectively, was obtained for the DeFrame system for detecting intestinal polyps. The recall and precision of the system for polyp detection were determined to be 95.43 and 92.12%, respectively. When tested using full colonoscopy videos, the system achieved a recall of 100% and precision of 80.80%.ConclusionWe have developed a fast, accurate, and reliable DeFrame system for detecting polyps, which, to some extent, is feasible for use in routine clinical practice.

Objective: The main aims of the study were to explore the correlation between different times of a minimally invasive operation and perihaematomal oedema properties in patients with cerebral hemorrhage, to identify the optimal time window for a minimally invasive operation and to observe the effect of different doses of urokinase on perihaematomal oedema properties. Methods: A retrospective analysis was performed on 95 patients with cerebral hemorrhage who were treated in the Department of Neurology at the Tianmen First People’s Hospital between April 2014 and December 2017. Finally, 66 valid cases were included, and they were divided into three groups according to the time from onset to the minimally invasive operation. Haematoma volume and oedema volume before the surgery, 4 days after the surgery and 14 days after the surgery were compared among the three groups. Results: There was no significant difference in postoperative oedema volume among the three groups. The difference in haematoma volume among the three groups may be related to haematoma absorption after a long period of time. There was no significant linear correlation between the timing of surgery and the dosage of urokinase or the perihaematomal oedema volume in the three groups. There was no significant difference in the rebleeding rate and pulmonary infection complication rate among the three groups. Conclusions: The operation timing of minimally invasive puncture haematoma removal in patients with cerebral hemorrhage has no obvious influence on perihaematomal oedema, rebleeding and pulmonary infection complications. This study has limitations, and a prospective cohort study with a larger sample size is needed to explore the details, such as patient selection and the timing of minimally invasive surgery.

Stroke is the second leading cause of death worldwide. Therefore, research on prevention and treatment for stroke has great significance. In recent years, the development of artificial intelligence (AI) technology has brought new hopes to healthcare. The resulting partnerships between clinicians and computation science scientists, supported by growing strength of clinical informatics, are beginning to yield positive results. AI techniques have been used successfully in skin/cancer-related studies. Besides that, AI also have been used more and more in the field of stroke. In this review we summarized the application of artificial intelligence in the four main areas of stroke care: diagnosis, outcome prediction, treatment and rehabilitation. Finally, we look forward to the current studies of AI-assisted medical care and make some suggestions for the future potential development direction.

Background and PurposeTo investigate the effect of prior ischemic stroke on the outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19), and to describe the incidence, clinical features, and risk factors of acute ischemic stroke (AIS) following COVID-19.MethodsIn this population-based retrospective study, we included all the hospitalized positive patients with COVID-19 at Wuhan City from December 29, 2019 to April 15, 2020. Clinical data were extracted from administrative datasets coordinated by the Wuhan Health Commission. The propensity score matching and multivariate logistic regression analyses were used to adjust the confounding factors.ResultsThere are 36,358 patients in the final cohort, in which 1,160 (3.2%) had a prior stroke. After adjusting for available baseline characteristics, patients with prior stroke had a higher proportion of severe and critical illness and mortality. We found for the first time that the premorbid modified Rankin Scale (MRS) grouping (odds ratio [OR] = 1.796 [95% CI 1.334–2.435], p < 0.001) and older age (OR = 1.905 [95% CI 1.211–3.046], p = 0.006) imparted increased risk of death. AIS following COVID-19 occurred in 124 (0.34%) cases, and patients with prior stroke had a much higher incidence of AIS (3.4%). Logistic regression analyses confirmed an association between the severity of COVID-19 with the incidence of AIS. COVID-19 patients with AIS had a significantly higher mortality compared with COVID-19 patients without stroke and AIS patients without COVID-19.ConclusionsCoronavirus disease 2019 patients with prior stroke, especially those with the higher premorbid MRS or aged, have worse clinical outcomes. Furthermore, COVID-19 increases the incidence of AIS, and the incidence is positively associated with the severity of COVID-19.

On September 27, 2021, the Safety and Efficacy of Surgical Treatment in Severe Primary Pontine Hemorrhage Evacuation (STIPE) trial kick-off meeting was successfully held. During the online meeting, many member institutions from all over the country had together witnessed the successful launch of this trial. The STIPE trial is expected to support the safety and efficacy of surgical treatment for the patients with severe primary pontine hemorrhage.

Primary brainstem hemorrhage (PBSH) is the most fatal subtype of intracerebral hemorrhage and is invariably associated with poor prognosis. Several prognostic factors are involved, of which the two most predominant and consistent are the initial level of consciousness and hemorrhage size. Other predictors, such as age, hyperthermia, and hydrocephalus, are generally not dependable indicators for making prognoses. Scoring systems have now been developed that can predict mortality and functional outcomes in patients suffering from PBSH, which can thus guide treatment decision-making. A novel grading scale, entitled “the new primary pontine hemorrhage (PPH) score,” represents the latest approach in scoring systems. In this system, patients with a score of 2–3 points appear to benefit from surgical management, although this claim requires further verification. The four main surgical options for the treatment of PBSH are craniotomy, stereotactic hematoma puncture and drainage, endoscopic hematoma removal, and external ventricular drainage. Nevertheless, the management of PBSH still primarily involves conservative treatment methods and surgery is generally not recommended, according to current practice. However, the ongoing clinical trial, entitled Safety and Efficacy of Surgical Treatment in Severe Primary Pontine Hemorrhage Evacuation (STIPE), should provide additional evidence to support the surgical treatment of PBSH. Therefore, we advocate the update of epidemiological data and re-evaluation of PBSH treatment in a contemporary context.

In November 2021, the project of “Multi-sensor fusion and intelligent aspiration control of minimally invasive surgical robot for intracerebral hemorrhage” has been successfully supported by the National Natural Science Foundation of China (NSFC). Professor Zhouping Tang, a neurologist from Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology in Wuhan China will lead this project of ¥2,400,000 in the next four years. Team led by Professor Zhouping Tang will work with team led by Professor Bo Tao from School of Mechanical Science & Engineering, Huazhong University of Science and Technology, team led by Professor Dansheng Chen from School of Mechanical Engineering & Automation-BUAA, Beihang University and team led by engineer Wenjie Liu from Beijing WanTeFu Medical Instrument Co., Ltd to carry out fundamental investigations of micro-invasive treatment using Coexisting-Cooperative-Cognitive Robots (Tri-Co Robots).

Since mass effect and secondary brain injuries persist in the pathogenesis of intracerebral hemorrhage, hematoma evacuation within a limited time is reasonable. However, it is complex to define an accurate therapeutic time window (TTW) for hematoma evacuation. In this review, studies about TTW were discussed from four aspects: histopathology, molecular pathophysiology, neuroimaging and clinical outcomes. Animal experiments indicated that 6–12 h is the pathophysiological TTW of minimally invasive surgery. Clinical trials suggested that there is a correlation between TTW and clinical outcomes, while the exact TTW is still unclear due to lack of sufficient clinical studies, which deserves further investigation.

Infectious diseases have always been a major threat to the survival of humanity. Additionally, they bring an enormous economic burden to society. The conventional methods for bacteria identification are expensive, time-consuming and laborious. Therefore, it is of great importance to automatically rapidly identify pathogenic bacteria in a short time. Here, we constructed an AI-assisted system for automating rapid bacteria genus identification, combining the hyperspectral microscopic technology and a deep-learning-based algorithm Buffer Net. After being trained and validated in the self-built dataset, which consists of 11 genera with over 130,000 hyperspectral images, the accuracy of the algorithm could achieve 94.9%, which outperformed 1D-CNN, 2D-CNN and 3D-ResNet. The AI-assisted system we developed has great potential in assisting clinicians in identifying pathogenic bacteria at the single-cell level with high accuracy in a cheap, rapid and automatic way. Since the AI-assisted system can identify the pathogenic genus rapidly (about 30 s per hyperspectral microscopic image) at the single-cell level, it can shorten the time or even eliminate the demand for cultivating. Additionally, the system is user-friendly for novices.

NCyborg Project, a new stroke rehabilitation pattern based on brain computer interface (BCI) and brain-inspired intelligent robots, is set up by Tongji Hospital and BrainCo. We will briefly introduce this project in this paper.

Combination with genomic DNA is one of the important ways for microRNAs (miRNAs) to perform biological processes. However, because of lack of an experimental method, the identified genomic sites targeted by microRNA were only located in the promoter and enhancer regions. In this study, based on affinity purification of labeled biotin at the 3′-end of miRNAs, we established an efficiently experimental method to screen miRNA binding sequences in the whole genomic regions in vivo. Biotinylated miR-373 was used to test our approach in MCF-7 cells, and then Sanger and next-generation sequencing were used to screen miR-373 binding sequences. Our results demonstrated that the genomic fragments precipitated by miR-373 were located not only in promoter but also in intron, exon, and intergenic. Eleven potentially miR-373 targeting genes were selected for further study, and all of these genes were significantly regulated by miR-373. Furthermore, the targeting sequences located in E-cadherin, cold-shock domain-containing protein C2 (CSDC2), and PDE4D genes could interact with miR-373 in MCF-7 cells rather than HeLa cells, which is consistent with our data that these three genes can be regulated by miR-373 in MCF-7 cells while not in HeLa cells. On the whole, this is an efficient method to identify miRNA targeting sequences in the whole genome.

Stem cell therapy has emerged as a new promising therapeutic strategy for intracerebral hemorrhage (ICH). However, the efficiency of stem cell therapy is partially limited by low retention and engraftment of the delivered cells. Therefore, it’s necessary to improve the migration ability of stem cells to the injured area in order to save the costs and duration of cell preparation. This study aimed to investigate whether overexpression of CX3CR1, the specific receptor of chemokine fractalkine (FKN), in adipose-derived stem cells (ADSCs) can stimulate the cell migration to the injured area in the brain, improve functional recovery and protect against cell death following experimental ICH. ADSCs were isolated from subcutaneous adipose tissues of rats. ICH was induced by means of an injection of collagenase type VII. ELISA showed that the expression levels of fractalkine/FKN were increased at early time points, with a peak at day 3 after ICH. And it was found that different passages of ADSCs could express the chemokine receptor CX3CR1. Besides, the chemotactic movements of ADSCs toward fractalkine have been verified by transwell migration assay. ADSCs overexpressing CX3CR1 were established through lentivirus transfection. We found that after overexpression of CX3CR1 receptor, the migration ability of ADSCs was increased both in vitro and in vivo. In addition, reduced cell death and improved sensory and motor functions were seen in the mice ICH model. Thus, ADSCs overexpression CX3CR1 might be taken as a promising therapeutic strategy for the treatment of ICH.

Background: Schizophrenia is a severe psychiatric disorder with a high heritability. A single nucleotide polymorphism (SNP) rs1625579 (G/T; T is the common and presumed risk allele) within an intron of miR-137 gene has been recently suggested to contribute to the susceptibility to schizophrenia by a large-scale genome-wide association study (GWAS) in a sample of predominantly European ancestry. However, subsequent genetic association studies in Chinese population yielded inconsistent results. Methods: A meta-analysis reporting the association between rs1625579 and schizophrenia in Chinese population was carried out, pooling 4 eligible case–control studies involving 2847 patients and 3018 controls. Results: This meta-analysis demonstrated a significant association between rs1625579 and schizophrenia under the allele model [T versus G, odds ratio (OR):1.20, 95% confidence interval (CI): 1.06–1.36] and the recessive model (TT versus GT + GG; OR: 1.19; 95% CI: 1.04–1.37). Additionally, a marginal significant association under the additive model (TT versus GG; OR: 1.64; 95% CI: 1.00–2.69) was observed. However, no significant association was observed under the dominant model (TT + GT versus GG; OR: 1.58; 95% CI: 0.97–2.59). Conclusions: This meta-analysis suggested that the SNP rs1625579 in miR-137 gene might be involved in schizophrenia susceptibility in Chinese Han population.

Sugarcane smut is a fungal disease caused by Sporisorium scitamineum, which can cause severe economic losses in sugarcane industry. The infection depends on the mating of bipolar sporida to form a dikaryon and develops into hyphae to penetrate the meristematic tissue of sugarcane. In this study, we set to isolate bacterial strains capable of blocking the fungal mating and evaluate their potential in control of sugarcane smut disease. A bacterial isolate ST4 from rhizosphere displayed potent inhibitory activity against the mating of S. scitamineum bipolar sporida and was selected for further study. Phylogenetic analyses and biochemical characterization showed that the isolate was most similar to Pseudomonas guariconensis. Methanol extracts from minimum and potato dextrose agar (PDA) agar medium, on which strain ST4 has grown, showed strong inhibitory activity on the sexual mating of S. scitamineum sporida, without killing the haploid cells MAT-1 or MAT-2. Further analysis showed that only glucose, but not sucrose, maltose, and fructose, could support strain ST4 to produce antagonistic chemicals. Consistent with the above findings, greenhouse trials showed that addition of 2% glucose to the bacterial inoculum significantly increased the strain ST4 biocontrol efficiency against sugarcane smut disease by 77% than the inoculum without glucose. The results from this study depict a new strategy to screen for biocontrol agents for control and prevention of the sugarcane smut disease.

Neuroglobin is an endogenous neuroprotective protein, but the underlying neuroprotective mechanisms remain to be elucidated. Our previous yeast two-hybrid screening study identified that Dishevelled-1, a key hub protein of Wnt/β-Catenin signaling, is an interaction partner of Neuroglobin. In this study, we further examined the role of Neuroglobin in regulating Dishevelled-1 and the downstream Wnt/β-Catenin and NFκB signaling pathway. We found that Neuroglobin directly interacts with Dishevelled-1 by co-immunoprecipitation, and the two proteins are co-localized in both cytoplasma and nucleus of SK-N-SH cells. Moreover, the ectopic expression of Neuroglobin promotes the degradation of exogenous and endogenous Dishevelled-1 through the proteasomal degradation pathway. Furthermore, our results showed that Neuroglobin significantly inhibits the luciferase activity of Topflash reporter and the expression of β-Catenin mediated by Dishevelled-1 in SK-N-SH cells. In addition, we also documented that Neuroglobin enhances TNF-α-induced NFκB activation via down-regulating Dishevelled-1. Finally, 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assays showed that Neuroglobin is an important neuroprotectant that protects SK-N-SH cells from TNF-α-induced decrease in cell viability. Taken together, these findings demonstrated that Neuroglobin functions as an important modulator of the Wnt/β-Catenin and NFκB signaling pathway through regulating Dishevelled-1.

In the central nervous system (CNS), the myelin sheath ensures efficient interconnection between neurons and contributes to the regulation of the proper function of neuronal networks. The maintenance of myelin and the well-organized subtle process of myelin plasticity requires cooperation among myelin-forming cells, glial cells, and neural networks. The process of cooperation is fragile, and the balance is highly susceptible to disruption by microenvironment influences. Reactive microglia play a critical and complicated role in the demyelination and remyelination process. Recent studies have shown that the voltage-gated proton channel Hv1 is selectively expressed in microglia in CNS, which regulates intracellular pH and is involved in the production of reactive oxygen species, underlying multifaceted roles in maintaining microglia function. This paper begins by examining the molecular mechanisms of demyelination and emphasizes the crucial role of the microenvironment in demyelination. It focuses specifically on the role of Hv1 in myelin repair and its therapeutic potential in CNS demyelinating diseases. [ABSTRACT FROM AUTHOR]

Hyperhomocysteinemia (HHcy) is independently associated with poorer long-term prognosis in patients with intracerebral haemorrhage (ICH); however, the effect and mechanisms of HHcy on ICH are still unclear. Here, we evaluated neurite outgrowth and neurological functional recovery using simulated models of ICH with HHcy in vitro and in vivo. We found that the neurite outgrowth velocity and motor functional recovery in the ICH plus HHcy group were significantly slower than that in the control group, indicating that homocysteine (Hcy) significantly impedes the neurite outgrowth recovery after ICH. Furthermore, phosphoproteomic data and signalome analysis of perihematomal brain tissues suggested that calmodulin-dependent protein kinases 2 (CAMK2A) kinase substrate pairs were significantly downregulated in ICH with HHcy compared with autologous blood injection only, both western blot and immunofluorescence staining confirmed this finding. Additionally, upregulation of pCAMK2A significantly increased neurite outgrowth recovery in ICH with HHcy. Collectively, we clarify the mechanism of HHcy-hindered neurite outgrowth recovery, and pCAMK2A may serve as a therapeutic strategy for promoting neurological recovery after ICH.

Objectives: To systematically review the efficacy and safety of anti-inflammatory agents for patients with major depressive disorders.Methods: We searched the literature to identify potentially relevant randomised controlled trials (RCTs) up to 1 January 2019. The primary outcome was efficacy, measured by mean changes in depression score from baseline to endpoint. Secondary outcomes included response and remission rates and quality of life (QoL). Safety was evaluated by incidence of classified adverse events. Heterogeneity was examined using the I2 and Q statistic. Pooled standard mean differences (SMDs) and risk ratios (RRs) were calculated. Subgroup meta-analyses were conducted based on type of treatment, type of anti-inflammatory agents, sex, sponsor type and quality of studies.Results: Thirty RCTs with 1610 participants were included in the quantitative analysis. The overall analysis pooling from 26 of the RCTs suggested that anti-inflammatory agents reduced depressive symptoms (SMD -0.55, 95% CI -0.75 to -0.35, I2=71%) compared with placebo. Higher response (RR 1.52, 95% CI 1.30 to 1.79, I2=29%) and remission rates (RR 1.79, 95% CI 1.29 to 2.49, I2=41%) were seen in the group receiving anti-inflammatory agents than in those receiving placebo. Subgroup analysis showed a greater reduction in symptom severity in both the monotherapy and adjunctive treatment groups. Subgroup analysis of non-steroidal anti-inflammatory drugs, omega-3 fatty acids, statins and minocyclines, respectively, disclosed significant antidepressant effects for major depressive disorder (MDD). For women-only trials, no difference in changes of depression severity was found between groups. Subanalysis stratified by sponsor type and study quality led to the same outcomes in favour of anti-inflammatory agents in both subgroups. Changes of QoL showed no difference between the groups. Gastrointestinal events were the only significant differences between groups in the treatment periods.Conclusions: Results of this systematic review suggest that anti-inflammatory agents play an antidepressant role in patients with MDD and are reasonably safe. [ABSTRACT FROM AUTHOR]