Bright light therapy-induced improvements of mood, cognitive functions and cerebellar functional connectivity in subthreshold depression: A randomized controlled trial.

Background: The efficacy of bright light therapy (BLT) in ameliorating depression has been validated. The present study is to investigate the changes of depressive symptoms, cognitive function and cerebellar functional connectivity (FC) following BLT in individuals with subthreshold depression (StD). Method: Participants were randomly assigned to BLT group (N = 47) or placebo (N = 41) in this randomized controlled trial between March 2020 and June 2022. Depression severity and cognitive function were assessed, as well as resting-state functional MRI scan was conducted before and after 8-weeks treatment. Seed-based whole-brain static FC (sFC) and dynamic FC (dFC) analyses of the bilateral cerebellar subfields were conducted. Besides, a multivariate regression model examined whether baseline brain FC was associated with changes of depression severity and cognitive function during BLT treatment. Results: After 8-week BLT treatment, individuals with StD showed improved depressive symptoms and attention/vigilance cognitive function. BLT also increased sFC between the right cerebellar lobule IX and left temporal pole, and decreased sFC within the cerebellum, and dFC between the right cerebellar lobule IX and left medial prefrontal cortex. Moreover, the fusion of sFC and dFC at baseline could predict the improvement of attention/vigilance in response to BLT. Conclusions: The current study identified that BLT improved depressive symptoms and attention/vigilance, as well as changed cerebellum-DMN connectivity, especially in the cerebellar-frontotemporal and cerebellar internal FC. In addition, the fusion features of sFC and dFC at pre-treatment could serve as an imaging biomarker for the improvement of attention/vigilance cognitive function after BLT in StD.

Spontaneous Brain Activity Abnormalities in Patients With Temporal Lobe Epilepsy: A Meta-Analysis of 1474 Patients.

BACKGROUND: Abnormalities in resting-state functional brain activity have been detected in patients with temporal lobe epilepsy (TLE). The results of individual neuroimaging studies of TLE, however, are frequently inconsistent due to small and heterogeneous samples, analytical flexibility, and publication bias toward positive findings. PURPOSE: To investigate the most consistent regions of resting-state functional brain activity abnormality in patients with TLE through a quantitative meta-analysis of published neuroimaging data. STUDY TYPE: Meta-analysis. SUBJECTS: Exactly 1474 TLE patients (716 males and 758 females) from 31 studies on resting-state functional brain activity were included in this study. FIELD STRENGTH/SEQUENCE: Studies utilizing 1.5 T or 3 T MR scanners were included for meta-analysis. Resting-state functional MRI using gradient echo-planar imaging, T1-weighted imaging. ASSESSMENT: PubMed, Web of Science, Chinese National Knowledge Infrastructure, and WanFang databases were searched to identify studies investigating amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo) at the whole-brain level between patients with TLE and healthy controls (HCs). STATISTICAL TESTS: Seed-based d Mapping with Permutation of Subject Images, standard randomization tests and meta-regression analysis were used. Results were significant if P < 0.05 with family-wise error corrected. RESULTS: Patients with TLE displayed resting-state functional brain activity which was a significant increase in the right hippocampus, and significant decrease in the right angular gurus and right precuneus. Additionally, the meta-regression analysis demonstrated that age (P = 0.231), sex distribution (P = 0.376), and illness duration (P = 0.184), did not show significant associations with resting state functional brain activity in patients with TLE. DATA CONCLUSION: Common alteration patterns of spontaneous brain activity were identified in the right hippocampus and default-model network regions in patients with TLE. These findings may contribute to understanding of the underlying mechanism for potentially effective intervention of TLE. TECHNICAL EFFICACY STAGE: Stage 2.

COVID-19 is associated with changes in brain function and structure: A multimodal meta-analysis of neuroimaging studies.

The actual role of coronavirus disease 2019 (COVID-19) in brain damage has been increasingly reported, necessitating a meta-analysis to collate and summarize the inconsistent findings from functional imaging and voxel-based morphometry (VBM) studies. A comprehensive voxel-wise meta-analysis of the whole brain was conducted to identify alterations in functional activity and gray matter volume (GMV) between COVID-19 patients and healthy controls (HCs) by using Seed-based d Mapping software. We included 15 functional imaging studies (484 patients with COVID-19, 534 HCs) and 9 VBM studies (449 patients with COVID-19, 388 HCs) in the analysis. Overall, patients with COVID-19 exhibited decreased functional activity in the right superior temporal gyrus (STG) (extending to the right middle and inferior temporal gyrus, insula, and temporal pole [TP]), left insula, right orbitofrontal cortex (OFC) (extending to the right olfactory cortex), and left cerebellum compared to HCs. For VBM, patients with COVID-19, relative to HCs, showed decreased GMV in the bilateral anterior cingulate cortex/medial prefrontal cortex (extending to the bilateral OFC), and left cerebellum, and increased GMV in the bilateral amygdala (extending to the bilateral hippocampus, STG, TP, MTG, and right striatum). Moreover, overlapping analysis revealed that patients with COVID-19 exhibited both decreased functional activity and increased GMV in the right TP (extending to the right STG). The multimodal meta-analysis suggests that brain changes of function and structure in the temporal lobe, OFC and cerebellum, and functional or structural alterations in the insula and the limbic system in COVID-19. These findings contribute to a better understanding of the pathophysiology of brain alterations in COVID-19. SIGNIFICANCE STATEMENT: This first large-scale multimodal meta-analysis collates existing neuroimaging studies and provides voxel-wise functional and structural whole-brain abnormalities in COVID-19. Findings of this meta-analysis provide valuable insights into the dynamic brain changes (from infection to recovery) and offer further explanations for the pathophysiological basis of brain alterations in COVID-19.

Gut proinflammatory bacteria is associated with abnormal functional connectivity of hippocampus in unmedicated patients with major depressive disorder.

Accumulating evidence has revealed the gut bacteria dysbiosis and brain hippocampal functional and structural alterations in major depressive disorder (MDD). However, the potential relationship between the gut microbiota and hippocampal function alterations in patients with MDD is still very limited. Data of resting-state functional magnetic resonance imaging were acquired from 44 unmedicated MDD patients and 42 demographically matched healthy controls (HCs). Severn pairs of hippocampus subregions (the bilateral cornu ammonis [CA1-CA3], dentate gyrus (DG), entorhinal cortex, hippocampal-amygdaloid transition area, and subiculum) were selected as the seeds in the functional connectivity (FC) analysis. Additionally, fecal samples of participants were collected and 16S rDNA amplicon sequencing was used to identify the altered relative abundance of gut microbiota. Then, association analysis was conducted to investigate the potential relationships between the abnormal hippocampal subregions FC and microbiome features. Also, the altered hippocampal subregion FC values and gut microbiota levels were used as features separately or together in the support vector machine models distinguishing the MDD patients and HCs. Compared with HCs, patients with MDD exhibited increased FC between the left hippocampus (CA2, CA3 and DG) and right hippocampus (CA2 and CA3), and decreased FC between the right hippocampal CA3 and bilateral posterior cingulate cortex. In addition, we found that the level of proinflammatory bacteria (i.e., Enterobacteriaceae) was significantly increased, whereas the level of short-chain fatty acids producing-bacteria (i.e., Prevotellaceae, Agathobacter and Clostridium) were significantly decreased in MDD patients. Furthermore, FC values of the left hippocampal CA3- right hippocampus (CA2 and CA3) was positively correlated with the relative abundance of Enterobacteriaceae in patients with MDD. Moreover, altered hippocampal FC patterns and gut microbiota level were considered in combination, the best discrimination was obtained (AUC = 0.92). These findings may provide insights into the potential role of gut microbiota in the underlying neuropathology of MDD patients.

A case of scrub typhus with meningitis as the onset: Case report and literature review.

RATIONALE: Scrub typhus is a naturally occurring acute febrile disease caused by Orientia tsutsugamushi. Although it can cause multiple organ dysfunction, central nervous system infections are uncommon. PATIENT CONCERNS: A 17-year-old male presented with a 5-day history of fever and headaches. The MRI of the head revealed thickness and enhancement of the left temporal lobe and tentorium cerebelli, indicating potential inflammation. DIAGNOSES: The patient was diagnosed with a central nervous system infection. INTERVENTIONS: Ceftriaxone and acyclovir were administered intravenously to treat the infection, reduce fever, restore acid-base balance, and manage electrolyte disorders. OUTCOMES: Despite receiving ceftriaxone and acyclovir as infection therapy, there was no improvement. Additional multipathogen metagenomic testing indicated the presence of O tsutsugamushi infection, and an eschar was identified in the left axilla. The diagnosis was changed to scrub typhus with meningitis and the therapy was modified to intravenous doxycycline. Following a 2-day therapy, the body temperature normalized, and the fever subsided. CONCLUSIONS: The patient was diagnosed with scrub typhus accompanied by meningitis, and doxycycline treatment was effective. LESSION: Rarely reported cases of scrub typhus with meningitis and the lack of identifiable symptoms increase the chance of misdiagnosis or oversight. Patients with central nervous system infections presenting with fever and headache unresponsive to conventional antibacterial and antiviral treatment should be considered for scrub typhus with meningitis. Prompt multipathogen metagenomic testing is recommended to confirm the diagnosis and modify the treatment accordingly.

Systematic review and meta-analysis: multimodal functional and anatomical neural alterations in autism spectrum disorder.

BACKGROUND: This meta-analysis aimed to explore the most robust findings across numerous existing resting-state functional imaging and voxel-based morphometry (VBM) studies on the functional and structural brain alterations in individuals with autism spectrum disorder (ASD). METHODS: A whole-brain voxel-wise meta-analysis was conducted to compare the differences in the intrinsic functional activity and gray matter volume (GMV) between individuals with ASD and typically developing individuals (TDs) using Seed-based d Mapping software. RESULTS: A total of 23 functional imaging studies (786 ASD, 710 TDs) and 52 VBM studies (1728 ASD, 1747 TDs) were included. Compared with TDs, individuals with ASD displayed resting-state functional decreases in the left insula (extending to left superior temporal gyrus [STG]), bilateral anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), left angular gyrus and right inferior temporal gyrus, as well as increases in the right supplementary motor area and precuneus. For VBM meta-analysis, individuals with ASD displayed decreased GMV in the ACC/mPFC and left cerebellum, and increased GMV in the left middle temporal gyrus (extending to the left insula and STG), bilateral olfactory cortex, and right precentral gyrus. Further, individuals with ASD displayed decreased resting-state functional activity and increased GMV in the left insula after overlapping the functional and structural differences. CONCLUSIONS: The present multimodal meta-analysis demonstrated that ASD exhibited similar alterations in both function and structure of the insula and ACC/mPFC, and functional or structural alterations in the default mode network (DMN), primary motor and sensory regions. These findings contribute to further understanding of the pathophysiology of ASD.

Case report of recurrent epistaxis caused by a live leech in the nasal cavity.

RATIONALE: Epistaxis is one of the common emergencies in otolaryngology. There are many causes of epistaxis, but reports of epistaxis due to nasal foreign bodies like leeches are rare. PATIENT CONCERNS: A 55-year-old male presented with "repeated epistaxis for over 20 days." Nasal endoscopy revealed a live leech in the olfactory area of the left nostril. DIAGNOSES: The patient was diagnosed with epistaxis caused by a live leech in the nasal cavity. INTERVENTIONS: Under nasal endoscopy, the leech was grasped with a vascular clamp and removed from the nasal cavity. The leech measured 8 cm in length. Hemostasis was achieved using a gelatin sponge at the wound site, and the nasal cavity was packed with Vaseline gauze. OUTCOMES: The live leech was removed via nasal endoscopy. Two days later, the Vaseline gauze packing was removed, and the patient experienced no further nasal bleeding. CONCLUSION: Live leeches in the nasal cavity can cause epistaxis. Nasal endoscopic removal of the live leech is an effective treatment. LESSON: There are many causes of epistaxis, which are nonspecific and prone to missed or incorrect diagnosis. In patients with a history of fieldwork or direct contact with leeches who present with recurrent nasal bleeding, the possibility of epistaxis caused by a live leech should be considered, and timely and effective treatment should be provided.

A literature review and meta-analysis of the optimal factors study of repetitive transcranial magnetic stimulation in post-infarction aphasia.

BACKGROUND: The existing literature indicates that repetitive transcranial magnetic stimulation (rTMS) can potentially enhance the prognosis of poststroke aphasia (PSA). Nevertheless, these investigations did not identify the most effective parameters or settings for achieving optimal treatment outcomes. This study involved a meta-analysis aimed to identify the optimal variables for rTMS in treating post-infarction aphasia to guide the use of rTMS in rehabilitating PSA. METHODS: PubMed, Embase, and Cochrane Library databases were searched from inception to May 2023, and articles were reviewed manually using subject words and free words and supplemented with references from the included literature to obtain additional relevant literature. The search terms included "poststroke aphasia" and "repetitive transcranial magnetic stimulation (rTMS)" repetitive transcranial magnetic stimulation. Additionally, a review of the reference lists of previously published systematic reviews identified through the Cochrane Database of Systematic Reviews (search terms: poststroke aphasia, rTMS; restrictions: none) and PubMed (search terms: poststroke aphasia, rTMSs; restrictions: systematic review or meta-analysis) was performed. Information from studies involving different doses of rTMS in PSA was independently screened and extracted by 2 researchers. RESULTS: This meta-analysis included 387 participants with PSA across 18 randomized controlled trials. The results showed that the total pulse had a trend toward a significant correlation with the treatment effect (P = 0.088), while all other variables did not correlate significantly. When rTMS was not grouped by stimulus parameter and location, our nonlinear results showed that when the total pulses were 40,000 (standardized mean difference (SMD):1.86, 95% credible interval (CrI) 0.50 to 3.33), the pulse/session was 1000 (SMD:1.05, 95% CrI 0.55-1.57), and an RMT of 80% (SMD:1.08, 95% CrI 0.60-1.57) had the best treatment effect. When rTMS was grouped by stimulus parameters and location, our nonlinear results showed that when the total low-frequency (LF)-rTMS-right inferior frontal gyrus (RIFG) pulse was 40,000 (SMD:1.76, 95% CrI:0.36-3.29), the pulse/session was 1000 (SMD:1.06, 95% CrI:0.54-1.59). Optimal results were obtained with an RMT of 80% (SMD:1.14, 95% CrI 0.54 - 1.76). CONCLUSIONS: The optimal treatment effects of rTMS for PSA may be obtained with a total pulse of 40,000, a pulse/session of 1000, and an RMT of 80%. Further rigorous randomized controlled studies are required to substantiate the validity of these results.

Increased functional connectivity between the midbrain and frontal cortex following bright light therapy in subthreshold depression: A randomized clinical trial.

The underlying mechanisms of bright light therapy (BLT) in the prevention of individuals with subthreshold depression symptoms are yet to be elucidated. The goal of the study was to assess the correlation between midbrain monoamine-producing nuclei treatment-related functional connectivity (FC) changes and depressive symptom improvements in subthreshold depression. This double-blind, randomized, placebo-controlled clinical trial was conducted between March 2020 and June 2022. A total of 74 young adults with subthreshold depression were randomly assigned to receive 8-week BLT (N = 38) or placebo (N = 36). Depression severity was measured using the Hamilton Depression Rating Scale (HDRS). The participants underwent resting-state functional magnetic resonance imaging at baseline and after treatment. The dorsal raphe nucleus (DRN), ventral tegmental area (VTA), and habenula seed-based whole-brain FC were analyzed. A multivariate regression model examined whether baseline brain FC was associated with changes in scores on HDRS during BLT treatment. BLT group displayed significantly decreased HDRS scores from pre- to posttreatment compared to the placebo group. BLT increased the FC between the DRN and medial prefrontal cortex (mPFC) and between the left VTA and right superior frontal gyrus (SFG). Altered VTA-SFG connectivity was associated with HDRS changes in the BLT group. Moreover, the baseline FC between DRN and mPFC could predict HDRS changes in BLT. These results suggested that BLT improves depressive symptoms and increases midbrain monoamine-producing nuclei and frontal cortex connectivity in subthreshold depression, which raises the possibility that pretreatment FC of DRN-mPFC could be used as a biomarker for improved BLT treatment in depression. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A multimodal meta-analysis of regional functional and structural brain abnormalities in obsessive-compulsive disorder.

Numerous neuroimaging studies of resting-state functional imaging and voxel-based morphometry (VBM) have revealed abnormalities in specific brain regions in obsessive-compulsive disorder (OCD), but results have been inconsistent. We conducted a whole-brain voxel-wise meta-analysis on resting-state functional imaging and VBM studies that investigated differences of functional activity and gray matter volume (GMV) between patients with OCD and healthy controls (HCs) using seed-based d mapping (SDM) software. A total of 41 independent studies (51 datasets) for resting-state functional imaging and 42 studies (46 datasets) for VBM were included by a systematic literature search. Overall, patients with OCD displayed increased spontaneous functional activity in the bilateral inferior frontal gyrus (IFG) (extending to the bilateral insula) and bilateral medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC), as well as decreased spontaneous functional activity in the bilateral paracentral lobule, bilateral cerebellum, left caudate nucleus, left inferior parietal gyri, and right precuneus cortex. For the VBM meta-analysis, patients with OCD displayed increased GMV in the bilateral thalamus (extending to the bilateral cerebellum), right striatum, and decreased GMV in the bilateral mPFC/ACC and left IFG (extending to the left insula). The conjunction analyses found that the bilateral mPFC/ACC, left IFG (extending to the left insula) showed decreased GMV with increased intrinsic function in OCD patients compared to HCs. This meta-analysis demonstrated that OCD exhibits abnormalities in both function and structure in the bilateral mPFC/ACC, insula, and IFG. A few regions exhibited only functional or only structural abnormalities in OCD, such as the default mode network, striatum, sensorimotor areas, and cerebellum. It may provide useful insights for understanding the underlying pathophysiology of OCD and developing more targeted and efficacious treatment and intervention strategies.

Functional and structural brain abnormalities in substance use disorder: A multimodal meta-analysis of neuroimaging studies.

INTRODUCTION: Numerous neuroimaging studies of resting-state functional imaging and voxel-based morphometry (VBM) have revealed that patients with substance use disorder (SUD) may present brain abnormalities, but their results were inconsistent. This multimodal neuroimaging meta-analysis aimed to estimate common and specific alterations in SUD patients by combining information from all available studies of spontaneous functional activity and gray matter volume (GMV). METHODS: A whole-brain meta-analysis on resting-state functional imaging and VBM studies was conducted using the Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) software, followed by multimodal overlapping to comprehensively investigate function and structure of the brain in SUD. RESULTS: In this meta-analysis, 39 independent studies with 47 datasets related to resting-state functional brain activity (1444 SUD patients; 1446 healthy controls [HCs]) were included, as well as 77 studies with 89 datasets for GMV (3457 SUD patients; 3774 HCs). Patients with SUD showed the decreased resting-state functional brain activity in the bilateral anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC). For the VBM meta-analysis, patients with SUD showed the reduced GMV in the bilateral ACC/mPFC, insula, thalamus extending to striatum, and left sensorimotor cortex. CONCLUSIONS: This multimodal meta-analysis exhibited that SUD shows common impairment in both function and structure in the ACC/mPFC, suggesting that the deficits in functional and structural domains could be correlated together. In addition, a few regions exhibited only structural impairment in SUD, including the insula, thalamus, striatum, and sensorimotor areas.

An Intelligent Tongue Diagnosis System via Deep Learning on the Android Platform.

To quickly and accurately identify the pathological features of the tongue, we developed an intelligent tongue diagnosis system that uses deep learning on a mobile terminal. We also propose an efficient and accurate tongue image processing algorithm framework to infer the category of the tongue. First, a software system integrating registration, login, account management, tongue image recognition, and doctor-patient dialogue was developed based on the Android platform. Then, the deep learning models, based on the official benchmark models, were trained by using the tongue image datasets. The tongue diagnosis algorithm framework includes the YOLOv5s6, U-Net, and MobileNetV3 networks, which are employed for tongue recognition, tongue region segmentation, and tongue feature classification (tooth marks, spots, and fissures), respectively. The experimental results demonstrate that the performance of the tongue diagnosis model was satisfying, and the accuracy of the final classification of tooth marks, spots, and fissures was 93.33%, 89.60%, and 97.67%, respectively. The construction of this system has a certain reference value for the objectification and intelligence of tongue diagnosis.

Functional and structural brain abnormalities in posttraumatic stress disorder: A multimodal meta-analysis of neuroimaging studies.

BACKGROUND: Numerous resting-state functional and structural studies have revealed that many brain regions are involved in the pathogenesis of posttraumatic stress disorder (PTSD), but their findings have been inconsistent. Moreover, there has no study explored the functional and structural alterations across languages in PTSD. METHODS: A meta-analysis of whole-brain on the amplitude of low-frequency fluctuation (ALFF) and voxel-based morphometry (VBM) studies that explored alterations in the spontaneous functional brain activity and grey matter volume (GMV) in PTSD patients across languages by using the Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) software. RESULTS: A total of 15 studies (19 datasets) comprising 577 PTSD patients and 499 HCs for ALFF, and 27 studies (31 datasets) comprising 539 PTSD patients and 693 HCs for VBM were included. Overall, PTSD patients across languages displayed decreased ALFF in the in the left amygdala. For VBM meta-analysis, PTSD patients across languages displayed reduced GMV in the bilateral anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), striatum, insula, superior temporal gyrus, left postcentral gyrus, and occipital gyrus. CONCLUSIONS: The multimodal meta-analysis suggest that PTSD patients showed similar pattern of aberrant resting-state functional brain activity and structure mainly in the amygdala, suggesting that structural deficits might underlie alterations in function. In addition, some regions exhibited only structural abnormalities in PTSD, including the ACC/mPFC, striatum, insula, primary visual, auditory and sensorimotor cortices. Moreover, consistent alterations in PTSD patients across languages may draw attention to the disparity in multi-cultural considerations in psychiatric research and further understanding the neurophysiopathology of PTSD.

A Novel Long-circulating DOX Liposome: Formulation and Pharmacokinetics Studies.

BACKGROUND: Doxorubicin (DOX) is a leading chemotherapeutic in cancer treatment because of its high potency and broad spectrum. Liposomal doxorubicin (Doxil®) is the first FDA-approved PEG-liposomes of DOX for the treatment of over 600,000 cancer patients, and it can overcome doxorubicin-induced cardiomyopathy and other side effects and prolong life span. The addition of MPEG2000-DSPE could elevate the total cost of cancer treatment. OBJECTIVE: We intended to prepare a novel DOX liposome that was prepared with inexpensive materials egg yolk lecithin and Kolliphor HS15, thus allowing it to be much cheaper for clinical application. METHODS: DOX liposomes were prepared using the combination of thin-film dispersion ultrasonic method and ammonium sulfate gradient method and the factors that influenced formulation quality were optimized. After formulation, particle size, entrapment efficiency, drug loading, stability, and pharmacokinetics were determined. RESULTS: DOX liposomes were near-spherical morphology with the average size of 90 nm and polydispersity index (PDI) of less than 0.30. The drug loading was up to 7.5%, and the entrapment efficiency was over 80%. The pharmacokinetic studies showed that free DOX could be easily removed and the blood concentration of free DOX group was significantly lower than that of DOX liposomes, which indicated that the novel DOX liposome had a certain sustainedrelease effect. CONCLUSION: In summary, DOX liposome is economical and easy-prepared with prolonged circulation time. Lay Summary: Doxorubicin (DOX) is a leading chemotherapeutic in cancer treatment because of its high potency and broad spectrum. Liposomal doxorubicin (Doxil®) is the first FDAapproved PEG-liposomes of DOX to treat over 600.000 cancer patients, overcoming doxorubicin- induced cardiomyopathy and other side effects and prolonging life span. The addition of MPEG2000-DSPE could elevate the total cost of cancer treatment. We intend to prepare a novel DOX liposome prepared with inexpensive materials egg yolk lecithin and Kolliphor HS15, thus allowing it to be much cheaper for clinical use. The novel DOX liposome is economical and easy-prepared with prolonged circulation time.

Identification of crucial genes associated with rat traumatic spinal cord injury.

The aim of the present study was to investigate the key genes associated with traumatic spinal cord injuries (TSCI). The dataset GSE52763 was downloaded from the Gene Expression Omnibus, for which lumbar spinal cord samples were obtained from rats at 1 and 3 weeks following contusive spinal cord injury and 1 week subsequent to a sham laminectomy, and used to identify differentially expressed genes (DEGs). Functional enrichment analysis, co­expression analysis and transcription factor (TF) identification were performed for DEGs common to the 1 and 3 week injury samples. In total, 234 upregulated and 51 downregulated DEGs were common to the 1 and 3 week injury samples. The upregulated DEGs were significantly enriched in Gene Ontology terms concerning immunity (e.g. Itgal and Ccl2) and certain pathways, including natural killer cell mediated cytotoxicity [e.g. Ras­related C3 botulinum toxin substrate 2 (Rac2) and TYRO protein tyrosine kinase binding protein (Tyrobp)]. The downregulated DEGs were highly enriched in female gonad development [e.g. progesterone receptor (Pgr)], and the steroid biosynthesis pathway. A total of 139 genes had co­expression associations and the majority of them were upregulated genes. The upregulated co­expressed genes were predominantly enriched in biological regulation, including TGFB induced factor homeobox 1 (Tgif1) and Rac2. The downregulated co­expressed genes were enriched in anatomical structure development (e.g. Dnm3). A total of 92 co­expressed genes composed the protein­protein interaction network. Additionally, 9 TFs (e.g. Pgr and Tgif1) were identified from the DEGs. It was hypothesized that the genes including Tgif1, Rac2, Tyrobp, and Pgr may be closely associated with TSCI.

Efficacy evaluation of methotrexate in the treatment of ankylosing spondylitis using meta-analysis.

The aim of this study was to evaluate the efficacy of methotrexate (MTX) in the treatment of ankylosing spondylitis (AS). The literature on controlled clinical trials was searched from MEDLINE, EMBASE, OVID, and Cochrane Library databases up to November 2012. The quality of the studies included was evaluated publicly by two reviewers. A meta-analysis was conducted to the homogeneous studies using Cochrane systematic review. Three trials involving 116 patients compared treatment with MTX against placebo. No statistically significant differences (p < 0.05) were found in the primary outcome measures of withdrawal rate, bath ankylosing spondilitis active index (BASDAI), C-reactive protein (CRP), patient global assessment, and side effects such as nausea and vomiting. Two trials involving 142 patients compared treatment with MTX plus infliximab (IFX) against IFX alone in the effect of treatment of AS. No statistically significant differences (p < 0.05) were found in the primary outcome measures of ASAS20 and withdrawal rate. Thus, we should choose the right drugs based on the specific situation in clinical applications. Randomized controlled trials designed rationally and implemented strictly with multi-center, large sample size and enough follow-up time are needed in future research.