Voxel-wise meta-analyses of brain blood flow and local synchrony abnormalities in medication-free patients with major depressive disorder.

BACKGROUND: Published meta-analyses of resting-state regional cerebral blood flow (rCBF) studies of major depressive disorder (MDD) have included patients receiving antidepressants, which might affect brain activity and thus bias the results. To our knowledge, no meta-analysis has investigated regional homogeneity changes in medication-free patients with MDD. Moreover, an association between regional homogeneity and rCBF has been demonstrated in some brain regions in healthy controls. We sought to explore to what extent resting-state rCBF and regional homogeneity changes co-occur in the depressed brain without the potential confound of medication. METHODS: Using the effect-size signed differential mapping method, we conducted 2 meta-analyses of rCBF and regional homogeneity studies of medication-free patients with MDD. RESULTS: Our systematic search identified 14 rCBF studies and 9 regional homogeneity studies. We identified conjoint decreases in resting-state rCBF and regional homogeneity in the insula and superior temporal gyrus in medication-free patients with MDD compared with controls. Other changes included altered resting-state rCBF in the precuneus and in the frontal-limbic-thalamic-striatal neural circuit as well as altered regional homogeneity in the uncus and parahippocampal gyrus. Meta-regression revealed that the percentage of female patients with MDD was negatively associated with resting-state rCBF in the right anterior cingulate cortex and that the age of patients with MDD was negatively associated with rCBF in the left insula and with regional homogeneity in the left uncus. LIMITATIONS: The analysis techniques, patient characteristics and clinical variables of the included studies were heterogeneous. CONCLUSION: The conjoint alterations of rCBF and regional homogeneity in the insula and superior temporal gyrus may be core neuropathological changes in medication-free patients with MDD and serve as a specific region of interest for further studies on MDD.

Activation of free fatty acid receptors, FFAR1 and FFAR4, ameliorates ulcerative colitis by promote fatty acid metabolism and mediate macrophage polarization.

OBJECTIVE: To investigate the mechanism of action of fatty acid receptors, FFAR1 and FFAR4, on ulcerative colitis (UC) through fatty acid metabolism and macrophage polarization. METHODS: Dextran sulfate sodium (DSS)-induced mouse model of UC mice was used to evaluate the efficacy of FFAR1 (GW9508) and FFAR4 (GSK137647) agonists by analyzing body weight, colon length, disease activity index (DAI), and histological scores. Real-time PCR and immunofluorescence analysis were performed to quantify the levels of fatty acid metabolizing enzymes and macrophage makers. FFA-induced lipid accumulation in RAW264.7 cells was visualized by Oil Red O staining analysis, and cells were collected to detect macrophage polarization by flow cytometry. RESULTS: The combination of GW9508 and GSK137647 significantly improved DSS-induced UC symptoms, caused recovery in colon length, and decreased histological injury. GW9508 + GSK137647 treatment upregulated the expressions of CD206, lipid oxidation enzyme (CPT-1α) and anti-inflammatory cytokines (IL-4, IL-10, IL-13) but downregulated those of CD86, lipogenic enzymes (ACC1, FASN, SCD1), and pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α). Combining the two agonists decreased FFA-induced lipid accumulation and increased CD206 expression in cell-based experiments. CONCLUSION: Activated FFAR1 and FFAR4 ameliorates DSS-induced UC by promoting fatty acid metabolism to reduce lipid accumulation and mediate M2 macrophage polarization.

Impact of acute stress on human brain microstructure: An MR diffusion study of earthquake survivors.

A characterization of the impact of natural disasters on the brain of survivors is critical for a better understanding of posttraumatic responses and may inform the development of more effective early interventions. Here we report alterations in white matter microstructure in survivors soon after Wenchuan earthquake in China in 2008. Within 25 days after the Wenchuan earthquake, 44 healthy survivors were recruited and scanned on a 3T MR imaging system. The survivors were divided into two groups according to their self-rating anxiety scale (SAS) score, including the SAS(+) (SAS > 55 after correction) group and "SAS(-)" (SAS < 55 after correction) group. Thrity-two healthy volunteers were also recruited as control group before earthquake. Individual maps of fractional anisotropy (FA) were calculated and voxel-based analysis (VBA) was performed to allow the comparison between survivors and controls using ANCOVAs in SPM2. In addition, a correlation between SAS score and regional FA value was examined using Pearson's correlation analysis in SPSS 11.5. Compared with the healthy cohort, the whole group of 44 survivors showed significantly decreased FA values in the right prefrontal lobe, the parietal lobe, the basal ganglia, and the right parahippocampus. These effects did not appear to depend on self-rating anxiety. For the first time we provide evidence that acute trauma altered cerebral microstructure within the limbic system; furthermore, these alterations are evident shortly after the traumatic event, highlighting the need for early evaluation and intervention for trauma survivors.

Brain structural plasticity in survivors of a major earthquake.

BACKGROUND: Stress responses have been studied extensively in animal models, but effects of major life stress on the human brain remain poorly understood. The aim of this study was to determine whether survivors of a major earthquake, who were presumed to have experienced extreme emotional stress during the disaster, demonstrate differences in brain anatomy relative to individuals who have not experienced such stressors. METHODS: Healthy survivors living in an area devastated by a major earthquake and matched healthy controls underwent 3-dimentional high-resolution magnetic resonance imaging (MRI). Survivors were scanned 13-25 days after the earthquake; controls had undergone MRI for other studies not long before the earthquake. We used optimized voxel-based morphometry analysis to identify regional differences of grey matter volume between the survivors and controls. RESULTS: We included 44 survivors (17 female, mean age 37 [standard deviation (SD) 10.6] yr) and 38 controls (14 female, mean age 35.3 [SD 11.2] yr) in our analysis. Compared with controls, the survivors showed significantly lower grey matter volume in the bilateral insula, hippocampus, left caudate and putamen, and greater grey matter volume in the bilateral orbitofrontal cortex and the parietal lobe (all p < 0.05, corrected for multiple comparison). LIMITATIONS: Differences in the variance of survivor and control data could impact study findings. CONCLUSION: Acute anatomic alterations could be observed in earthquake survivors in brain regions where functional alterations after stress have been described. Anatomic changes in the present study were observed earlier than previously reported and were seen in prefrontal-limbic, parietal and striatal brain systems. Together with the results of previous functional imaging studies, our observations suggest a complex pattern of human brain response to major life stress affecting brain systems that modulate and respond to heightened affective arousal.

Effects of slanted bilateral lateral recession vs conventional bilateral lateral recession on convergence insufficiency intermittent exotropia: a prospective study.

AIM: To observe the surgical effects of slanted bilateral lateral recession (S-BLR) versus conventional bilateral lateral recession (C-BLR) in convergence insufficiency intermittent exotropia (CI-IXT). METHODS: Using a randomized, double-blind, prospective design, 22 patients with CI-IXT who were admitted to Renmin Hospital of Wuhan University from July 2019 to December 2020 were included. Patients were randomly divided into either S-BLR or C-BLR group for their subsequent strabismus surgery. All patients were followed up for 12mo. Near deviation, distant deviation, and near-distance difference (NDD) were measured in all patients. RESULTS: Twelve months after surgery, NDD improvement was 10 (8, 13) prismatic degrees (PD) in S-BLR group and 3 (1, 6) PD in C-BLR group (P=0.011). The near deviation of S-BLR group was 0 (-2, 2) PD, while that of C-BLR group was -4 (-6, -3) PD (P=0.005). Before and after surgery, the difference in the distant deviation between the two groups was not statistically significant. There was no statistically significant difference in near stereopsis between the two groups (P=0.380) at 12mo. The success rate at 12mo after operation was 90.91% and 72.73% in the two groups (P=0.280). CONCLUSION: CI-IXT patients treated with S-BLR have better surgical outcomes than those treated with C-BLR, which indicates S-BLR is a safe and effective operation pattern.

[Epidemiological survey on neuropsychiatric disorders in Tibet of China: neuroses, alcohol-related disorders, mental retardation and epilepsy].

OBJECTIVE: To investigate the prevalence of four common neuropsychiatric disorders in Tibet, with an aim to providing information support to health planning. METHODS: The survey was carried out in four regions of Tibet. The sampling strategy was adapted from that of a national psychiatric epidemiological survey in China in 1982 and 1993. The Neurosis Screening Inventory, Screening Inventory for Alcohol Dependence and Related Problems, Child Intelligence Screening Inventory, and a questionnaire for the Detection of Epileptic Seizures were administered to the respondents through face to face interview. Those with a positive response and 10% of those with a negative response were further interviewed with the Structured Clinical Interview for DSM-IV Axis I Disorders (research version) (SCID-I ). Anxiety disorders and alcohol used disorders were diagnosed according to the American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders (4th edition) (DSM-IV). Hysteria and mental retardation were diagnosed according to the International Classification of Diseases, 10th edition (ICD-10), and the Chinese Classification of Mental Disorders, 3rd edition (CCMD-3). RESULTS: The point prevalence of neuroses, alcohol-related disorders, mental retardation and epilepsy was 2. 56%, 4. 06%, 0. 28% and 0. 68%, respectively. The lifetime prevalence of neuroses, alcohol-related disorders, mental retardation and epilepsy was 2. 62%, 4. 24%, 0. 28% and 0.72%, respectively. CONCLUSION: Alcohol-related disorders and neuroses are the two common mental health problems in Tibet. Mental retardation and epilepsy are the two serious neuropsychiatric disorders affecting Tibetan children and adolescence. These disorders should be identified as priorities in the reginonal health planning in Tibet.

Efficacy and Safety of Drug-Eluting Beads Transarterial Chemoembolization Combining Immune Checkpoint Inhibitors in Unresectable Intrahepatic Cholangiocarcinoma: A Propensity Score Matching Analysis.

Purpose: To assess the effectiveness and safety of drug-eluting beads transarterial chemoembolization plus immune checkpoint inhibitors (DEB-TACE+ICIs) versus chemotherapy (gemcitabine+cisplatin) for patients with unresectable intrahepatic cholangiocarcinoma (iCCA). Materials and Methods: This retrospective study included unresectable iCCA patients treated with DEB-TACE+ICIs or chemotherapy between May, 2019 and August, 2021. The differences in tumor responses, progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs) were compared between the 2 groups. Patient baseline characteristics, PFS, and OS were compared among 2 groups before and after propensity score-matching (PSM). Factors affecting PFS and OS were analyzed by Cox's proportional hazards regression model. Results: The study included 49 patients with unresectable iCCA patients, 20 in the DEB-TACE+ICIs group and 29 in the chemotherapy group. PSM analysis created 20 pairs of patients in 2 groups. The patients in the DEB-TACE+ICIs group had a higher objective response rate (55.0% vs. 20.0%, P=0.022), higher PFS (median, 7.2 vs. 5.7 months, P=0.036), and higher OS (median, 13.2 vs. 7.6 months, P=0.015) than those in the chemotherapy group. Multivariate analyses suggested that chemotherapy, tumor size >5cm, and multiple tumors were the independent risk factors for PFS and OS. The incidence of TRAEs was similar between the 2 groups. Conclusion: Compared to chemotherapy, DEB-TACE plus ICIs improved survival and was well-tolerated in patients with unresectable iCCA.

Clinical efficacy of botulinum toxin type A on acute acquired comitant esotropia.

AIM: To investigate the effects of micro-injection of botulinum toxin A (BTXA) on acute acquired comitant esotropia (AACE). METHODS: A total of 33 AACE patients who underwent BTXA micro-injection at Renmin Hospital of Wuhan University from September 1st, 2019 to July 1st, 2021 were retrospective analyzed. Esotropia, eye alignment, stereopsis, and complications were examined at baseline (except complications), 1wk, 1, 3, and 6mo after injection. RESULTS: The average angle of deviation before injection was (+20.24±6.80)Δ at near and (+24.76±6.43)Δ at distance, while (+5.15±5.85)Δ at near and (+7.30±6.17)Δ at distance 6mo after treatment (P<0.05). Six months after injection, the stereopsis of patients had improved. The number of patients having no stereopsis (>800 seconds of arc) decreased from 11 to 3. The number of patients having peripheral stereopsis (300-800 seconds of arc), macular stereopsis (70-200 seconds of arc) and central concave stereopsis (≤60 seconds of arc) increased from 10 to 11, 10 to 12, and 2 to 7, respectively. At the follow-ups at 1wk, 1, 3, and 6mo after injection, success rates were 96.97%, 96.97%, 93.94% and 87.88%, respectively. One week after injection, two patients (6.07%) showed subconjunctival hemorrhage; three patients (9.09%) showed limited eye movement and one patient (3.03%) showed mild vertical strabismus. All the symptoms disappeared by the final follow-up. CONCLUSION: Micro-injection of BTXA can reduce diplopia and improve binocular vision function of AACE patients. Furthermore, the operation is relatively safe with few complications, making it an ideal treatment modality for AACE.

Efficacy and safety of transarterial chemoembolization combining sorafenib with or without immune checkpoint inhibitors in previously treated patients with advanced hepatocellular carcinoma: A propensity score matching analysis.

Purpose: To compare the efficacy and safety of transarterial chemoembolization (TACE) plus sorafenib and immune checkpoint inhibitors (T+S+ICIs) and TACE plus sorafenib (T+S) when treating patients with advanced hepatocellular carcinoma (HCC) who have previously received locoregional treatment. Materials and methods: A retrospective analysis was performed on the patients with Barcelona Clinic Liver Cancer (BCLC) stage C HCC from May 2019 to December 2020. These patients were treated with locoregional therapy and showed radiographic progression after the treatment. Patients received either T+S+ICIs or T+S. The outcomes, including disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety, were compared. The propensity score matching (PSM) methodology was used to reduce the influence of confounding factors on the outcomes. Results: Forty-three patients were included in the T+S group and 33 in the T+S+ICI group. After PSM (n = 29 in each group), patients who received T+S+ICIs had a higher DCR (82.8% vs. 58.6%, p = 0.043), longer median PFS (6.9 vs. 3.8 months, p = 0.003), and longer median OS (12.3 vs. 6.3 months, p = 0.008) than those who underwent T+S. Eastern Cooperative Oncology Group performance status was an independent predictor of PFS, and age was an independent predictor of OS. The incidence of treatment-related adverse events in T+S+ICIs was well controlled. Conclusions: Compared with TACE combined with sorafenib, TACE combined with sorafenib plus ICIs is a potentially safe and effective treatment regimen for patients with advanced HCC who previously received locoregional treatment.

Huangqin decoction ameliorates DSS-induced ulcerative colitis: Role of gut microbiota and amino acid metabolism, mTOR pathway and intestinal epithelial barrier.

BACKGROUND: The clinical treatment of ulcerative colitis (UC) is limited. A traditional Chinese medicinal formula, Huangqin decoction (HQD), is chronicled in Shang Han Lun and is widely used to ameliorate gastrointestinal disorders, such as UC; however, its mechanism is yet to be clarified. PURPOSE: The present study aimed to investigate the effect of HQD on 7-day colitis induced by 3% dextran sulfate sodium (DSS) in mice and further explore the inhibitory effect of metabolites on DSS-damaged FHC cells. METHODS: The therapeutic efficacy of HQD was evaluated in a well-established DSS-induced colitis mice model. The clinical symptoms were analyzed, and biological samples were collected for microscopic examination, metabolomics, metagenomics, and the evaluation of the epithelial barrier function. The mechanism of metabolites regulated by HQD was evaluated in the DSS-induced FHC cell damage model. The samples were collected to detect the physiological functions of the cells. RESULTS: HQD suppressed the inflammation of DSS-induced colitis in vivo, attenuated DSS-induced clinical manifestations, reversed colon length reduction, and reduced histological injury. After HQD treatment, the DSS-induced gut dysbiosis was modulated, and the gut microbiota achieved a new equilibrium state. In addition, HQD activated the mTOR signaling pathway by upregulating amino acid metabolism. Significant phosphorylation of S6 and 4E-BP1 ameliorated intestinal epithelial barrier dysfunction. Moreover, HQD-regulated metabolites protected the epithelial barrier integrity by inhibiting DSS-induced apoptosis of FHC cells and regulating the proteins affecting apoptosis and cell-cell junction. CONCLUSIONS: These findings indicated that the mechanism of HQD was related to regulating the gut microbiota and amino acid metabolism, activating the mTOR signaling pathway, and protecting the intestinal mucosal barrier integrity.

Abnormal regional spontaneous neural activity in treatment-refractory depression revealed by resting-state fMRI.

Treatment-refractory depression (TRD) represents a large proportion of the depressive population, yet has seldom been investigated using advanced imaging techniques. To characterize brain dysfunction in TRD, we performed resting-state functional MRI (rs-fMRI) on 22 TRD patients, along with 26 matched healthy subjects and 22 patients who were depressed but not treatment-refractory (NDD) as comparison groups. Results were analyzed using a data-driven approach known as Regional Homogeneity (ReHo) analysis which measures the synchronization of spontaneous fMRI signal oscillations within spatially neighboring voxels. Relative to healthy controls, both depressed groups showed high ReHo primarily within temporo-limbic structures, and more widespread low ReHo in frontal, parietal, posterior fusiform cortices, and caudate. TRD patients showed more cerebral regions with altered ReHo than did NDD. Moderate but significant correlations between the altered regional ReHo and measures of clinical severity were observed in some identified clusters. These findings shed light on the pathophysiological mechanisms underlying TRD and demonstrate the feasibility of using ReHo as a research and clinical tool to monitor persistent cerebral dysfunction in depression, although further work is necessary to compare different measures of brain function to elucidate the neural substrates of these ReHo abnormalities.

Altered thalamocortical functional connectivity by propofol anesthesia in rats.

Anesthesia, a state of profound central nervous system suppression, involves a sequence of events that is still not well understood. In the present study, we examined the action of propofol (a sedative-hypnotic drug commonly used as anesthetic) on thalamocortical functional connectivity in rats by using functional connectivity magnetic resonance imaging (fcMRI) with a 3.0-tesla MR scanner. Intraperitoneal injections of propofol (80 or 160 mg/kg) were administered to Sprague-Dawley rats. Synchronized low-frequency fluctuations (LFF) of blood oxygen level-dependent (BOLD) signals were found between the thalamic and somatosensory cortices (S1/S2) after administration of 80 mg/kg propofol. However, after application of 160 mg/kg propofol, synchronized LFF of BOLD signals disappeared. These observations indicate that thalamocortical connectivity may play an important role in propofol anesthesia. We also observed that regionally specific long-range correlations of spontaneous low-frequency physiological fluctuations in BOLD signals may be present across somatosensory networks of the brain in the absence of external stimulation. However, our experiment suggests that fcMRI can be used to investigate brain networks that exhibit correlated fluctuations.

[Study on resting-state default mode network in patients with posttraumatic stress disorder after the earthquake].

OBJECTIVE: To explore the pathogenesis of posttraumatic stress disorder (PTSD) by studying default mode network during the resting state in patients with PTSD after homologous traumatic experience. METHODS: Seventeen PTSD patients and 20 matched normal controls received the examnation of resting-state fMRI scanning. Left and right posterior cingulate cortex was regarded as seed region respectively, and the functional connectivity about whole brain was assessed by using resting-state functional connectivity analysis. RESULTS: Compared with control group, the patients with PTSD showed that the brain area with decreased functional connectivity included left superior frontal gyrus and right fusiform gyrus, while the brain area with increased functional connectivity included right precuneus, right superior temporal gyrus and right middle temporal gyrus. CONCLUSION: The brain default mode network of PTSD patients is abnormal in resting state. These abnormalities might be the neuropathological mechanisms of PTSD.

Therapeutic effect of oxyberberine on obese non-alcoholic fatty liver disease rats.

BACKGROUND: Berberine (BBR) has been widely used to treat non-alcoholic fatty liver disease (NAFLD). The metabolites of BBR were believed to contribute significantly to its pharmacological effects. Oxyberberine (OBB), a gut microbiota-mediated oxidative metabolite of BBR, has been firstly identified in our recent work. PURPOSE: Here, we aimed to comparatively investigate the anti-NAFLD properties of OBB and BBR. METHODS: The anti-NAFLD effect was evaluated in high-fat diet-induced obese NAFLD rats with biochemical/ELISA tests and histological staining. The related gene and protein expressions were detected by qRT-PCR and Western blotting respectively. Molecular docking and dynamic simulation were also performed to provide further insight. RESULTS: Results indicated OBB remarkably and dose-dependently attenuated the clinical manifestations of NAFLD, which (100 mg/kg) achieved similar therapeutic effect to metformin (300 mg/kg) and was superior to BBR of the same dose. OBB significantly inhibited aberrant phosphorylation of IRS-1 and up-regulated the downstream protein expression and phosphorylation (PI3K, p-Akt/Akt and p-GSK-3ß/GSK-3ß) to improve hepatic insulin signal transduction. Meanwhile, OBB treatment remarkably alleviated inflammation via down-regulating the mRNA expression of MCP-1, Cd68, Nos2, Cd11c, while enhancing Arg1 mRNA expression in white adipose tissue. Moreover, OBB exhibited closer affinity with AMPK in silicon and superior hyperphosphorylation of AMPK in vivo, leading to increased ACC mRNA expression in liver and UCP-1 protein expression in adipose tissue. CONCLUSION: Taken together, compared with BBR, OBB was more capable of maintaining lipid homeostasis between liver and WAT via attenuating hepatic insulin pathway and adipocyte inflammation, which was associated with its property of superior AMPK activator.

Effects of Huangqin Decoction on ulcerative colitis by targeting estrogen receptor alpha and ameliorating endothelial dysfunction based on system pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin Decoction (HQD), a traditional Chinese medicinal (TCM) formula chronicled in Shang Han Lun, has been used to treat gastrointestinal diseases for nearly 1800 years. OBJECTIVE: To investigate the effects and underlying mechanisms of HQD on ulcerative colitis (UC). METHODS: The bioactive compounds in HQD were obtained from the traditional Chinese medicine systems pharmacology database. Then, the HQD and UC-related targets were analyzed by establishing HQD-Compounds-Targets (H-C-T) and protein-protein interaction (PPI) networks. Enrichment analysis was used for further study. The candidate targets for the effects of HQD on UC were validated using a dextran sulfate sodium-induced UC mouse experiment. RESULTS: The results showed that 51 key targets were gained by matching 284 HQD-related targets and 837 UC-related targets. Combined with H-C-T and PPI network analyses, the key targets were divided into endothelial growth, inflammation and signal transcription-related targets. Further experimental validation showed that HQD targeted estrogen receptor alpha (ESR1) and endothelial growth factor receptors to relieve endothelial dysfunction, thereby improving intestinal barrier function. The expression of inflammatory cytokines and signal transducers was suppressed by HQD treatment and inflammation was inhibited. CONCLUSIONS: HQD may acts on UC via the regulation of targets and pathways related to improving the intestinal mucosal barrier and ameliorating endothelial dysfunction. Additionally, ERS1 may be a new target to explore the mechanisms of UC.

Localization of cerebral functional deficits in treatment-naive, first-episode schizophrenia using resting-state fMRI.

BACKGROUND: Spontaneous low-frequency fluctuations (LFF) in the blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal have been shown to reflect cerebral spontaneous neural activity, and the present study attempts to explore the functional changes in the regional brain in patients with schizophrenia using the amplitude of the BOLD signals. METHODS: A total of 66 treatment-naïve, first-episode schizophrenia (FES) patients and 66 normal age- and sex-matched controls were recruited. Resting-state fMRIs were obtained using a gradient-echo echo-planar imaging sequence. The amplitude of LFF (ALFF) was calculated using REST software. Voxel-based analysis of the ALFF maps between control and patient groups was performed with twos-sample t-tests using SPM2. RESULTS: Compared to the controls, the FES group showed significantly decreased ALFF in the medial prefrontal lobe (MPFC) and significant increases in the ALFF in the left and right putamen. Significant positive correlations were observed between ALFF values in the bilateral putamen in both the patient and control groups. CONCLUSIONS: Alterations of the ALFF in the MPFC and putamen in FES observed in the present study suggest that the functional abnormalities of those areas are at an early stage of the disease.

[Microstructural abnormalities of basal ganglia and thalamus in children with first-episode Tourette's syndrome: a diffusion tensor imaging study].

OBJECTIVE: To investigate the microstructural integrity of basal ganglia and thalamus in children with first episode drug-naive Tourette's syndrome (TS) by diffusion tensor imaging (DTI). METHODS: Ten right handed patients with TS (mean age = 8.1 +/- 2.7 years old, 7 males and 3 females) and 10 age and gender-matched healthy control subjects (mean age = 9.5 +/- 1.6 years old, 9 males and 1 female) were recruited. All of the participants had normal findings on conventional MRI. DTI was performed using a 3.0T MR scanner by employing a spin echo single-shot EPI sequence with 15 diffusion encoding directions. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps were generated from each participant's DTI images using DTIStudio software. Bilateral regions of interest (ROI) for the caudate nucleus, putamen,globus pallidus and thalamus were manually traced through ROIEditor software on averaged DWI maps. The differences on DT-MRI variables (ADC, FA) between the two groups were compared using the SPSS13.0 software. Significance level was set at 0.05. RESULTS: Significant decrease in FA values in left globus pallidus and bilateral thalamus, and increase in ADC values in the bilateral caudate nucleus, bilateral putamen and bilateral thalamus were found in the children with TS compared with the normal controls. CONCLUSION: The results support the hypothesis of abnormalities in basal ganglia and thalamus in the pathophysiology of TS.

Vesselplasty using the Mesh-Hold™ bone-filling container for the treatment of pathological vertebral fractures due to osteolytic metastases: A retrospective study.

PURPOSE: To evaluate the clinical benefits and complications of vesselplasty using the Mesh-Hold™ bone-filling container in the treatment of vertebral osteolytic fractures. METHODS: This was a retrospective study of patients with vertebral osteolytic pathological fractures treated by vesselplasty at Sichuan Cancer Hospital between 09/2014 and 01/2018. VAS1 (Visual analog scale) scores and ODI2 (Oswestry disability index) were recorded routinely 1 day preoperative, at 1 day, 1 month, 3 months, 6 months, and 1 year postoperation, and at the last follow-up. V13 (The of bone cement injection volume) and V24 (vertebral body osteolytic volume) were evaluated, and the R5 (ratio) of bone cement filling was obtained according to the V1/V2. RESULTS: Sixty-three patients were included (105 segments with osteolytic fractures). The amount of bone cement for each vertebra was 2.4-5.2 ml (3.1 ± 0.7 ml). The ratio (R) of bone cement filling was not related to pain relief or functional recovery (all P > 0.05).The VAS scores and ODI at different time points after surgery were decreased compared with before surgery (all P < 0.05). The bone cement leakage rate was 16.2 % (17/105). The follow-up was 4-30 months (mean of 13 ± 6 months). Thirty patients had died by the last follow-up, all from their cancer. CONCLUSIONS: The Mesh-Hold™ bone-filling container in the treatment of vertebral fractures induced by osteolytic metastases could reduce pain, improve function, and reduce the bone cement leakage rate in the process of vesselplasty.

Therapeutic effect of Brucea javanica oil emulsion on experimental Crohn's disease in rats: Involvement of TLR4/ NF-κB signaling pathway.

Brucea javanica is an important Chinese folk medicine traditionally used for the treatment of dysentery (also known as inflammatory bowel diseases). Brucea javanica oil emulsion (BJOE), the most common preparation of Brucea javanica, has a variety of pharmacological activities. In this follow-up investigation, we endeavored to illuminate the potential benefit of BJOE on 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced Crohn's disease (CD) in rats and decipher the mechanism of action. The result illustrated that BJOE treatment significantly reduced the body weight loss, disease activity index and macroscopic scores, ameliorated shortening of colon length, arrested colonic histopathological deteriorations, lowered the histological scores in parallel to the model group. Furthermore, BJOE also decreased the levels of MPO and pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-17, IL-23 and IFN-γ), and increased the levels of anti-inflammatory cytokines (IL-4, IL-10 and TGF-ß) as compared with the model group. In addition, the elevated mRNA expression of MMP-1, MMP-3 and RAGE induced by TNBS was remarkably inhibited by BJOE, SASP or AZA treatments, while the mRNA expression of PPAR-γ was significantly enhanced. Furthermore, the activation of TLR4/NF-κB signaling pathway was significantly inhibited by AZA and BJOE treatment when compared with that of TNBS-treated rats. Our study suggested that BJOE exerted superior therapeutic effect to SASP and AZA in treating TNBS-induced colitis in rats. The protective effect of BJOE may involve the inhibition of the TLR4/NF-κB-mediated inflammatory responses. These results indicated that BJOE held promising potential to be further developed into a novel candidate for the treatment of CD.

Anti-Inflammatory Effects of Huangqin Decoction on Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice Through Regulation of the Gut Microbiota and Suppression of the Ras-PI3K-Akt-HIF-1α and NF-κB Pathways.

OBJECTIVE: Huangqin decoction (HQD), a classical traditional Chinese medicinal formula, has been commonly used to treat gastrointestinal diseases for thousands of years. We investigated the anti-inflammatory effects and underlying mechanisms of HQD on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC). METHODS: Experimental mice were given 3% DSS, and HQD (2.275, 4.55, and 9.1 g/kg), or mesalazine (ME, 200 mg/kg) orally for 7 days. Body weight loss, disease activity index (DAI), colon length, histology, and levels of inflammatory cytokines were measured to evaluate the effects of HQD on colitis. The effects of HQD on the Ras-phosphoinositide-3-kinase (PI3K)-Akt-hypoxia inducible factor 1 alpha (HIF-1α) and nuclear factor-kappa B (NF-κB) pathways were evaluated by Western blot analysis. In addition, the gut microbiota was characterized using high-throughput Illumina MiSeq sequencing. RESULTS: The results showed that HQD significantly reduced the body weight loss, ameliorated DAI, restored colon length, and improved the intestinal epithelial cell barrier in mice with DSS-induced colitis. The messenger RNA (mRNA) expression levels of inflammatory mediators were decreased following HQD treatment. Furthermore, the Ras-PI3K-Akt-HIF-1α and NF-κB pathways were significantly inhibited by HQD. Finally, treatment with HQD resulted in recovery of gut microbiota diversity. CONCLUSIONS: HQD ameliorates DSS-induced colitis through regulation of the gut microbiota, and suppression of Ras-PI3K-Akt-HIF-1α and NF-κB pathways. Our results suggested that HQD may be a potential candidate for treatment of UC.