Association of Longitudinal Changes in Cerebral Microstructure with Cognitive Functioning in Breast Cancer Survivors after Adjuvant Chemotherapy.

Background: Adjuvant chemotherapy for breast cancer might impact cognitive function and brain structure. Methods: In this study, we investigated the cerebral microstructural changes in breast cancer survivors after adjuvant chemotherapy and the correlation with cognitive function with both cross-sectional and longitudinal study designs. All participants underwent structural MRI. In total, we recruited 67 prechemotherapy patients (BB), 67 postchemotherapy patients (BA), and 77 healthy controls (BH). For the follow-up study, 28 participants in the BH and 28 in the BB groups returned for imaging and assessment (BHF, BBF). Voxel-based morphometry analysis was performed to evaluate differences in brain volume; vertex-based shape analysis was used to assess the shape alterations of subcortical regions. Moreover, multiple regression was applied to assess the association between the changes in neuropsychological assessment and brain volume. Results: The results showed brain volume reduction in the temporal and parietal gyrus in BB and BA patients. Among each group, we also found significant shape alterations in the caudate and thalamus. Volume reductions in the temporal regions and shape changes in the caudate and hippocampus were also observed in patients from time point 1 to time point 2 (postchemotherapy). An association between brain volume and cognitive performance was also found in the limbic system. Conclusions: Based on our findings, we can provide a better understanding of the cerebral structural changes in breast cancer survivors, establish a subsequent prediction model, and serve as a reference for subsequent treatment.

Work performance and its clinical correlates in patients with chronic mental illness: The Chinese version of Vocational Cognitive Rating Scale and the work behavior inventory.

OBJECTIVE: Occupational function assessment is essential for rehabilitation of severe mental illness but lacks comprehensive tools. METHOD: This study examines the psychometric properties of the Chinese versions of the Vocational Cognitive Rating Scale (VCRS) and the Work Behavior Inventory (WBI) in 60 chronic patients from a psychiatric daycare center and identifies clinical correlates of occupational function measured on the Positive and Negative Syndrome Scale (PANSS). RESULTS: The Chinese VCRS and WBI showed adequate internal consistency, interrater and test-retest reliability, and good convergent validity with the Comprehensive Occupational Therapy Evaluation Scale. Factor analysis favored a one-factor solution of the VCRS; and a four-factor structure in the WBI including Efficiency, Social Interaction, Appropriateness, and Regularity. The VCRS and Efficiency were predicted by fewer disorganization but greater affective symptoms. Social Interaction was negatively predicted by resistance symptoms. Appropriateness was associated with all but negative symptoms. Regularity was predicted by fewer negative symptoms. Considering work behavior altogether, WBI total scores were predicted by fewer negative, fewer disorganization, and greater affective symptoms. CONCLUSIONS AND IMPLICATION FOR PRACTICE: Findings suggest that the Chinese VCRS and WBI have sound psychometric properties and are suitable for both clinical trials and for planning personalized rehabilitation programs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Combined VEGF and bFGF loaded nanofiber membrane protects against neuronal injury and hypomyelination in a rat model of chronic cerebral hypoperfusion.

Currently, there are no effective therapeutic targets for the treatment of chronic cerebral hypoperfusion(CCH)-induced cerebral ischemic injury. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are discovered as the inducers of neurogenesis and angiogenesis. We previously made a nanofiber membrane (NFM), maintaining a long-term release of VEGF and bFGF up to 35 days, which might make VEGF and bFGF NFM as the potential protective agents against cerebral ischemic insult. In this study, the effects of VEGF and bFGF delivered by NFM into brain were investigated as well as their underlying mechanismsin a rat model of CCH. VEGF + bFGF NFM application increased the expressions of tight junction proteins, maintained BBB integrity, and alleviated vasogenic cerebral edema. Furthermore, VEGF + bFGF NFM sticking enhanced angiogenesis and elevated CBF. Besides, VEGF + bFGF NFM treatment inhibited neuronal apoptosis and decreased neuronal loss. Moreover, roofing of VEGF + bFGF NFM attenuated microglial activation and blocked the launch of NLRP3/caspase-1/IL-1ß pathway. In addition, VEGF + bFGF NFM administration prevented disruption to the pre/postsynaptic membranes and loss of myelin sheath, relieving synaptic injury and demyelination. Oligodendrogenesis, neurogenesis and PI3K/AKT/mTOR pathway were involved in the treatment of VEGF + bFGF NFM against CCH-induced neuronal injury and hypomyelination. These findings supported that VEGF + bFGF NFM application constitutes a neuroprotective strategy for the treatment of CCH, which may be worth further clinical translational research as a novel neuroprotective approach, benifiting indirect surgical revascularization.

Fecal microbiota transplantation and short-chain fatty acids protected against cognitive dysfunction in a rat model of chronic cerebral hypoperfusion.

AIMS: Clear roles and mechanisms in explaining gut microbial dysbiosis and microbial metabolites short-chain fatty acids (SCFAs) alterations in chronic cerebral ischemic pathogenesis have yet to be explored. In this study, we investigated chronic cerebral hypoperfusion (CCH)-induced gut microbiota and metabolic profiles of SCFAs as well as the effects and mechanisms of fecal microbiota transplantation (FMT) and SCFAs treatment on CCH-induced hippocampal neuronal injury. METHODS: Bilateral common carotid artery occlusion (BCCAo) was used to establish the CCH model. Gut microbiota and SCFAs profiles in feces and hippocampus were evaluated by 16S ribosomal RNA sequencing and gas chromatography-mass spectrometry. RNA sequencing analysis was performed in hippocampal tissues. The potential molecular pathways and differential genes were verified through western blot, immunoprecipitation, immunofluorescence, and ELISA. Cognitive function was assessed via the Morris water maze test. Ultrastructures of mitochondria and synapses were tested through a transmission electron microscope. RESULTS: Chronic cerebral hypoperfusion induced decreased fecal acetic and propionic acid and reduced hippocampal acetic acid, which were reversed after FMT and SCFAs administration by changing fecal microbial community structure and compositions. Furthermore, in the hippocampus, FMT and SCFAs replenishment exerted anti-neuroinflammatory effects through inhibiting microglial and astrocytic activation as well as switching microglial phenotype from M1 toward M2. Moreover, FMT and SCFAs treatment alleviated neuronal loss and microglia-mediated synaptic loss and maintained the normal process of synaptic vesicle fusion and release, resulting in the improvement of synaptic plasticity. In addition, FMT and SCFAs supplement prevented oxidative phosphorylation dysfunction via mitochondrial metabolic reprogramming. The above effects of FMT and SCFAs treatment led to the inhibition of CCH-induced cognitive impairment. CONCLUSION: Our findings highlight FMT and SCFAs replenishment would be the feasible gut microbiota-based strategy to mitigate chronic cerebral ischemia-induced neuronal injury.

VEGF loaded nanofiber membranes inhibit chronic cerebral hypoperfusion-induced cognitive dysfunction by promoting HIF-1a/VEGF mediated angiogenesis.

We investigated the potential effects and mechanisms of vascular endothelial growth factor (VEGF)-nanofiber membranes (NFMs) treatment in a rat model of chronic cerebral hypoperfusion (CCH). VEGF-NFMs treatment promoted angiogenesis in surgical temporal cortex and hippocampus, alleviating decreased CBF in these two cerebral regions. VEGF-NFMs application improved reduced NAA/Cr ratio, preventing neuronal loss. VEGF-NFMs sticking decreased the number of TUNEL-positive cells in surgical temporal cortex, ameliorated impaired synaptic plasticity, and inhibited the release of pro-inflammatory cytokines and the activation of microglia and astrocytes in surgical temporal cortex and hippocampus. Furthermore, BDNF-TrkB/PI3K/AKT, BDNF-TrkB/ERK and HIF-1a/VEGF/ERK pathways were involved in the treatment of VEGF-NFMs against CCH-induced neuronal injury. These results showed the neuroprotective effects of VEGF-NFMs sticking may initiate from neurovascular repairing followed by inhibition of neuronal apoptosis and neuronal and synaptic damage, eventually leading to the suppression of cognitive dysfunction, which provided theoretical foundation for further clinical transformation of VEGF-NFMs.

Fecal microbiota transplantation and replenishment of short-chain fatty acids protect against chronic cerebral hypoperfusion-induced colonic dysfunction by regulating gut microbiota, differentiation of Th17 cells, and mitochondrial energy metabolism.

BACKGROUND: Little is known about the association between gut microbiota and intestinal injury under a state of chronic cerebral hypoperfusion (CCH). Here, the effects of gut microbiota and short-chain fatty acids (SCFAs), as important metabolic products, on intestinal function and potential mechanisms after CCH were investigated. METHODS: Rats were subjected to bilateral common carotid artery occlusion (BCCAo) to induce CCH. The gut microbiota and metabolites of SCFAs were assessed by 16S rRNA sequencing and targeted metabolomics, respectively. Transcriptomic analysis of colon tissues was also conducted. Subsequently, potential molecular pathways and differentially expressed genes were verified by western blot, immunoprecipitation, and immunofluorescence analyses. Furthermore, the integrity of the colonic barrier was evaluated by hematoxylin and eosin and mucin 2 staining and expression levels of tight junction proteins. Besides, colonic inflammation was further assessed by flow cytometry and expression levels of inflammatory cytokines. In addition, colonic mitochondrial dysfunction was analyzed via membrane potential, reactive oxygen species, electron transport chain (ETC) activities, adenosine triphosphate content, and mitochondrial ultrastructure. RESULTS: CCH modified gut microbial composition and microbial metabolism of SCFAs, which may be associated with inhibition of mitochondrial ETC activities and oxidative phosphorylation, leading to dysregulation of mitochondrial energy metabolism. Furthermore, CCH induced differentiation of pathogenic Th17 cells, promoted the formation of complexes of interferon regulatory factor 4 and signal transducer and activator of transcription 3 (STAT3), and increased the phosphorylation of STAT3. This was associated with an impairment of colonic barrier function and chronic colonic inflammation. In contrast, FMT and SCFA replenishment ameliorated CCH-induced gut microbial dysbiosis by increasing the intestinal content of Ruminococcus_sp_N15_MGS_57 and modulating microbial metabolism of SCFAs by increasing acetic acid contents associated with an improvment of the balance between Tregs and Th17 cells, mitochondrial ETC activities, and oxidative phosphorylation to prevent colonic inflammation and dysregulation of mitochondrial energy metabolism. CONCLUSION: These findings indicate that FMT and SCFA replenishment present a promising therapeutic strategy against colonic dysfunction under a state of chronic cerebral ischemia.

The Impact of Hepatitis C Virus, Metabolic Disturbance, and Unhealthy Behavior on Chronic Kidney Disease: A Secondary Cross-Sectional Analysis.

BACKGROUND: Hepatitis C virus (HCV) infection is associated with a higher risk of chronic kidney disease (CKD). This study investigates the relationship among HCV, CKD, and understudied confounders, such as unhealthy behaviors and metabolic disturbances. METHODS: This cross-sectional study was conducted as part of a community health promotion program in an HCV endemic area of Taiwan from June to December 2019. Multivariable logistic regression analyses adjusted for demographic and clinical characteristics were performed to investigate the association between CKD and HCV seropositivity. RESULTS: Of 2387 participants who underwent health check-ups, the mean age was 64.1 years old; females predominated (63.2%), and 306 (12.8%) subjects were seropositive for HCV. CKD, defined as a lower estimated glomerular filtration rate (eGFR) was associated with unhealthy dietary habits, metabolic syndrome, and HCV. Less frequent exercise, higher waist circumference (WC) and HbA1c all affected risk of CKD; HCV increased risk of CKD by 44% compared to non-HCV (OR 1.44, 95% confidence interval (CI) 1.05-1.98) in the multivariable analysis. In the HCV group, lower eGFR was also significantly associated with the severity of metabolic syndrome (MetS) (median eGFR was 86.4, 77.1, and 64.5 mL/min/1.73 m2 for individuals with three and five MetS components, respectively). CONCLUSIONS: Beyond metabolic disturbance and irregular exercise, HCV seropositivity is independently associated with CKD in a community survey. Healthy lifestyle promotion might protect against renal function decline in HCV; however, the mechanisms underlying the association need further large-scale investigation.

A nationwide cohort investigation on pay-for-performance and major adverse limb events in patients with diabetes.

A retrospective cohort study was conducted using claims data from Taiwan's National Health Insurance program to assess the effect of diabetic pay-for-performance (P4P) program on major adverse limb events (MALE) and major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). This study included patients with T2DM who had completed or not completed a 1-year P4P program from 2002 to 2013. Propensity-score matching was used to balance the baseline characteristics between groups. The Cox proportional-hazard model and Fine and Gray subdistribution hazard model were used to examine the association between P4P and the risks of MALE, MACE, systemic thromboembolism (ST), heart failure (HF) hospitalization, and all-cause mortality. Patients who underwent the P4P program had a significantly decreased incidence of MALE (2.0% vs. 2.6%, subdistribution hazard ratio [SHR] 0.73, 95% CI 0.71-0.76). Regarding the individual components, the P4P group demonstrated lower risks for foot ulcer (1.1% vs 1.3%, SHR 0.80, 95% CI 0.77-0.84), gangrene (0.57% vs 0.93%, SHR 0.59, 95% CI 0.56-0.63), percutaneous transluminal angioplasty (0.61% vs 0.79%, SHR 0.72, 95% CI 0.68-0.77), and amputation (0.46% vs 0.75%, SHR 0.58, 95% CI 0.55-0.62). In addition, the risks of MACE, ST, HF hospitalization, and all-cause mortality were remarkably lower in the P4P group. The P4P program might significantly reduce critical events of MALE, MACE, ST, HF, and mortality in the diabetic population.

Effect of Xanthium Strumarium on HIV-1 5'-LTR Transcriptional Activity and Viral Reactivation in Latently Infected Cells.

Chinese herbal medicines (CHMs) are widely used in Asian countries. They show multiple pharmacological activities, including antiviral activities. The 5'-long terminal repeat (LTR) region of HIV-1, required for viral transcription, is a potential drug target for HIV-1 reactivation and intrinsic cell death induction of infected or latently infected cells. Modulation of HIV-1 reactivation requires interactions between host cell proteins and viral 5'-LTR elements. By evaluation of two CHMs- Xanthium strumarium and Pueraria montana, we found that 1) X. strumarium reactivated HIV-1 latently infected cells in J-Lat 8.4, J-Lat 9.2, U1, and ACH-2 cells in vitro; 2) 27 nuclear regulatory proteins were associated with HIV-1 5'-LTR using deoxyribonucleic acid affinity pull-down and LC-MS/MS analyses; and 3) among them, silencing of XRCC6 reactivated HIV-1 5'-LTR transcriptional activity. We found that X. strumarium inhibits the 5'-LTR associated XRCC6 nuclear regulatory proteins, increases its viral 5'-LTR promoter transcriptional activity, and reactivates HIV-1 latently infected cells in vitro. These findings may contribute to understanding the 5'-LTR activity and the host cell nuclear regulatory protein machinery for reactivating HIV-1 and for future investigations to eradicate and cure HIV-1 infection.

Preservation of spatial memory and neuroprotection by the fatty acid amide hydrolase inhibitor URB597 in a rat model of vascular dementia.

BACKGROUND: Chronic cerebral hypoperfusion (CCH) is a major risk factor for vascular dementia (VaD). There are currently no broadly effective prevention or treatment strategies for VaD, but recent studies have reported promising results following vascular bypass surgery and pharmacomodulation of the brain endocannabinoid system (ECS). In this study, early effects of encephalomyosynangiosis (EMS) bypass surgery and augmented endocannabinoid signaling on CCH-induced cognitive dysfunction and neuronal damage were investigated. METHODS: An animal model of VaD was established by bilateral common carotid artery occlusion (BCCAO). Cannabinoid signaling was upregulated by treatment with the fatty acid amide hydrolase inhibitor URB597 (URB). Spatial learning and memory, cerebral blood flow (CBF), revascularization, brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signaling, and apoptosis were compared among Sham, BCCAO, BCCAO + EMS, BCCAO + URB, and BCCAO + URB + EMS groups. Spatial learning and memory were evaluated using the Morris water maze (MWM). The CBF in cortex and hippocampus was evaluated by 3-dimensional arterial spin labeling. The neovascularization was visualized by CD34 immunofluorescence staining, and BDNF-TrkB signaling protein expression levels were assessed by Western blotting. RESULTS: Treatment with URB597 but not EMS alone reversed the spatial learning and memory deficits induced by BCCAO. Neovascularization was enhanced after EMS surgery but not by URB597. Alternatively, there were no significant differences in CBF among treatment groups. Expression levels of BDNF and TrkB were significantly reduced by CCH compared to Sham treatment, and downregulation of both proteins was reversed by URB597 treatment but not EMS. BCCAO enhanced neuronal apoptosis, which was also reversed by URB597. CONCLUSIONS: Augmentation of endogenous cannabinoid signaling but not EMS protects against CCH-induced neurodegeneration and preserves spatial learning and memory, possibly by activating BDNF-TrkB signaling.

The effect of pay-for-performance program on infection events and mortality rate in diabetic patients: a nationwide population-based cohort study.

BACKGROUND: Diabetes mellitus is a known risk factor for infection. Pay for Performance (P4P) program is designed to enhance the comprehensive patient care. The aim of this study is to evaluate the effect of the P4P program on infection incidence in type 2 diabetic patients. METHODS: This is a retrospective longitudinal cohort study using data from the National Health Insurance Research Database in Taiwan. Diabetic patients between 1 January 2002 and 31 December 2013 were included. Primary outcomes analyzed were patient emergency room (ER) infection events and deaths. RESULTS: After propensity score matching, there were 337,184 patients in both the P4P and non-P4P cohort. The results showed that patients' completing one-year P4P program was associated with a decreased risk of any ER infection event (27.2% vs. 29%; subdistribution hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.86-0.88). While the number needed to treat was 58 for the non-P4P group, it dropped to 28 in the P4P group. The risk of infection-related death was significantly lower in the P4P group than in the non-P4P group (4.1% vs. 7.6%; HR 0.46, 95% CI 0.45-0.47). The effect of P4P on ER infection incidence and infection-related death was more apparent in the subgroups of patients who were female, had diabetes duration ≥5 years, chronic kidney disease, higher Charlson's Comorbidity Index scores and infection-related hospitalization in the previous 3 years. CONCLUSIONS: The P4P program might reduce risk of ER infection events and infection-related deaths in type 2 diabetic patients.

Do initially non-dehydrated patients with acute ischemic stroke need fluid supplement?

Background: We previously found that dehydration is an independent predictor of early deterioration after acute ischemic stroke and rehydration helps to improve outcomes. There is limited evidence of how to treat patients who are initially non-dehydrated. In this study, we tested the hypothesis that rehydration therapy, based on the daily urine specific gravity, will improve the outcome of ischemic stroke patients who are initially non-dehydrated. Methods: We conducted a single-arm prospective study of patients with acute ischemic stroke with historical controls. For the first 5 days of study group, a daily urine specific gravity of > 1.020 g/ml was taken as indication for rehydration and patients were advised to drink water via oral or tubal feeding with a dose of 5 ml/kg body weight right away and after dinner. Control group patients were rehydrated without reference to urine specific gravity. An increase in National Institutes of Health Stroke Scale score of ≥ 4 within three days was defined as having stroke-in-evolution. Scores of ≤ 1 on the modified Rankin scale at 3 months were considered to indicate a favorable outcome. Results: A total of 125 patients were analyzed, 46 in the study group and 79 in the control group. The groups did not significantly differ in the stroke-in-evolution rate (4.3% vs. 8.2%, P = 0.474). The rate of favorable outcome at 3 months was significantly higher in the study group than in the control group (56.5% vs. 27.8%, P = 0.001). Conclusions: Urine specific gravity-based hydration might be a useful method to improve functional outcomes of patients with acute ischemic stroke who were non-dehydrated at admission.

Patients with Liver Cirrhosis as Frequent Attenders of Emergency Departments.

OBJECTIVES: Frequent attendance for nonemergency problems to emergency departments (EDs) contributes to ED overcrowding, resulting in medical care delays, increased medical errors, and social and economic burdens. Most studies regarding frequent attenders of EDs examine general patients without classifying certain subgroups. This study aimed to investigate patients with liver cirrhosis who present repeatedly to the ED. METHODS: This was a retrospective, observational cohort study of adult patients with a history of liver cirrhosis presenting to the ED from January 2011 to December 2015. We included patients with cirrhosis whose first ED visit occurred during the study period. We went far back for 20 years and excluded patients with any ED visits (including both cirrhosis and noncirrhosis-related ones) before the study period. We categorized frequent attenders as patients with more than 4 ED visits within 12 months after the first ED visit; infrequent attenders were those who did not meet this criterion. RESULTS: A total of 3513 patients with cirrhosis were included in this retrospective cohort study. Compared with the infrequent attenders, frequent attenders had a higher rate of presentations due to hepatic encephalopathy (15.2% vs 13.7%, P < 0.001) and ascites (10% vs 4%, P < 0.001) and ascites (10% vs 4%, P < 0.001) and ascites (10% vs 4%. CONCLUSIONS: Hepatic encephalopathy and ascites account for more ED visits in frequent than in infrequent attenders. Our findings provide information for those planning outpatient support for patients with cirrhosis. Further research is warranted.

Neuroprotective effects of andrographolide on chronic cerebral hypoperfusion-induced hippocampal neuronal damage in rats possibly via PTEN/AKT signaling pathway.

To explore the potential effects of andrographolide on chronic cerebral hypoperfusion (CCH)-induced neuronal damage as well as the underlying mechanisms. Rat CCH model was established by 2-vessel occlusion (2VO). The CCH rats received andrographolide treatment for 4 weeks. The neuron loss was detected by using neuronal nuclei (NeuN) immunofluorescent staining. The expression levels of phospho-phosphatase and tensin homolog deleted on chromosome ten (p-PTEN), protein kinase B (AKT), p-AKT, and cysteinyl aspartate specific proteinase-3 (Caspase-3) proteins were accessed by Western blotting. Moreover, the neuronal apoptosis of hippocampus tissues was detected via terminal deoxynucleotidyl transferase- mediated dUTP nick end labeling (TUNEL) staining. CCH reduced the number of NeuN-positive cells, while the number was significant increased after andrographolide treatment. CCH increased the proteins expression level of p-PTEN, Caspase-3, and decreased the p-AKT, which were reversed by andrographolide treatment. Furthermore, andrographolide treatment also down-regulated CCH-induced TUNEL-apoptosis rate. Our results suggest that the PTEN/AKT pathway may be modulated by andrographolide and the damaging effects of CCH on hippocampus may be ameliorated by andrographolide treatment. Andrographolide may act as a potential therapeutic approach for chronic ischemic insults.

URB597 protects against NLRP3 inflammasome activation by inhibiting autophagy dysfunction in a rat model of chronic cerebral hypoperfusion.

BACKGROUND: Previous studies reported that URB597 (URB) had therapeutic potential for treating chronic cerebral hypoperfusion (CCH)-induced neuroinflammation and autophagy dysfunction. However, the interaction mechanisms underlying the CCH-induced abnormal excessive autophagy and neuroinflammation remain unknown. In this study, we investigated the roles of impaired autophagy in nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing (NLRP) 3 inflammasome activation in the rat hippocampus and the underlying mechanisms under the condition of induced CCH as well as the effect of URB treatment. METHODS: The CCH rat model was established by bilateral common carotid artery occlusion (BCCAo), and rats were randomly divided into 11 groups as follows: (1) sham-operated, (2) BCCAo; (3) BCCAo+autophagy inhibitor 3-methyladenine (3-MA), (4) BCCAo+lysosome inhibitor chloroquine (CQ), (5) BCCAo+microglial activation inhibitor minocycline, (6) BCCAo+ROS scavenger N-acetylcysteine (NAC), (7) BCCAo+URB, (8) BCCAo+URB+3-MA, (9) BCCAo+URB+CQ, (10) BCCAo+URB+minocycline, (11) BCCAo+URB+NAC. The cell localizations of LC3, p62, LAMP1, TOM20 and NLRP3 were assessed by immunofluorescence staining. The levels of autophagy-related proteins (LC3, p62, LAMP1, BNIP3 and parkin), NLRP3 inflammasome-related proteins (NLRP3, CASP1 and IL-1ß), microglial marker (OX-42) and proinflammatory cytokines (iNOS and COX-2) were evaluated by western blotting, and proinflammatory cytokines (IL-1ß and TNF-a) were determined by ELISA. Reactive oxygen species (ROS) were assessed by dihydroethidium staining. The mitochondrial ultrastructural changes were examined by electron microscopy. RESULTS: CCH induced microglial overactivation and ROS accumulation, promoting the activation of the NLRP3 inflammasome and the release of IL-1ß. Blocked autophagy and mitophagy flux enhanced the activation of the NLRP3-CASP1 inflammasome pathway. However, URB alleviated impaired autophagy and mitophagy by decreasing mitochondrial ROS and microglial overactivation as well as restoring lysosomal function, which would further inhibit the activation of the NLRP3-CASP1 inflammasome pathway. CONCLUSION: These findings extended previous studies indicating the function of URB in the mitigation of chronic ischemic injury of the brain.

Efficacy of chemoradiotherapy versus radiation alone in patients with inoperable locally advanced non-small-cell lung cancer: A meta-analysis and systematic review.

BACKGROUND: This meta-analysis compared radiotherapy (RT) versus concurrent chemoradiotherapy (RT+CT) in treating patients with inoperable stage III non-small-cell lung cancer (NSCLC). METHODS: Medline, Cochrane, EMBASE, Google Scholar databases were searched until July 28, 2015 using the following keywords non-small cell lung cancer, advanced cancer, incurable/inoperable/unresectable, chemotherapy, radiotherapy, chemoradiotherapy/chemoradiation. Randomized controlled trials (RCTs) and two-armed prospective studies that compared combined RT+CT with RT alone in patients with locally advanced (stage III) nonresectable NSCLC were eligible for inclusion. Treatment effect on overall survival, progression-free survival (PFS), and objective response rate (ORR) were evaluated. RESULTS: Ultimately, 13 RCT studies were included in the systematic review and meta-analysis. The 13 studies included a total of 1936 patients with incurable/inoperable stage III NSCLC, of which 975 received RT alone and 961 received RT+CT combination therapy. The average age ranged from 54 to 77 years. At 1 and 2 years after treatment, the pooled data reveal that patients receiving CT+RT combination therapy had higher overall survival (pooled hazard ratio (HR), 0.72; 95% CI, 0.62-0.84; P < .001; 1-yr: HR, 0.67; 95% CI, 0.54-0.84; P < .001; 2-year: HR, 0.57; 95% CI, 0.45-0.73; P < .001), higher PFS (pooled HR, 0.73, 95% CI, 0.60-0.89; P = .002; 1-year: HR, 0.36; 95% CI, 0.24-0.53; P < .001; 2-year: HR, 0.38; 95% CI, 0.23-0.63; P < .001). CONCLUSION: Our findings show higher efficacy for concurrent CT+RT over RT alone in treating locally-advanced, unresectable stage III NSCLC.

Andrographolide enhances hippocampal BDNF signaling and suppresses neuronal apoptosis, astroglial activation, neuroinflammation, and spatial memory deficits in a rat model of chronic cerebral hypoperfusion.

Andrographolide is a medical herbal compound with documented anti-inflammatory activity and therapeutic efficacy in animal models of Alzheimer's disease, traumatic brain injury, and ischemic stroke. The present study examined the potential therapeutic effects of andrographolide on chronic cerebral hypoperfusion (CCH)-induced hippocampal neuronal damage and cognitive dysfunction. A CCH model was established in male Sprague Dawley (SD) rats using 2-vessel occlusion (2VO). After 4 weeks of CCH, spatial learning and memory were assessed in the Morris water maze and structural damage to the hippocampus by hematoxylin and eosin (HE) staining. Astrocyte activation was examined by immunohistochemical staining and Western blotting for glial fibrillary acid protein (GFAP), while expression levels of the pro-inflammatory cytokine-tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1ß), the apoptosis effector cysteinyl aspartate specific proteinase-3 (caspase-3), and the neuroprotectant brain-derived neurotrophic factor (BDNF) and the TrkB receptor were estimated by Western blotting. After 4 weeks of CCH, the hippocampus of 2VO rats exhibited marked neurodegeneration as well as elevated GFAP, TNF-α, IL-1ß, and caspase-3 compared to Sham controls. In addition, spatial learning was impaired compared to Sham controls. Andrographolide treatment during CCH suppressed astrocyte activation as evidenced by reduced GFAP expression, enhanced expression of BDNF and TrkB, improved impaired spatial learning and memory, and reversed upregulated TNF-α, IL-1ß, and caspase-3 expression. These results reveal a potential neuroprotective effect of andrographolide on hippocampal neuronal damage and cognitive impairment from CCH due to suppression of astrocyte activation and enhancement of BDNF-TrkB signaling.

Effects of Chinese herbal medicine therapy on survival and hepatic outcomes in patients with hepatitis C virus infection in Taiwan.

BACKGROUND: Chinese herbal medicine (CHM) is a complementary natural medicine that is used widely for the treatment of hepatic diseases. The aim of this study was to investigate the effects of the long-term use of CHM for the treatment of liver diseases, as prescribed by TCM doctors, on overall mortality and hepatic outcomes in patients with HCV. PATIENTS AND METHODS: We identified 98788 patients with HCV. Of these, 829 and 829 patients who were users and non-users of CHM, respectively, were matched for age, gender, CCI, and comorbidities prior to CHM treatment. The chi-squared test, Cox proportional hazard model, Kaplan--Meier method, and log-rank test were used for comparisons. RESULTS: CHM users had a lower risk of overall mortality than non-users after adjustment for comorbidities by using a multivariate Cox proportional hazard model (p-value < 0.001; HR: 0.12, 95% CI: 0.06-0.26). In addition,the CHM users had a lower risk of liver cirrhosis than non-users after adjustment for comorbidities (p-value = 0.028; HR: 0.29, 95% CI: 0.09-0.88). The 12-year cumulative incidences of overall mortality and liver cirrhosis were lower in the CHM group (p-value < 0.05 for both, log rank test). The CHM co-prescription for Dan-Shen, Bie-Jia, Jia-Wei-Xiao-Yao-San => E-Shu was found to occur most often associated for the specific treatment of HCV infection. CONCLUSION: CHM as adjunctive therapy may reduce the overall mortality and the risk of liver cirrhosis in patients with HCV. The comprehensive list of the herbal medicines that may be used for the treatment of patients with HCV may be useful in future scientific investigations or for future therapeutic interventions to prevent negative hepatic outcomes in patients with HCV.

Gender Differences and Work-Family Conflicts among Emergency Physicians with Intention to Leave.

BACKGROUNDS: The objective of this study was to investigate the relationships among intention to leave, emergency physician clinical activities, work-family conflicts, and gender differences in emergency physicians (EPs). METHODS: The survey instrument was a self-administered questionnaire containing basic demographic information and characteristics of clinical activities. The work-family conflicts were assessed by the Chinese version of the work-family conflict (WIF) scale. The questionnaires were mailed to board-certified EPs between January 2014 and August 2014. Student's t-test, Chi-square test, and one-way analysis of variance (ANOVA) were used to test the difference between subgroups. Logistic regression analysis was performed to determine the factors associated with intention to leave and gender differences. RESULTS: The study included 222 respondents for analysis after exclusions. Compared with physicians not planning to leave, those planning to leave ED practice showed higher dissatisfaction with their clinical work hours (50.0% versus 31.4%, p = 0.035) and night/day shift ratio (52.9% versus 31.0%, p = 0.013) and tended to work with night/day shift ratio exceeding 40% (67.6% versus 45.7%, p = 0.019). Female physicians were more likely to leave ED practice (females versus males, 26.5% versus 10.1%, p = 0.008). A significantly higher level of WIF scale was noted in the group with intention to leave ED practice (3.7 ± 0.6 versus 3.3 ± 0.7, p = 0.001). CONCLUSIONS: Females and EPs with higher level of WIF scale were more likely to leave emergency clinical practice. Instead of the number of clinical practice hours, the satisfaction with the clinical work hours and night shift frequency were significantly associated with the intention to leave.