Exploring tumor heterogeneity in colorectal liver metastases by imaging: Unsupervised machine learning of preoperative CT radiomics features for prognostic stratification.

OBJECTIVES: This study aimed to investigate tumor heterogeneity of colorectal liver metastases (CRLM) and stratify the patients into different risk groups of prognoses following liver resection by applying an unsupervised radiomics machine-learning approach to preoperative CT images. METHODS: This retrospective study retrieved clinical information and CT images of 197 patients with CRLM from The Cancer Imaging Archive (TCIA) database. Radiomics features were extracted from a segmented liver lesion identified at the portal venous phase. Those features which showed high stability, non-redundancy, and indicative information were selected. An unsupervised consensus clustering analysis on these features was adopted to identify subgroups of CRLM patients. Overall survival (OS), disease-free survival (DFS), and liver-specific DFS were compared between the identified subgroups. Cox regression analysis was applied to evaluate prognostic risk factors. RESULTS: A total of 851 radiomics features were extracted, and 56 robust features were finally selected for unsupervised clustering analysis which identified two distinct subgroups (96 and 101 patients respectively). There were significant differences in the OS, DFS, and liver-specific DFS between the subgroups (all log-rank p < 0.05). The subgroup with worse outcome using the proposed radiomics model was consistently associated with shorter OS, DFS, and liver-specific DFS, with hazard ratios of 1.78 (95 %CI: 1.12-2.83), 1.72 (95 %CI: 1.16-2.54), and 1.59 (95 %CI: 1.10-2.31), respectively. The general performance of this radiomics model outperformed the traditional Clinical Risk Score and Tumor Burden Score in the prognosis prediction after surgery for CRLM. CONCLUSION: Radiomics features derived from preoperative CT images can reveal the heterogeneity of CRLM and stratify the patients with CRLM into subgroups with significantly different clinical outcomes.

A novel dual polarization multiplexing RoF system integrating optical fiber and FSO channel with AMI downlink signals.

Using dual polarization multiplexing alternate mark inversion (AMI) downlink signals, a novel radio over fiber (RoF) system integrating optical fiber and FSO channel is designed to adapt to applications in mountainous areas and other complex terrain areas. Optical heterodyne technology and self-mixing homodyne detection method are used to realize high sensitivity detection of the received signals after 25.1 km channel (including 1 km single-mode fiber and 100 m free space link) transmission. Moreover, polarization multiplexing technology is introduced to exponentially increase the transmission capacity of downlink signals. This scheme not only can be compatible with traditional optical fiber transmission systems, but also support the wireless optical access application of millimeter wave signals in RoF systems.

Impact of body composition on the prognosis of hepatocellular carcinoma patients treated with transarterial chemoembolization: A systematic review and meta-analysis.

Objectives: To summarize current evidence about the influence of body composition on the prognosis of patients with hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) treatment. Methods: Public databases were systematically searched to identify relevant studies published from the inception of the database up to May 2023. Studies that evaluated the association between body composition and clinical outcomes in HCC patients who underwent TACE were included. A pre-designed table was applied to summarize relevant information. Meta-analysis was performed to estimate the association of body composition with overall survival. Results: Fourteen studies were included in this review, including 3631 patients (sample size range: 56-908, median 186). All body composition measurements (including skeletal muscle area, visceral and subcutaneous adipose area, and bone mineral density) were based on computer tomography. The commonly used parameter was skeletal muscle index at 3rd lumbar vertebra level (8/14). Three studies evaluated the correlations of body composition changes with the prognosis after TACE. Most studies (12/14) identified body composition parameters as an independent indicator for overall survival, progression-free survival, and treatment response rate. The hazard ratio of different body composition parameters ranged from 1.01 to 2.88, and hazard ratio of body composition changes ranged from 1.88 to 5.93. The pooled hazard ratio of sarcopenia for overall survival was 1.38 (95 %CI: 1.20-1.58). Conclusions: Body composition seems to be an important prognostic factor for a poorer clinical outcome after TACE treatment in patients with hepatocellular carcinoma. Future prospective studies with a larger sample size are required to confirm these findings. Registration study: This study has been prospectively registered at the PROSPERO platform (https://www.crd.york.ac.uk/prospero/) with the registration No. CRD42022345602.

Glycemic variability correlates with medial temporal lobe atrophy and decreased cognitive performance in patients with memory deficits.

Background: In the past, researchers have observed a significant link between glycemia and dementia. Medial temporal atrophy (MTA) is regarded as a common marker of dementia. The correlation between glycemic variability and MTA is unclear, and it has not been determined whether glycemic variability can be utilized as a biomarker of MTA and cognitive performance. Methods: The patients in a memory clinic who underwent brain MRI scans and cognitive assessments within the first week of their hospital visit, were enrolled. All participants underwent three fasting blood glucose and one HBA1c assessments on three self-selected days within 1 week of their first visit. The variability independent of the mean (VIM) was employed. Validated visual scales were used to rate the MTA results. The mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA) scales were employed to assess the cognitive functions of the participants. Spearman's correlation and regression models were used to examine the relationship between the MMSE and MoCA scales, and also determine the link between the MRI characteristics and cognitive status, where vascular risk factors, educational status, age, gender, and mean glucose parameters served as covariates. Results: Four hundred sixty-one subjects completed the MMSE scale, while 447 participants completed the MoCA scale. Data analysis revealed that 47.72% of the participants were men (220/461), and the median age of the patients was 69.87 ± 5.37 years. The findings of Spearman's correlation analysis exhibited a strong negative relationship between the VIM and MMSE score (r = -0.729, P < 0.01), and the MoCA score (r = -0.710, P < 0.01). The VIM was regarded as an independent risk factor for determining cognitive impairment in both the MMSE and MoCA assessments. The results were unaffected by sensitivity analysis. In addition, a non-linear relationship was observed between the VIM and MTA scores. Conclusion: The variability in the blood glucose levels, which was presented as VIM, was related to the reduced cognitive function, which was reflected by MMSE and MoCA scales. The relationship between the VIM and the MTA score was non-linear. The VIM was positively related to the MTA score when the VIM was less than 2.42.

Radiomics models for preoperative prediction of the histopathological grade of hepatocellular carcinoma: A systematic review and radiomics quality score assessment.

OBJECTIVE: To systematically review the efficacy of radiomics models derived from computed tomography (CT) or magnetic resonance imaging (MRI) in preoperative prediction of the histopathological grade of hepatocellular carcinoma (HCC). METHODS: Systematic literature search was performed at databases of PubMed, Web of Science, Embase, and Cochrane Library up to 30 December 2022. Studies that developed a radiomics model using preoperative CT/MRI for predicting the histopathological grade of HCC were regarded as eligible. A pre-defined table was used to extract the data related to study and patient characteristics, characteristics of radiomics modelling workflow, and the model performance metrics. Radiomics quality score and the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) were applied for research quality evaluation. RESULTS: Eleven eligible studies were included in this review, consisting of 2245 patients (range 53-494, median 165). No studies were prospectively designed and only two studies had an external test cohort. Half of the studies (five) used CT images and the other half MRI. The median number of extracted radiomics features was 328 (range: 40-1688), which was reduced to 11 (range: 1-50) after feature selection. The commonly used classifiers were logistic regression and support vector machine (both 4/11). When evaluated on the two external test cohorts, the area under the curve of the radiomics models was 0.70 and 0.77. The median radiomics quality score was 10 (range 2-13), corresponding to 28% (range 6-36%) of the full scale. Most studies showed an unclear risk of bias as evaluated by QUADAS-2. CONCLUSION: Radiomics models based on preoperative CT or MRI have the potential to be used as an imaging biomarker for prediction of HCC histopathological grade. However, improved research and reporting quality is required to ensure sufficient reliability and reproducibility prior to implementation into clinical practice.

Application of Shouwu Yizhi prescription in decubation of patients with ischemic stroke.

We investigate the application of Shouwu Yizhi prescription (SYP) in decubation of patients with ischemic stroke (IS). The clinical data of 106 patients recovering from IS who came to our hospital from December 2019 to December 2020 were selected for retrospective analysis, and they were separated into experimental group (n = 53, basic treatment + SYP) and control group (n = 53, basic treatment) based on the principle of random grouping. The clinical indexes such as lipid indexes and neurological disability score (NDS) after treatment were compared between both groups to comprehensively evaluate the clinical effects of different treatment regimens. Except for high-density lipoprotein cholesterol value, the lipid indexes in the experimental group after treatment were remarkably lower than those in the control group (P < 0.001). After treatment, the levels of hypersensitive C-reactive protein, homocysteine and lipoprotein-associated phospholipase A2 were remarkably lower in the experimental group than control group (P < 0.05). After treatment, the experimental group had remarkably higher mean scores of Montreal Cognitive Assessment, Fugl-Meyer Assessment in upper and lower limbs and lower NDS than control group (P < 0.001). SYP is an efficient treatment plan in decubation of IS, which can effectively improve the blood lipid indexes and neurological function of patients, and further studies will help establish a better solution for such patients.

Polysaccharides from Panax ginseng promote intestinal epithelial cell migration through affecting the Ca2+ related regulators.

Background and aim: Panax ginseng, a key herbal medicine of replenishing Qi and tonifying Spleen, is widely used in the treatment of gastrointestinal diseases in East Asia. In this study, we aim to investigate the potential effects and mechanisms of polysaccharides from P. ginseng (PGP) on intestinal mucosal restitution which is one of the crucial repair modalities during the recovery of mucosal injury controlled by the Ca2+ signaling. Methods: Rat model of intestinal mucosal injury was induced by indomethacin. The fractional cell migration was carried out by immunohistochemistry staining with BrdU. The morphological observations on intestinal mucosal injury were also performed. Intestinal epithelial cell (IEC-6) migration in vitro was conducted by scratch method. Western-blot was adopted to determine the expressions of PLC-γ1, Rac1, TRPC1, RhoA and Cav-1. Immunoprecipitation was used to evaluate the levels of Rac1/PLC-γ1, RhoA/TRPC1 and Cav-1/TRPC1. Results: The results showed that PGP effectively reduced the assessment of intestinal mucosal injury, reversed the inhibition of epithelial cell migration induced by Indomethacin, and increased the level of Ca2+ in intestinal mucosa in vivo. Moreover, PGP dramatically promoted IEC-6 cell migration, the expression of Ca2+ regulators (PLC-γ1, Rac1, TRPC1, Cav-1 and RhoA) as well as protein complexes (Rac1/PLC-γ1, Cav-1/TRPC1 and RhoA/TRPC1) in vitro. Conclusion: PGP increases the Ca2+ content in intestinal mucosa partly through controlling the regulators of Ca2+ mobilization, subsequently promotes intestinal epithelial cell migration, and then prevents intestinal mucosal injury induced by indomethacin.

Systematic review of machine learning-based radiomics approach for predicting microsatellite instability status in colorectal cancer.

This study aimed to systematically summarize the performance of the machine learning-based radiomics models in the prediction of microsatellite instability (MSI) in patients with colorectal cancer (CRC). It was conducted according to the preferred reporting items for a systematic review and meta-analysis of diagnostic test accuracy studies (PRISMA-DTA) guideline and was registered at the PROSPERO website with an identifier CRD42022295787. Systematic literature searching was conducted in databases of PubMed, Embase, Web of Science, and Cochrane Library up to November 10, 2022. Research which applied radiomics analysis on preoperative CT/MRI/PET-CT images for predicting the MSI status in CRC patients with no history of anti-tumor therapies was eligible. The radiomics quality score (RQS) and Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) were applied to evaluate the research quality (full score 100%). Twelve studies with 4,320 patients were included. All studies were retrospective, and only four had an external validation cohort. The median incidence of MSI was 19% (range 8-34%). The area under the receiver operator curve of the models ranged from 0.78 to 0.96 (median 0.83) in the external validation cohort. The median sensitivity was 0.76 (range 0.32-1.00), and the median specificity was 0.87 (range 0.69-1.00). The median RQS score was 38% (range 14-50%), and half of the studies showed high risk in patient selection as evaluated by QUADAS-2. In conclusion, while radiomics based on pretreatment imaging modalities had a high performance in the prediction of MSI status in CRC, so far it does not appear to be ready for clinical use due to insufficient methodological quality.

Impact of sarcopenia on the future liver remnant growth after portal vein embolization and associating liver partition and portal vein ligation for staged hepatectomy in patients with liver cancer: A systematic review.

Purpose: The impact of sarcopenia on the future liver remnant (FLR) growth after portal vein occlusion, including portal vein embolization (PVE) and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has gained increasing interest. This systematic review aimed to explore whether sarcopenia was associated with insufficient FLR growth after PVE/ALPPS stage-1. Methods: A systematic literature search was performed in PubMed, Embase, Web of Science, and Cochrane Library up to 05 July 2022. Studies evaluating the influence of sarcopenia on FLR growth after PVE/ALPPS stage-1 in patients with liver cancer were included. A predefined table was used to extract information including the study and patient characteristics, sarcopenia measurement, FLR growth, post-treatment complications and post-hepatectomy liver failure, resection rate. Research quality was evaluated by the Newcastle-Ottawa Scale. Results: Five studies consisting of 609 patients were included in this study, with a sample size ranging from 42 to 306 (median: 90) patients. Only one study was multicenter research. The incidence of sarcopenia differed from 40% to 67% (median: 63%). Skeletal muscle index based on pretreatment computed tomography was the commonly used parameter for sarcopenia evaluation. All included studies showed that sarcopenia impaired the FLR growth after PVE/ALPPS stage-1. However, the association between sarcopenia and post-treatment complications, post-hepatectomy liver failure, and resection rate remains unclear. All studies showed moderate-to-high quality. Conclusions: Sarcopenia seems to be prevalent in patients undergoing PVE/ALPPS and may be a risk factor for impaired liver growth after PVE/ALPPS stage-1 according to currently limited evidence. Systematic review registration: https://inplasy.com/, identifier INPLASY202280038.

Comparative study of Janus B2XY (X, Y = S, Se, Te) and F-BNBN-H monolayers for water splitting: revealing the positive and negative roles of the intrinsic dipole.

It is widely recognized that the intrinsic dipole in two-dimensional (2D) photocatalysts promotes hydrogen production during water splitting. Herein, we wonder whether the intrinsic dipole plays a negative role in water splitting. In this work, we make a comparative study of the structural, electronic, and photocatalytic properties of Janus B2XY (X, Y = S, Se, Te) and F-BNBN-H monolayers using first principles. Our theoretical results reveal that both B2XY and F-BNBN-H monolayers exhibit spatially separated conduction band minimum (CBM) and valence band maximum (VBM), as well as vacuum level differences at the opposite surfaces due to the intrinsic dipole. The F-BNBN-H monolayer has excellent redox ability for water splitting, because its CBM is located at the surface with a lower vacuum level and its VBM is distributed on the opposite surface possessing a higher vacuum level. By sharp contrast, B2XY monolayers have limited or vanishing redox ability, because their CBM is located at the surface with a higher vacuum level and their VBM is distributed on the opposite surface with a lower vacuum level. This work emphasizes the negative role of vacuum level differences of photocatalysts caused by the intrinsic dipole in water splitting.

The role of Astragalus polysaccharides in promoting IEC-6 cell migration from polyamine-mediated Ca2+ regulation.

Astragalus polysaccharide (APS) has a protective effect on injured intestinal mucosa by promoting intestinal cell migration, but the specific mechanism is unclear. The polyamine-mediated calcium signaling pathway is an important mechanism of cell migration, generally, and we tested the hypothesis that APS can protect damaged intestinal mucosa through the polyamine-mediated calcium signaling pathway. High-performance liquid chromatography (HPLC), infrared chromatography, cell scratch test, Western blot, co-immunoprecipitation, polyamine inhibitor (DFMO), si-Cav1, RhoA inhibitor (Rhosin) and Rac1 inhibitor (NSC23766) were used to detect the pharmacodynamic of APS. The results show that APS can promote cell migration. In addition, APS increased the formations of RhoA/TRPC1, Cav1/TRPC1, and Rac1/PLCγ-1 complexes as well as the expressions of TRPC1, PLCγ-1, RhoA, Cav1, and Rac1, and it reversed the inhibitory effect of DFMO on the above factors. APS also reversed the inhibitory effect of si-Cav1 on Cav1 expression, cytoplasmic Ca2+ concentrations ([Ca2+]cyt), and cell migration. Moreover, APS removed the inhibition of NSC23766 and Rhosin on [Ca2+]cyt and cell migration. In vivo study, the water extract of Astragalus membranaceus (WEA) (15 g/kg) reduced the indomethacin-induced injury of intestinal mucosa as well. These observations suggest that APS can treat gastrointestinal mucosal injury through the polyamine calcium signaling pathway.

Meta-analysis of risk factors associated with suicidal ideation after stroke.

BACKGROUND: Over the past decade, increasing attention has been paid on post stroke suicide (PSS), which is one of complications of stroke. The rates of stroke and suicide are relatively high, especially in Asian populations. Thus, a deeper understanding of the prevalence and epidemiological impact of suicide after stroke is urgently needed. Clinical diagnosis and prevention of PSS are at the incipient stage, but the risk factors responsible for the occurrence of PSS in different regions and stages of the disease remain largely unknown. The present meta-analysis aimed to determine the incidence of PSS at different stages and time courses, and to identify the underlying risk factors for PSS. METHODS: We systematically searched the Cochrane library, Embase, PubMed, CNKI and Web of Science databases from their inception until April 2019.The research articles reporting on the risk factor for PSS were screened and included in the meta-analysis. The data from the included studies were extracted according to the predefined criteria. RESULTS: A total of 12 studies (n = 2,693,036) were included for meta-analyses. Of these studies, 7 reporting suicide prevalence were meta-analyzed. The pooled estimate of suicidal ideation rates after stroke was 12%, which could be influenced by multiple risk factors, including sex, smoking, depression, sleep disorders, previous stroke and low household income. Studies conducted in Asia demonstrated higher suicide prevalence (approximately 15%) compared to other regions. Smoking, low family income, depression, heart disease and sleep disorders were important risk factors for PSS. When compared to PSS of more than 1 year, the incidence of suicide within 1 year after stroke was more likely to be statistically significant. It was found that 4 out of every 1000 stroke survivors tended to commit suicide. The results of this meta-analysis showed that depression (OR = 2.32; p < 0.01) was significantly associated with suicidal ideation, regardless of stroke duration. CONCLUSION: PSS is one of the common complications of stroke. Despite some limitations, we successfully identified the risk factors associated with suicidal ideation after stroke. Notably, depression was significantly associated with suicidal ideation, regardless of stroke duration. Targeting this risk factor may be helpful to improve stroke patient care and prevent suicidal ideation after stroke. Future research will be carried out to assess whether suicidal ideation or thoughts and actual suicide attempts are strongly predictive of suicide deaths after stroke (Registration No. CRD42019128813).

Predictive value of gadoxetic acid-enhanced MRI for posthepatectomy liver failure: a systematic review.

OBJECTIVES: Effective and non-invasive biomarkers to predict and avoid posthepatectomy liver failure (PHLF) are urgently needed. This systematic review aims to evaluate the efficacy of gadoxetic acid-enhanced MRI-derived parameters as an imaging biomarker in preoperative prediction of PHLF. METHODS: A systematic literature search was performed in the databases of PubMed/Medline, Web of Science, Embase, and Cochrane Library up to 11 December 2020. Studies evaluating the incidence of PHLF on patients who underwent hepatectomy with preoperative liver function assessment using gadoxetic acid-enhanced MRI were included. Data was extracted using pre-designed tables. The Quality In Prognostic Studies (QUIPS) tool was adopted to evaluate the risk of bias. RESULTS: A total of 15 studies were identified for qualitative synthesis and most studies were marked as low to moderate risk of bias in each domain of QUIPS. The most commonly used parameter was relative liver enhancement or its related parameters. The reported incidence of PHLF ranged from 3.9 to 40%. The predictive sensitivity and specificity of gadoxetic acid-enhanced MRI parameters varied from 75 to 100% and from 54 to 93% in ten reported studies. A majority of the studies revealed that the gadoxetic acid-enhanced MRI parameter was a predictor for PHLF. CONCLUSIONS: Gadoxetic acid-enhanced MRI showed a high predictive capacity for PHLF and represents a promising imaging biomarker in prediction of PHLF. Multicenter, prospective trials with large sample size and reliable, unified liver function parameters are required to validate the efficacy of individual liver function parameters. KEY POINTS: • There is an obvious heterogeneity of the published studies, not only in variance of MRI liver function parameters but also in indication and extent of the liver resection. • Signal intensity (SI)-based parameters derived from gadoxetic acid-enhanced MRI are the commonly used method for PHLF prediction. • Gadoxetic acid-enhanced MRI-derived parameters showed high predictive efficacy for PHLF and can potentially serve as a predictor for the incidence of PHLF.

Study on the pathogenesis of Holmes tremor by multimodal 3D medical imaging: case reports of three patients.

BACKGROUND: We examined for the first time the imaging characteristics of Holmes tremor (HT) through multimodal 3D medical imaging. CASE PRESENTATION: Three patients with Holmes tremor who visited the Affiliated Hospital of Chengdu University of TCM from August 2018 to April 2021 were retrospectively investigated to summarize their clinical and imaging data. RESULTS: Holmes tremor in two of the three patients was caused by hypertensive cerebral hemorrhage and in the third patient induced by hemorrhage due to ruptured brain arteriovenous malformations. HT occurred 1 to 24 months after the primary disease onset and manifested as a tremor in the contralateral limb, mostly in the upper portion. Cranial MRI showed that the lesions involved the thalamus in all three patients. The damaged thalamic nuclei included the ventral anterior nucleus, ventral lateral nucleus and ventromedial lateral nucleus, and the damaged nerve fibers included left thalamocortical tracts in one patient. In the other two patients, the damaged thalamic nuclei included the centromedian and dorsomedial nucleus, and the damaged nerve fibers included left cerebellothalamic and thalamocortical tracts. One patient showed significant improvement after treatment with pramipexole while the other two patients exhibited a poor response, one of whom had no response to the treatment with pramipexole and was only significantly relieved by clonazepam. CONCLUSION: We used multimodal 3D medical imaging for the first time to analyze the pathogenesis of HT and found that multiple thalamic nuclei were damaged. The damaged nuclei and nerve fiber tracts of two patients were different from those of the third patient, with different clinical manifestations and therapeutic effects. Therefore, it is speculated that there may be multiple pathogeneses for HT.

Total ginsenosides promote the IEC-6 cell proliferation via affecting the regulatory mechanism mediated by polyamines.

Epithelial cell proliferation has been demonstrated to be a critical modality for mucosal repair after gastrointestinal mucosal injury. This research aimed to investigate the effect of total ginsenosides upon the proliferation of intestinal epithelial cells (IEC-6), and elucidate its potential mechanisms through polyamine-regulated pathway including the expression of proliferation-related proteins. Total ginsenosides (PGE3) were extracted from Panax ginseng, a Chinese herbal medicine, whose chromatogram was obtained by high performance liquid chromatographic method with evaporative light scattering detection (HPLC-ELSD). The cell proliferation, cell cycle distribution and the level of c-Myc, RhoA, Cdk2 proteins were detected to determine the effects of PGE3 at 25, 50 and100 mg/l doses on IEC-6. Furthermore, rats model of intestinal mucosal injury were induced by the subcutaneous injection of indomethacin, and the effect of Panax ginseng aqueous extracts (PGE1) on intestinal mucosal injury was observed. PGE3 could promote IEC-6 cell proliferation, reduce the proportion of G0/G1 phase cells and elevate the proportion of G2/M + S phase cells, and revert the proliferation and cell cycle arrest induced by DFMO (DL-a-difluoromethylornithine, an inhibitor of polyamines synthesis). PGE3 exposure enhanced the level of c-Myc, RhoA and Cdk2 proteins, and reversed the inhibition of these proteins expression induced by DFMO. The results of gross and pathological scores showed administration of PGE1 significantly alleviated intestinal mucosal injury of rats. Our findings indicate that total ginsenosides promoted the IEC-6 proliferation presumably via its regulation on cell cycle and the expression of proliferation-related proteins regulated by polyamines, and provided a novel perspective for exploring the repair effect of Panax ginseng upon gastrointestinal mucosal injury.

Saikosaponin A improved depression-like behavior and inhibited hippocampal neuronal apoptosis after cerebral ischemia through p-CREB/BDNF pathway.

Post-stroke depression(PSD) is a common complication and associates with poor physical recovery, low quality of life and high mortality after cerebral infarction. However, the pathogenesis of PSD have not been elucidated thoroughly now, and there is a lack of effective therapy in clinic. It reported that Saikosaponin A, one of the main constituents from Chinese herb Bupleurum chinense, has pharmacological activity in anti-depression. Thus, this study aimed to elucidate the potential effects and mechanisms of Saikosaponin A on the depression-like behavior after cerebral ischemic injury in rats. The rat model of PSD was induced by middle cerebral artery occlusion(MCAO) combined with chronic unpredictable mild stress(CUMS) and isolation. Behavior tests including open field test, beam-walking test, sucrose preference and forced swimming tests were performed. Western blot and immunohistochemistry were adopted to evaluate expression of phosphorylated cAMP response element binding protein(p-CREB), brain derived neurotrophic factor(BDNF) and apoptosis-related molecules in the dentate gyrus region of rat hippocampus. The TUNEL assay was used to determine neuronal apoptosis. We found that the rats subjected to MCAO combined with CUMS and isolation experienced significant depressive-like behavior. Administration of Saikosaponin A significantly ameliorated depressive-like behavior, and inhibited neuronal apoptosis, enhanced the level of p-CREB, BDNF and Bcl-2, reduced the level of Bax, Caspase-3 in the hippocampus of PSD rats. These results revealed that Saikosaponin A improved depression-like behavior and inhibited hippocampal neuronal apoptosis after cerebral ischemia, presumably through increasing the expression of BDNF, p-CREB and Bcl-2, as well as decreasing the level of Bax, Caspase-3.

Related risk factors associated with post-stroke fatigue: a systematic review and meta-analysis.

BACKGROUND: Post-stroke fatigue (PSF) is one of the most common complications of stroke and has a negative impact on quality of life over time. Although several therapeutic approaches have been explored in the last decade, the risk factors responsible for the occurrence of PSF are still largely unknown. OBJECTIVE: The aim of this meta-analysis was to identify the risk factors contributing to PSF, especially clinical and social risk factors, which may help to prevent PSF. METHODS: A systematic literature search was performed with PubMed, EMBASE, Cochrane Library, and Web of Science databases from inception until April 2019. Only original studies measuring the association between potential risk factors and PSF were included. All relevant data the included studies were extracted by two independent reviewers using predefined data fields. RESULTS: Fourteen studies (n = 3933) were included in this meta-analysis. Female (OR = 1.39; p < 0.01), thalamus (OR = 1.76; p = 0.02), leucoaraiosis (OR = 1.73; p < 0.01), NIHSS score (OR = 1.16; p < 0.01), modified Rankin Scale (OR = 1.63; p < 0.01), depression (OR = 1.75; p < 0.01), and sleeping disturbances (OR = 2.01; p < 0.01) were all significantly associated with PSF. In the subgroup analysis, depression (OR = 2.75; p < 0.01) tended to be associated with Asian patients with PSF. For patients who had a stroke survive for more than half a year, PSF was more likely to occur in stroke survivors with depression (OR = 1.46; p < 0.01), anxiety (OR = 1.13; p < 0.01), or sleeping disturbances (OR = 1.98; p < 0.01). CONCLUSION: Despite some limitations, this study first identified that female and depression conferred an increased susceptibility to PSF, regardless of whether in European or Asian populations. Risk factors associated with PSF included female, thalamic, leucoaraiosis, depression, sleeping disturbances, diabetes mellitus, and anxiety. This meta-analysis shows that chronic PSF appears to be largely attributable to patients with multiple comorbidities. It is necessary to strengthen the treatment for stroke-related complications and improve stroke patient care, which could help to reduce the incidence of PSF. TRIAL REGISTRATION: CRD42019128751.

Most permissive liveness-enforcing Petri net supervisors for discrete event systems via linear monitors.

This paper proposes a deadlock prevention method to design a maximally permissive liveness-enforcing pure Petri net supervisor for a discrete event system, if such a supervisor exists; otherwise, it obtains the most permissive one in the sense that no other pure liveness-enforcing supervisors via linear monitors can be more permissive than it. This paper exploits an iterative method. At each iteration, a first-met bad marking (FBM) is singled out and an integer linear programming problem (ILPP) is configured. If a feasible solution can be found for the ILPP, then a place invariant (PI) is designed to prohibit the FBM from being reached while no legal marking is forbidden. If the ILPP has no solution, we collect all these FBMs that cannot be optimally controlled. For each of such FBMs, another ILPP is designed to find the least number of legal markings whose reachability conditions contradict the current considered FBM and enumerate all the optimal solutions of this ILPP. Based on it, we develop a 0-1 linear programming problem to find the maximal number of legal markings after removing all the contradictory legal markings. Then, the new sets of legal markings and FBMs are obtained, and we return to the iteration stage to redesign a PI to control each FBM if the ILPP has a feasible solution. Repeat the above process until no FBM can be reached. Finally, a most permissive pure liveness-enforcing supervisor via linear monitors is derived. Two Petri net models are used to illustrate the proposed method.

Antidepressant-like effects of paeoniflorin on post-stroke depression in a rat model.

BACKGROUND: Post-stroke depression (PSD) is one of the most prevalent emotional disorders after stroke and often results in poor outcomes. However, the underlying physiopathologic mechanism and effective treatment of PSD remain poorly elucidated. OBJECTIVE: To investigate whether paeoniflorin has antidepressant-like activity in a rat model of PSD. METHODS: Rats were randomly divided into four groups: sham-operated control (Sham), PSD, paeoniflorin (with PSD) and fluoxetine group(with PSD). PSD was developed by the right middle cerebral artery occlusion followed 21 days chronic unpredictable mild stress combined (CUMS) with raised alone. Tests of sucrose preference and open field were used to assess the depression-like behavior. Neurological function was evaluated by neurological deficit score and beam balance test. Expression of phosphorylated CREB (p-CREB) and brain-derived neurotrophic factor (BDNF) in the CA1 region of the hippocampal complex was evaluated by western blot and immunofluorescence. RESULTS: Te depressive-like behaviors markedly improved after paeoniflorin and fluoxetine treatment. Furthermore, paeoniflorin treatment significantly increased BDNF and p-CREB expression in the CA1 region. CONCLUSIONS: Observed results suggested that paeoniflorin could ameliorate the symptoms and improve the functional capability of PSD rats, similar to the effect of fluoxetine. ABBREVIATIONS: PSD: post-stroke depression; CUMS: chronic unpredictable mild stress stimulation; MCAO: middle cerebral artery occlusion; OFT: open field test; SPT: sucrose preference test, NDS: neurological deficit score, BBT: beam balance test; BDNF: brain-derived neurotrophic factor protein; p-CREB: phosphorylated Cyclic-AMP responsive element binding protein.