Cyp3A4 *1G polymorphism is associated with alcohol drinking: A 5-year retrospective single centered population-based study in China.

INTRODUCTION: We investigated the epidemiology of Cytochrome P450 (CYP) 3A4 genotype and the relationship between CYP3A4 genotype and alcohol drinking habits. MATERIALS AND METHODS: A single-centered retrospective study was conducted on 630 patients who underwent CYP3A4*1G genetic testing. Their relevant information on epidemiology and etiology was collected. Laboratory testing, including CYP3A4*1G genotype, liver function tests, and serum lipid measurements were performed. Bi-variate logistic regressions were used to examine the relationship between variables. The relationship between alcohol drinking and CYP3A4*1G genotype was estimated. Demographic and clinical features were analyzed. Participants with drinking history were divided into non-heavy drinking and heavy drinking groups. Liver function and dyslipidemia of participants with drinking histories were compared between CYP3A4*1G mutation (GA+AA) and wild-type (GG) groups. RESULTS: Participants with CYP3A4*1G mutation(GA+AA) had an increased adjusted odds ratio (AOR) of 2.56 (95% CI, 1.4-4.65; P = 0.00) for alcohol abuse when compared with participants without CYP3A4 mutation (GG). In the subgroup of participants with alcohol abuse, there are no significant differences in liver injury levels and serum lipid levels between CYP3A4*1G mutant and wild-type groups. Patients with CYP3A4*1G mutation had an increased AOR of cardiac-vascular diseases and malignant diseases compared with patients without CYP3A4*1G mutation. The epidemiology had no difference between GA and AA group. CONCLUSION: The study indicated that there was association between alcohol drinking and CYP3A4*1G genetic mutation. In the subgroup of participants with alcohol abuse, there are no significant differences in liver injury and dyslipidemia between CYP3A4*1G mutant and wild-type groups. CYP3A4*1G mutation was also related to cardiac-vascular diseases and malignant diseases.

Increased age, bilirubin, international normalized ratio, and creatinine score to triglyceride ratio are associated with alcohol-associated primary liver carcinoma: a single-centered retrospective study.

BACKGROUND: This study analyzed the clinical features and biomarkers of alcohol-associated liver disease (ALD) to investigate the diagnostic value of age, bilirubin, international normalized ratio (INR), and creatinine (ABIC) score to triglyceride (TG) ratio (ABIC/TG) in ALD-associated primary liver carcinoma (PLC). MATERIALS AND METHODS: Data were collected from 410 participants with ALD, and the epidemiological and clinical records of 266 participants were analyzed. Participants were divided into ALD-without-PLC and ALD-associated-PLC groups. Relationships between clinical characteristics, biomarkers and ALD-associated PLC were estimated. Serum lipid levels and liver function were compared between ALD patients without PLC and patients with ALD-associated PLC. Scoring systems were calculated to investigate ALD severity. The robustness of the relationship was analyzed by the receiver operating characteristic (ROC) curve. RESULTS: Age and dyslipidemia were more strongly associated with ALD-associated PLC than with ALD-without PLC, with AORs of 2.39 and 0.25, respectively, with P less than 0.05. Drinking time and average daily intake, ABIC score, and ABIC/TG ratio were significantly higher in the ALD-associated-PLC group than in the ALD-without-PLC group. The AUC for the ABIC/TG ratio predicting the incidence of PLC was 0.80 (P < 0.01), which was higher than that of the ABIC and TG scores alone; additionally, the specificity and Youden index for the ABIC/TG ratio were also higher, and the cutoff value was 6.99. CONCLUSIONS: In ALD patients, age, drinking time, and average daily intake were risk factors for PLC. Drinking time, average daily intake, TG and ABIC score have diagnostic value for ALD-associated PLC. The ABIC/TG ratio had a higher AUC value and Youden index than the ABIC score and TG level.

Increased TG to HDL-C ratio is associated with severity of drug-induced liver injury.

We investigated the relationship between dyslipidemia and drug-induced liver injury (DILI), especially the level of triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) in severe DILI. In this single-centered retrospective study, of 326 patients with DILI, 221 patients were analyzed. Control groups include medication using group and acute hepatitis B group. The relationship between dyslipidemia and DILI was estimated. Demographic and clinical features were analyzed. Dyslipidemia and TG/HDL-C ratios were compared between DILI and control groups, DILI mild group and severe group. The area under the receiver-operating characteristic curve (AUC) was used to evaluate the credibility of the relationship and to find cut-off points. Dyslipidemia is related to DILI when compared with medication using control group (AOR 4.60; 95% CI 2.81-7.54; P < 0.01) and compared with acute hepatitis B group (AOR 2.12; 95% CI 1.37-3.29; P < 0.01). Dyslipidemia is associated with the severity of DILI (AOR 25.78; 95% CI 7.63-87.1; P < 0.01). TG/HDL-C ratio is higher in DILI group than that of medication using control group, also higher in severe DILI group than that of mild DILI group. AUCs for TG/HDL-C ratio to indicate the severity of DILI was 0.89 (P < 0.05), the cut-off point was 2.35. Dyslipidemia and TG/HDL-C ratio were related to DILI occurrence. Severe liver injury in DILI was associated with dyslipidemia and elevated TG/HDL-C ratio.

Triglyceride to HDL-C ratio is associated with plasma D-dimer levels in different types of pancreatitis.

This study aims to evaluate levels of D-dimer and serum lipid in different types of pancreatitis, and the relationship between D-dimer and dyslipidemia, especially triglyceride to HDL-C ratio (TG/HDL-C) in different types of pancreatitis. We analyzed the D-dimer and dyslipidemia levels in acute pancreatitis (AP), recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP). A single-centered retrospective study was conducted on 1013 patients diagnosed with AP, RAP or CP. Only patients hospitalized within 24 h of onset were included, and 204 patients were enrolled in pancreatitis groups. 68 normal persons without pancreatitis, malignant diseases, pregnancy, or organ failure, who had health check-ups, were enrolled in the control group. Blood samples were taken within 24 h of admission. The relevant information on epidemiology and etiology was collected. D-dimer and serum lipid levels in different types of pancreatitis were analyzed. Furthermore, the area under the receiver-operating characteristic curve (AUC) was used to estimate the validity of the predictor and to define optimal cut-off points for prediction. We found that D-dimer and TG/HDL-C ratio could distinguish mild AP (MAP) and non-MAP in AP and RAP patients. The D-dimer level was related to TG/HDL-C ratio and severity of pancreatitis, with the coefficient correlation of 0.379 and 0.427(p < 0.05), respectively. TG/HDL-C was related to D-dimer in different types of pancreatitis. Logistic regression analysis was conducted in the parameters at admission like alcohol abuse, dyslipidemia and coagulation disturbance in distinguishing AP and RAP groups from the control group, and the parameter like diabetes in RAP and CP groups significantly increased compared with that of the control group. The value of D-dimer level and TG/HDL-C ratio in predicting the severity of AP and RAP was confirmed but there was no significant difference between CP group and the control group. The D-dimer level was related to dyslipidemia and TG/HDL-C ratio.

Expressional and functional characteristics of checkpoint kinase 1 as a prognostic biomarker in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is the most common pathological subtype of liver cancer and is the third leading cause of cancer death worldwide. Checkpoint kinase 1 (CHEK1), an essential serine/threonine kinase that regulates the cell cycle, is reported to be associated with carcinogenesis. However, the biological role and clinical significance of CHEK1 in HCC are still incompletely known. Methods: In this research, CHEK1 messenger RNA (mRNA) levels in various liver hepatocellular carcinoma (LIHC) cohorts from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were evaluated. The Kaplan-Meier database was applied to identify the correlation between survival time and CHEK1 expression in patients with HCC. Gene set enrichment analysis (GSEA) was performed to explore the potential mechanism of CHEK1 in HCC, and NetworkAnalyst v. 3.0 (https://www.networkanalyst.ca/) was used to construct the regulatory networks of CHEK1 in HCC. Discriminant Regulon Expression Analysis (DoRothEA) was used to detect the activity of transcriptional factors (TFs) in gene-enriched cells (EC) with CHEK1 coexpression. In vitro experiments were conducted to investigate the effects of CHEK1 on the biological function of HCC cells. Results: The CHEK1 mRNA level was overexpressed in HCC, and increased CHEK1 expression correlated with poor survival outcomes. The homo sapiens-microRNA-195 (hsa-miR-195) may have contributed to the upregulation of CHEK1 in HCC. GSEA and NetworkAnalyst v. 3.0 showed that CHEK1 played a crucial part in tumor proliferation of HCC and may be regulated by TF E2F1. DoRothEA showed increased transcriptional activity of E2F1 in gene-EC with CHEK1 coexpression. Moreover, experiments of cell function showed that the knockdown of CHEK1 weakened the aggressive behavior and proliferation of HCC cells. Overexpression of E2F1 increased the proliferation and invasion of HCC cells in vitro, while the silencing of CHEK1 dampened cell invasion induced by E2F1 overexpression. Conclusions: These results identified the prognostic significance and expression characteristics of CHEK1 in HCC through bioinformatics analysis and experimental verification. This lays the foundation for further research on the diagnosis and treatment of HCC.

H2AFZ Is a Prognostic Biomarker Correlated to TP53 Mutation and Immune Infiltration in Hepatocellular Carcinoma.

H2A family member Z (H2AFZ) is a highly conserved gene encoding H2A.Z.1, an isoform of histone variant H2A.Z, and is implicated in cancer. In this study, we report that overexpression of H2AFZ is associated with tumor malignancy and poor prognosis in HCC patients. Functional network analysis suggested that H2AFZ mainly regulates cell cycle signaling and DNA replication via pathways involving several cancer-related kinases and transcription factor E2F1. Further studies revealed that H2AFZ overexpression is regulated by TP53 mutation and led to an attenuation of rapid proliferation phenotype and aggressive behavior in HCC cells. Moreover, we found that H2AFZ was related to immune infiltrations and was co-expressed with immune checkpoint genes, including CD274 (PD-L1), CTLA-4, HAVCR2 (TIM3), LAG3, PDCD1 (PD-1), and TIGIT (VSIG9) in HCC, indicating that H2AFZ-overexpressed HCC patients may be sensitive to immune checkpoint blockades (ICBs). Integrated analysis suggested that H2AFZhigh/TP53mut patients had the shortest OS and PFS time, but most likely to respond to ICBs. These findings indicate that the H2AFZ possesses potential value as a novel prognostic indicator for HCC patients and is correlated with immune infiltration in HCC, laying a foundation for future study of HCC investigation and intervention.

Altered static and dynamic voxel-mirrored homotopic connectivity in subacute stroke patients: a resting-state fMRI study.

Sixty-four subacute stroke patients and 55 age-matched healthy controls (HCs) underwent a resting-state functional magnetic resonance imaging scan using an echo-planar imaging sequence and high-resolution sagittal T1-weighted images using a three-dimensional magnetization-prepared rapid gradient echo sequence. Static and dynamic voxel-mirrored homotopic connectivity (VMHC) was computed, respectively. The relationships between the clinical measures, including National Institutes of Health Stroke Scale (NIHSS), illness duration, Fugl-Meyer assessment for upper and lower extremities (FMA-total) and size of lesion volume, and the static/ dynamic VMHC variability alterations in stroke patients were calculated. The stroke patients showed significantly increased static VMHC in the corpus callosum, middle occipital gyrus and inferior parietal gyrus, and decreased static VMHC in the inferior temporal gyrus and precentral gyrus (PreCG) compared with those of HCs. For dynamic VMHC variability, increased dynamic VMHC variability in the inferior temporal gyrus and PreCG was detected in stroke patients relative to that in HCs. Correlation analysis exhibited that significant negative correlations were shown between the FMA scores and dynamic VMHC variability in PreCG. The present study suggests that combined static and dynamic VMHC could be helpful to evaluate the motor function of stroke patients and understand the intrinsic differences of inter-hemispheric coordination after stroke.

Effects of home-based telerehabilitation in patients with stroke: A randomized controlled trial.

OBJECTIVE: To determine the effects of a 12-week home-based motor training telerehabilitation program in patients with subcortical stroke by combining motor function assessments and multimodality MRI analysis methods. METHODS: Fifty-two patients with stroke and hemiplegia were randomly assigned to either a home-based motor training telerehabilitation (TR) group or a conventional rehabilitation (CR) group for 12 weeks. The Fugl-Meyer assessment (FMA) for upper and lower extremities and the modified Barthel Index were used as primary outcomes. The secondary outcomes included resting-state functional connectivity (rsFC) between the bilateral M1 areas, gray matter volumes of the primary motor cortex (M1) areas, and white matter integrity of the corticospinal tract. Analysis of covariance was applied to examine the effects of the home-based motor training TR program on neural function recovery and brain plasticity. RESULTS: Compared with the CR group, the TR group showed significant improvement in the FMA (p = 0.011) and significantly increased M1-M1 rsFC (p = 0.031) at the end of the rehabilitation. The M1-M1 rsFC change was significantly positively correlated with the FMA change in the TR group (p = 0.018). CONCLUSION: This study showed a beneficial effect of the home-based motor training telerehabilitation program on motor function in patients with stroke, which was accompanied by enhanced interhemispheric functional connectivity of the M1 areas. We inferred that it is feasible, safe, and efficacious for patients with stroke to receive professional rehabilitation training at home. The combined use of imaging biomarkers should be encouraged in motor training clinical studies in patients with stroke. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with stroke with hemiplegia, home-based telerehabilitation compared to conventional rehabilitation significantly improves some motor function tests.

CD86+/CD206+ tumor-associated macrophages predict prognosis of patients with intrahepatic cholangiocarcinoma.

BACKGROUND: As the main cellular ingredients of tumor microenvironment, tumor-associated macrophages (TAMs) play a vital role in tumor development and progression. Recent studies have suggested that TAMs are sensitive and specific prognostic factors in numerous cancers. The primary purpose of this study is to determine the prognostic significance of TAMs in intrahepatic cholangiocarcinoma (ICC). METHODS: Immunohistochemical staining of CD68, CD86 and CD206 were performed in tissue microarrays containing 322 patients, who underwent surgical resection and were pathologically diagnosed with ICC. The prognostic value of CD68, CD86 and CD206 were evaluated by Kaplan-Meier analysis (log-rank test) and nomogram models. RESULTS: We demonstrated that the CD86+/CD206+ TAMs model was an independent prognostic index for ICC patients. Patients with low CD86+ TAMs and high CD206+ TAMs infiltration had a markedly worse prognosis and increased risk of post-operative recurrence when compared to high CD86+ TAMs and low CD206+ TAMs intratumoral infiltration. Furthermore, subgroup analysis indicated that the CD86+/CD206+ TAMs model predicted prognosis of ICC patients more powerfully than single macrophage immunomarker. Interestingly, the CD86+/CD206+ TAMs model could further distinguish prognosis of CA-199 negative ICC patients, who were generally presumed to have a more favorable outcome. In order to further perfect the prognostic value of the CD86+/CD206+ TAMs model, we constructed and validated a postoperative nomogram to predict overall survival and recurrence-free survival time in ICC patients. CONCLUSIONS: These findings indicate that the CD86+/CD206+ TAMs model possess potential value as a novel prognostic indicator for ICC patients.

M2-polarized tumor-associated macrophages promote epithelial-mesenchymal transition via activation of the AKT3/PRAS40 signaling pathway in intrahepatic cholangiocarcinoma.

Tumor-associated macrophages (TAMs) have been considered as a major component of the tumor microenvironment. However, the crosstalk between M2-polarized tumor-associated macrophages (M2-TAMs) and intrahepatic cholangiocarcinoma (ICC) remains undetermined. In the present study, we aimed to clarify the role of M2-TAMs in ICC and the underlying mechanism. The in vitro assay demonstrated M2-TAMs promoted epithelial-mesenchymal transition (EMT) of ICC cells, resulting in enhanced cell invasion and metastasis ability. Moreover, M2-TAMs modulated the microenvironment of ICC by increasing the secretion of cytokines (GM-CSF, tumor necrosis factor-α [TNF-α], ICAM-1, interleukin-6 [IL-6], etc) and chemokines (CCL1, CCL3, etc). In addition, p-AKT (Ser473) and p-PRAS40 (Thr246) were upregulated in ICC cells when cocultured with M2-TAMs or treated with M2-TAMs secreted core cytokines (GM-CSF, TNF-α, ICAM-1, and IL-6). Consistently, AKT3 silencing (but not AKT1 silencing and AKT2 silencing) markedly inhibited phosphorylation of AKT and PRAS40 of ICC cells and inhibited the EMT process when cocultured with M2-TAMs. Taken together, the current data indicated that M2-TAMs promoted ICC cells EMT, partially through increasing secretion of cytokines and chemokines, thus modulating the microenvironment and activating the AKT3/PRAS40 signaling pathway.

Exosomes isolated from CAPS1­overexpressing colorectal cancer cells promote cell migration.

Calcium­dependent activator protein for secretion 1 (CAPS1) has been reported to promote metastasis in colorectal cancer (CRC), however, the underlying mechanisms have not yet been elucidated. The present study revealed that exosomes derived from CAPS1­overexpressing CRC cells could enhance the migration of normal colonic epithelial FHC cells. GW4869, an inhibitor of exosomes, could attenuate the migration of FHC cells. Furthermore, liquid chromatography­mass spectrometry (LC­MS) and bioinformatics analysis demonstrated that overexpression of CAPS1 could alter the expression pattern of exosomal proteins involved in cell migration. Bone morphogenetic protein 4, which may serve vital roles in the process of CAPS1­induced cell migration, was downregulated in the exosomes. In summary, the present results demonstrated that CAPS1 promotes cell migration by regulating exosomes. Inhibiting the secretion of exosomes may be helpful for the treatment of patients with metastatic CRC.

Oncogenic role of phospholipase C-γ1 in progression of hepatocellular carcinoma.

AIM: Phospholipase C-γ1 (PLCG1) was previously found to be involved in a variety of oncogenic behaviors such as cell motility, cell proliferation, cell migration, and invasion. However, its function in hepatocellular carcinoma (HCC) was unknown. Here, we explored the expression pattern and function of PLCG1 in HCC progression. METHODS: Expression of PLCG1 was examined by western blotting in hepatoma cells and human tumor tissues. Expression was also detected by immunohistochemistry in 150 HCC clinical samples, and its clinical significance was analyzed. The influence of PLCG1 on HCC carcinogenesis were determined in vitro and in vivo. The underlying mechanisms were explored by detecting the expression of critical molecules of signaling pathways. RESULTS: The results showed that PLCG1 was overexpressed in hepatoma cell lines and clinical HCC tissues. Increased PLCG1 expression in tumor tissues was remarkably correlated with poor clinical features of HCC. Patients with positive PLCG1 expression in tumor tissues had shorter overall survival and relapse-free survival. Phospholipase C gamma 1 could substantially promote cell proliferation, anchor growth, and cell invasion in vitro. The in vivo study showed that inhibition of PLCG1 in hepatoma cells significantly repressed tumor growth in nude mice. Furthermore, we showed that PLCG1 might exert its function by activating the mitogen-activated protein kinase and nuclear factor-κB signaling pathways. CONCLUSION: Our data indicated that PLCG1 could act as an oncogene in HCC carcinogenesis and could serve as a valuable prognostic marker and potential therapeutic target for HCC.

Alterations of static functional connectivity and dynamic functional connectivity in motor execution regions after stroke.

The aims of this study were to examine both static functional connectivity (FC) and dynamic FC alterations in motor execution regions after stroke and to investigate whether the altered static or dynamic FC was associated with the clinical behaviors in stroke patients. Seventy-six stroke patients and 55 healthy controls (HC) were recruited. Static FC and dynamic FC maps were computed based on the seeds of six core regions in motor execution network. Correlation analyses were performed between static or dynamic FC and clinical behavioral scores in stroke patients. Compared with the HC, the stroke patients had significantly higher static FC between the seeds and the precentral or postcentral gyrus, frontal gyrus, inferior parietal lobule, thalamus and insula, and lower static FC between the seeds and the cerebellum and middle temporal gyrus. There were significant differences in dynamic FC between the seeds and precuneus, calcarine gyrus, insula, inferior parietal lobule, precentral gyrus, and middle temporal, frontal or occipital gyrus between the stroke patients and HC. Furthermore, a significant negative correlation was found between the Fugl-Meyer assessment scores and dynamic FC of the ipsilesional primary motor cortex and contralesional precentral gyrus in patients. The current study shows that the patterns of both static FC and dynamic FC changed after stroke, and correlation between motor function and temporal variability in the FC of the precentral gyrus was significant in stroke patients. Our findings indicate that dynamic FC might be a potential indicator for evaluating motor function after stroke.

Spermine oxidase is upregulated and promotes tumor growth in hepatocellular carcinoma.

AIM: The polyamine catabolic enzyme, spermine oxidase (SMOX) is upregulated in chronic inflammatory conditions and linked to increased reactive oxygen species and DNA damage in various forms of cancers. The present study aims to explore the expression pattern and biological function of SMOX in hepatocellular carcinoma (HCC). METHODS: We used quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry to examine SMOX expression in four HCC cell lines and 120 HCC clinical samples, and the clinical significance of SMOX was analyzed. The biological function of SMOX on HCC cells was detected both in vitro and in vivo. RESULTS: Results showed that SMOX was overexpressed in HCC cell lines and clinical HCC tissues. Moreover, SMOX expression levels were gradually increased in normal liver, chronic hepatitis, and HCC tissues. Increased SMOX expression was correlated with poor clinical features of HCC. Patients with positive SMOX expression in tumor tissues indicated worse overall survival (P = 0.008) and shorter relapse-free survival (P = 0.002). Knockdown of SMOX inhibited HCC cell proliferation, arrested cell cycle at S phase, and resulted in an increase of apoptosis. The in vivo study showed that inhibition of SMOX in HCC cells significantly repressed tumor growth in nude mice. Furthermore, we showed that SMOX might exert its function by regulating the phosphatidylinositol 3'-kinase/protein kinase B signaling pathway. CONCLUSION: Our data indicated that SMOX upregulation could be a critical oncogene in HCC and might serve as a valuable prognostic marker and potential therapeutic target for HCC.

Defibrinogen Therapy for Acute Ischemic Stroke: 1332 Consecutive Cases.

This study aimed to examine the effectiveness of defibrinogen therapy on functional recovery and safety among 1332 consecutive ischemic stroke patients who had not received intravenous thrombolysis with recombinant tissue plasminogen activator. Stroke patients undergoing conservative and relatively individualized multiple-day dosing regimens of defibrinogen therapy between January 1, 2008 and May 30, 2016 were enrolled. Data were analyzed according to functional success (Barthel Index of 95 or 100, mRS of 0 or 1) and safety variables (intracranial hemorrhage, mortality and stroke recurrence). At 12 months, 18.62% (203/1087) of patients were lost to follow-up. The functional success rates were 39.84% (526/1320) and 42.23% (459/1087) as assessed by BI at 3 months and 12 months, respectively. Fifteen patients had asymptomatic intracranial hemorrhage within 24 hours after the initial defibrase administration. During the 14 days after hospitalization, 12 patients were diagnosed with symptomatic intracranial hemorrhage (sICH) and a total of 12 patients died from all causes. At 3 months, 56 patients were dead and 21 patients had recurrent stroke. The percentage of death and recurrence of stroke at 12 months were 6.81% and 3.22%, respectively. Results from the historical control showed no significant differences of functional success were detected between the patients treated with rt-PA within 6 hours of stroke onset in NINDS II and the patients treated with defibrase within 6 hours after stroke in the present study. The multiple-day dosing regimen of defibrinogen therapy using defibrase applied in the present study could achieve functional improvement among acute ischemic stroke patients, with low risks of mortality when compared with other similar studies. However, the efficacy and safety of such a defibrinogenating therapy is needed to be verified by RCTs with large sample size.

Establishment of a 12-gene expression signature to predict colon cancer prognosis.

A robust and accurate gene expression signature is essential to assist oncologists to determine which subset of patients at similar Tumor-Lymph Node-Metastasis (TNM) stage has high recurrence risk and could benefit from adjuvant therapies. Here we applied a two-step supervised machine-learning method and established a 12-gene expression signature to precisely predict colon adenocarcinoma (COAD) prognosis by using COAD RNA-seq transcriptome data from The Cancer Genome Atlas (TCGA). The predictive performance of the 12-gene signature was validated with two independent gene expression microarray datasets: GSE39582 includes 566 COAD cases for the development of six molecular subtypes with distinct clinical, molecular and survival characteristics; GSE17538 is a dataset containing 232 colon cancer patients for the generation of a metastasis gene expression profile to predict recurrence and death in COAD patients. The signature could effectively separate the poor prognosis patients from good prognosis group (disease specific survival (DSS): Kaplan Meier (KM) Log Rank p = 0.0034; overall survival (OS): KM Log Rank p = 0.0336) in GSE17538. For patients with proficient mismatch repair system (pMMR) in GSE39582, the signature could also effectively distinguish high risk group from low risk group (OS: KM Log Rank p = 0.005; Relapse free survival (RFS): KM Log Rank p = 0.022). Interestingly, advanced stage patients were significantly enriched in high 12-gene score group (Fisher's exact test p = 0.0003). After stage stratification, the signature could still distinguish poor prognosis patients in GSE17538 from good prognosis within stage II (Log Rank p = 0.01) and stage II & III (Log Rank p = 0.017) in the outcome of DFS. Within stage III or II/III pMMR patients treated with Adjuvant Chemotherapies (ACT) and patients with higher 12-gene score showed poorer prognosis (III, OS: KM Log Rank p = 0.046; III & II, OS: KM Log Rank p = 0.041). Among stage II/III pMMR patients with lower 12-gene scores in GSE39582, the subgroup receiving ACT showed significantly longer OS time compared with those who received no ACT (Log Rank p = 0.021), while there is no obvious difference between counterparts among patients with higher 12-gene scores (Log Rank p = 0.12). Besides COAD, our 12-gene signature is multifunctional in several other cancer types including kidney cancer, lung cancer, uveal and skin melanoma, brain cancer, and pancreatic cancer. Functional classification showed that seven of the twelve genes are involved in immune system function and regulation, so our 12-gene signature could potentially be used to guide decisions about adjuvant therapy for patients with stage II/III and pMMR COAD.

Effectiveness and neural mechanisms of home-based telerehabilitation in patients with stroke based on fMRI and DTI: A study protocol for a randomized controlled trial.

BACKGROUND: Stroke is one of leading diseases causing adult death and disability worldwide. Home-based telerehabilitation has become a novel approach for stroke patients as effective as conventional rehabilitation, and more convenient and economical than conventional rehabilitation. However, there is no study assessing the mechanism of home-based telerehabilitation in promoting motor recovery among stroke patients with hemiplegic. AIMS: This study is designed to determine the efficacy and explore the mechanism of motor recovery after home-based telerehabilitation in stroke patients with motor deficits. METHODS/DESIGN: In a single-blinded randomized controlled pilot study, patients with acute subcortical stroke (n = 40) are assigned to receive home-based telerehabilitation or conventional rehabilitation. Task-based or resting-state functional magnetic resonance imaging (rs-fMRI), diffusion tensor imaging (DTI), and Fugl-Meyer assessment (FMA) score will acquired before and after rehabilitation. Activation volume of bilateral primary motor (M1), supplementary motor area (SMA), premotor cortex (PMC); lateralization index (LI) of interhemispheric M1, SMA, and PMC; functional connectivity of bilateral M1, SMA, PMC; fractional anisotropy (FA) will be measured; correlation analyses will be performed between neuroimaging biomarkers and FMA score pre- and postrehabilitation. DISCUSSION: We present a study design and rationale to explore the effectiveness and neural mechanism of home-based rehabilitation for stroke patients with motor deficits. The study limitations related to the small-amount sample. Moreover, home-based rehabilitation may provide an alternative means of recovery for stroke patients. Ultimately, results of this trial will help to understand the neural mechanism of home-based telerehabilitation among stroke patients with hand movement disorder.