Scalp acupuncture for post-stroke spastic hemiparesis: A systematic review and meta-analysis.

BACKGROUND: Spastic paralysis is one of the most common sequelae of stroke, severely affecting patients' limb function and reducing their quality of life. Scalp acupuncture (SA) has been shown to significantly improve cerebral blood supply and reduce the severity of limb spasticity. This meta-analysis aims to systematically evaluate the clinical efficacy of SA in the treatment of post-stroke spastic paralysis, providing evidence-based medicine for clinical management of this condition. METHODS: We comprehensively searched databases including China National Knowledge Infrastructure, Wanfang Data, VIP Chinese Science and Technology Periodical Database, China Biomedical Literature Database, PubMed, Embase, and Cochrane Library. Randomized controlled trials investigating the efficacy of SA in post-stroke spastic paralysis were identified until July 28, 2023. Meta-analysis was conducted using RevMan 5.4 and Stata17.0. RESULTS: A total of 16 studies were included. Meta-analysis showed that the modified Ashworth spasticity assessment scale in the SA group was significantly higher than that in the rehabilitation group (mean difference [MD] = -0.56, 95% confidence interval [CI] [-0.75, -0.37], Z = 5.67, P < .00001). The simplified Fugl-Meyer motor function assessment scale in the SA group was significantly higher than that in the rehabilitation group (MD = 5.86, 95% CI [3.26, 8.46], Z = 4.41, P < .0001). The modified Barthel index assessment scale in the SA group was significantly higher than that in the rehabilitation group (MD = 5.79, 95% CI [4.73, 6.84], Z = 10.77, P < .00001). Additionally, the clinical effective rate in the SA group was significantly higher than that in the rehabilitation group (relative risk = 1.25, 95% CI [1.16, 1.36], Z = 5.42, P < .00001). CONCLUSION: SA combined with rehabilitation therapy has certain advantages in reducing limb spasticity, improving limb function, and enhancing activities of daily living in patients with post-stroke spastic paralysis. This study provides reference and theoretical support for the promotion of SA in the treatment of this condition.

Astrocytes in intracerebral hemorrhage: impact and therapeutic objectives.

Intracerebral hemorrhage (ICH) manifests precipitously and profoundly impairs the neurological function in patients who are affected. The etiology of subsequent injury post-ICH is multifaceted, characterized by the intricate interplay of various factors, rendering therapeutic interventions challenging. Astrocytes, a distinct class of glial cells, interact with neurons and microglia, and are implicated in a series of pathophysiological alterations following ICH. A comprehensive examination of the functions and mechanisms associated with astrocytic proteins may shed light on the role of astrocytes in ICH pathology and proffer innovative therapeutic avenues for ICH management.

A pancancer analysis of the clinical and genomic characteristics of multiple primary cancers.

Multiple primary cancer (MPC) denotes individuals with two or more malignant tumors occurring simultaneously or successively. Herein, a total of 11,000 pancancer patients in TCGA database (1993-2013) were divided into MPC or non-MPC groups based on their history of other malignant tumors. The incidence of MPC has risen to 8.5-13.1% since 2000. Elderly individuals, males, early-stage cancer patients, and African Americans and Caucasians are identified as independent risk factors (p < 0.0001). Non-MPC patients exhibit significantly longer overall survival (OS) and disease-free survival (DFS) (p = 0.0038 and p = 0.0014). Age (p < 0.001) and tumor staging at initial diagnosis (p < 0.001) contribute to this difference. In our center, MPC was identified in 380 out of 801 tumor events based on SEER criteria. The peak occurrence of secondary primary was about 1-5 years after the first primary tumor, with a second small peak around 10-15 years. Multiple tumors commonly occur in the same organ (e.g., breast and lung), constituting 12.6%. Certain cancer types, notably skin cutaneous melanoma (SKCM), exhibit significantly higher tumor mutational burden (TMB) in the MPC group (17.31 vs. 6.55 mutations/MB, p < 0.001), with high TMB associated with improved survival (p < 0.001). High TMB in MPC may serve as a predictor for potential immunotherapy application.

The Crosstalk Between Immune Cells After Intracerebral Hemorrhage.

The inflammatory mechanism of intracerebral hemorrhage (ICH) has been widely studied, and it is believed that the regulation of this mechanism is of great significance to the prognosis. In the early stage of the acute phase of ICH, the release of a large number of inflammatory factors around the hematoma can recruit more inflammatory cells to infiltrate the area, further release inflammatory factors, cause an inflammatory cascade reaction, aggravate the volume of cerebral hematoma and edema and further destroy the blood-brain barrier (BBB), according to this, the crosstalk between cells may be of great significance in secondary brain injury (SBI). Because most of the cells recruited are inflammatory immune cells, this paper mainly discusses the cells based on the inflammatory mechanism to discuss their functions after ICH, we found that among the main cells inherent in the brain, glial cells account for the majority, of which microglia are the most widely studied and it can interact with a variety of cells, which is reflected in the literature researches on its pathogenesis and treatment. We believe that exploring multi-mechanism and multi-cell regulated drugs may be the future development trend, and the existing research, the comparison and unification of modeling methods, and the observation of long-term efficacy may be the first problem that researchers need to solve.

An Overview of the Mechanisms Involved in Neuralgia.

Neuralgia is a frequently occurring condition that causes chronic pain and burdens both patients and their families. Earlier research indicated that anti-inflammatory treatment, which was primarily utilized to address conditions like neuralgia, resulted in positive outcomes. However, recent years have witnessed the emergence of various novel mechanisms associated with pain-related disorders. This review provides a concise overview of the inflammatory mechanisms involved in neuralgia. It also examines recent advancements in research, exploring the influence of ion channels and synaptic proteins on neuralgia and its complications. Additionally, the interactions between these mechanisms are discussed with the aim of suggesting innovative therapeutic approaches and research directions for the management of neuralgia.

Significant response from fruquintinib plus anti-PD-1 immunotherapy for microsatellite stable metastatic colorectal cancer with liver and lung metastasis in the third line: case report.

Background: There are limited treatment options available for patients with metastatic colorectal cancer (mCRC). About 95% of CRC patients have mismatch repair proficient/microsatellite stable (pMMR/MSS) tumors are virtually unresponsive to programmed cell death protein 1 (PD-1) antibody treatment. This report shows that a patient with pMMR/MSS mCRC achieved significant response and the longest progression-free survival (PFS) of 28 months currently reported from tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor receptor (VEGFR) family (VEGFR-1,2,3) (fruquintinib) plus anti-PD-1 immunotherapy in the third line, providing a new and promising treatment option for some MSS mCRC patients. Case Description: This case details a 65-year-old male with CRC who was diagnosed with pT4aN2bM0, IIIC, and pMMR/MSS after curative surgery in August 2018. Subsequently, he received adjuvant chemotherapy [FOLFOX (folinic acid, fluorouracil, and oxaliplatin) for 5 cycles], first-line treatment (pelvic radiation plus capecitabine), and second-line treatment [TOMIRI (raltitrexed and irinotecan) plus cetuximab for 2 cycles]. Lung, liver, and pelvic cavity metastases worsened in October 2019. He began receiving the fruquintinib plus PD-1 inhibitor (FP) regimen as third-line treatment and after 3 cycles, the size of the lung lesions was significantly reduced and evaluated as partial response (PR), whereas the liver and pelvic cavity lesions remained stable. As of December 2021, he had received a total of 33 courses of FP regimen. In February 2022, liver metastases progressed. In brief, he achieved a long PFS of 28 months and an overall survival (OS) of 40 months from the third-line treatment. Additionally, the patient only experienced mild proteinuria after the combined treatment and tolerated well. Conclusions: Fruquintinib combined with immunotherapy could exert good therapeutic effects with safety in MSS mCRC patients. And patients with lung metastasis may be the principal beneficiaries.

The Efficacy and Safety of Sintilimab Combined With Nab-Paclitaxel as a Second-Line Treatment for Advanced or Metastatic Gastric Cancer and Gastroesophageal Junction Cancer.

Background: Unresectable advanced or recurrent gastric cancer patients have a poor prognosis. PD-1 monotherapy regimen and PD-1 combined chemotherapy regimen have become the standard third- and first-line treatment for advanced gastric cancer, respectively. However, the status of immune checkpoint inhibitors in the second-line treatment for advanced gastric cancer has not been established. The combination of chemotherapy and anti-PD-1 antibody has been demonstrated to have a synergistic effect. In this study, we aimed to evaluate the efficacy and safety of sintilimab combined with nab-paclitaxel in the second-line treatment for advanced gastric cancer (GC)/gastroesophageal junction (GEJ) cancer patients. Patients and Methods: We retrospectively analyzed patients with advanced GC/GEJ cancer that progressed after first-line systemic therapies with sintilimab combined with nab-paclitaxel from April 1, 2019 to December 31, 2021. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. Results: Thirty-nine patients were enrolled and eligible for response assessment. Complete response (CR) was not observed, 15 patients achieved partial response (PR), 16 patients had stable disease (SD) and 9 patients had progressive disease (PD). The ORR and DCR were 15 (38.5%) and 31 (79.5%), respectively. Median PFS was 5.4 months (95%CI: 3.072-7.728). PFSs between different subgroups were analyzed. The results showed that gender, age, Human epidermal growth factor receptors 2 (HER2) status, PD-L1 expression, primary tumor site and chemotherapy cycles had no significant effect on PFS. Most of the adverse events (AEs) were of grade 1-2 and manageable. The common treatment-related adverse events of grade 3 or 4 included anemia (12.8%), neutropenia (12.8%), leukopenia (10.3%), hand-foot syndrome (7.7%), thrombocytopenia (7.7%). The potential immune-related adverse events (irAEs) were grade 1 pneumonia (1 pts [2.6%]) and grade 4 hepatitis (1 pts [2.6%]). There were no treatment-related deaths. Conclusion: These results indicate that sintilimab combined with nab-paclitaxel exhibits good anti-tumor activity and an acceptable safety profile as a second-line treatment for advanced or metastatic gastric cancer. These results warrant further investigation and evaluation to identify patients who can benefit more from the combined treatment strategy.

Fruquintinib Enhances the Antitumor Immune Responses of Anti-Programmed Death Receptor-1 in Colorectal Cancer.

Background: Programmed death receptor-1 (PD-1) blockade shows little benefit in patients with microsatellite-stable colorectal cancer (MSS-CRC). Fruquintinib is a China-made anti-angiogenic drug which is approved for the third line therapy in mCRC. This study investigates the effect of the combination of fruquintinib and PD-1 blockade on MSS-CRC and its relative mechanisms. Methods: The mouse allograft tumor models that represent MSS and microsatellite instability (MSI) CRC were established using murine CT26 and MC38 colon cancer cells, respectively, to assess the treatment efficacy. The percentages of immune cells were detected in the peripheral blood, spleen and tumor tissues in the tumor-bearing mice by flow cytometry analysis. Angiogenesis in tumor tissues was detected by immunofluorescence. The safety of drug treatment was evaluated by histopathology analysis in murine main organs. The efficacy of the combination of fruquintinib and sintilimab were verified in the treatment of MSS-CRC patients. Results: Our results showed that the combination of fruquintinib and sintilimab exhibited the strongest inhibition of tumor growth and achieved the longest survival time in mice bearing MC38 or CT26 xenograft tumors, compared to fruquintinib and sintilimab alone. Mechanistically, the combination of fruquintinib and sintilimab reduced angiogenesis, reprogramed the vascular structure, enhanced the infiltration of CD8+T cells (p<0.05), CD8+TNFα+ (p<0.05) T cells and CD8+IFNγ+ (p<0.05) T cells and reduced the ratios of MDSCs and macrophages in mice. There was no obvious toxicity observed in the main organs of the tumor-bearing mice with the combined treatment. Moreover, the treatment using the combination of fruquintinib and sintilimab achieved effective response in five patients with refractory advanced MSS CRC. Conclusion: Our results show that the combination of fruquintinib and sintilimab greatly inhibits CRC growth by altering tumor immune microenvironment. This study provides the rational for using the combination of fruquintinib and anti-PD-1 antibody for the treatment of advanced CRC.

Retrospective Study on the Efficacy and Safety of Pyrotinib-Based Therapy for HER2-Positive Nonbreast Advanced Solid Tumors.

Background: Human epidermal growth factor receptor 2 (HER2) is a member of the large ErbB family and an important oncogene in many solid tumors. Pyrotinib has been approved for the treatment of HER2-positive, recurrent, or metastatic breast cancer. However, there are very few clinical studies on pyrotinib in other HER2-positive solid tumors. Therefore, more evidence of clinical research is impendently needed to shepherd pyrotinib-based therapy in HER2-positive nonbreast advanced solid tumors. Patients and Methods. We performed a retrospective analysis of HER2-positive nonbreast advanced solid tumors patients with HER2 amplification or mutations who were administered with pyrotinib-based therapy in Henan Cancer Hospital between July 1, 2019, and December 2, 2021. In our research, 25 eligible patients were included with 16 patients with lung cancer, 6 patients with gastric cancer, 2 patients with colorectal cancer, and 1 patient with cholangiocarcinoma. Progression-free survival (PFS) is our main research end point. Results: The median PFS was 188 days (95% CI: 83-not reached (NR)), and overall survival (OS) was 250 days (95% CI: 188-NR), respectively. 16 patients with lung cancer had a median PFS of 204 days (95% CI: 55-NR) and 6 patients with gastric cancer had PFS of 142 days (95% CI: 83-NR), respectively. The median OS was 366 days (95% CI: 248-NR) in patients with lung cancer and 179 days (95% CI: 90-NR) in patients with gastric cancer. The median PFS and OS of patients receiving >3 line treatment were lower than those receiving ≤3 line treatment (PFS: 188 days vs 204 days, p = 0.92; OS: 188 days vs 366 days, p = 0.43). All 25 patients can be evaluated. The objective response rate (ORR) was 24%, and the disease control rate (DCR) was 68%. Lung cancer ORR was 25%, and gastric cancer ORR was 16.7%. In addition, the DCR of lung cancer was 62.5% and that of gastric cancer was 66.7%. In addition, the ORR and DCR of patients receiving treatment ≤3 lines were higher than those receiving treatment >3 lines (ORR: 35.7% vs 9.1%, p = 0.18; DCR: 71.4% vs 63.6%, p > 0.99). The most common treatment-related adverse events (TRAEs) were diarrhea (84%), but only 3 patients (12%) reported grade 3 diarrhea with good control. Conclusion: These results show that in HER2-positive nonbreast advanced solid tumors, the treatment based on pyrotinib regimen has good antitumor activity and acceptable safety. This retrospective study aims to promote larger clinical studies to further clarify the efficacy and safety of pyrotinib in the treatment of nonbreast solid tumors.

Concordance of Alzheimer's Disease Subtypes Produced from Different Representative Morphological Measures: A Comparative Study.

BACKGROUND: Gray matter (GM) density and cortical thickness (CT) obtained from structural magnetic resonance imaging are representative GM morphological measures that have been commonly used in Alzheimer's disease (AD) subtype research. However, how the two measures affect the definition of AD subtypes remains unclear. METHODS: A total of 180 AD patients from the ADNI database were used to identify AD subgroups. The subtypes were identified via a data-driven strategy based on the density features and CT features, respectively. Then, the similarity between the two features in AD subtype definition was analyzed. RESULTS: Four distinct subtypes were discovered by both density and CT features: diffuse atrophy AD, minimal atrophy AD (MAD), left temporal dominant atrophy AD (LTAD), and occipital sparing AD. The matched subtypes exhibited relatively high similarity in atrophy patterns and neuropsychological and neuropathological characteristics. They differed only in MAD and LTAD regarding the carrying of apolipoprotein E ε2. CONCLUSIONS: The results verified that different representative morphological GM measurement methods could produce similar AD subtypes. Meanwhile, the influences of apolipoprotein E genotype, asymmetric disease progression, and their interactions should be considered and included in the AD subtype definition. This study provides a valuable reference for selecting features in future studies of AD subtypes.

Multi-model and multi-slice ensemble learning architecture based on 2D convolutional neural networks for Alzheimer's disease diagnosis.

Alzheimer's Disease (AD) is a chronic neurodegenerative disease without effective medications or supplemental treatments. Thus, predicting AD progression is crucial for clinical practice and medical research. Due to limited neuroimaging data, two-dimensional convolutional neural networks (2D CNNs) have been commonly adopted to differentiate among cognitively normal subjects (CN), people with mild cognitive impairment (MCI), and AD patients. Therefore, this paper proposes an ensemble learning (EL) architecture based on 2D CNNs, using a multi-model and multi-slice ensemble. First, the top 11 coronal slices of grey matter density maps for AD versus CN classifications were selected. Second, the discriminator of a generative adversarial network, VGG16, and ResNet50 were trained with the selected slices, and the majority voting scheme was used to merge the multi-slice decisions of each model. Afterwards, those three classifiers were used to construct an ensemble model. Multi-slice ensemble learning was designed to obtain spatial features, while multi-model integration reduced the prediction error rate. Finally, transfer learning was used in domain adaptation to refine those CNNs, moving them from working solely with AD versus CN classifications to being applicable to other tasks. This ensemble approach achieved accuracy values of 90.36%, 77.19%, and 72.36% when classifying AD versus CN, AD versus MCI, and MCI versus CN, respectively. Compared with other state-of-the-art 2D studies, the proposed approach provides an effective, accurate, automatic diagnosis along the AD continuum. This technique may enhance AD diagnostics when the sample size is limited.

Utidelone inhibits growth of colorectal cancer cells through ROS/JNK signaling pathway.

Utidelone (UTD1), a novel microtubule stabilizing agent, is an epothilone B analogue which was produced by genetic engineering. UTD1 has exhibited broad antitumor activity in multiple solid tumors. However, its activity and mechanism in colorectal cancer (CRC) remain to be studied. In this study, UTD1 dramatically inhibited CRC cell proliferation (with 0.38 µg/ml, 0.77 µg/ml IC50 in RKO and HCT116, respectively) in vitro. Immunofluorescence staining showed that UTD1 induced the formation of microtubule bundling and asters in RKO cells. Flow cytometry analysis demonstrated that UTD1 induced cell cycle to arrest in G2/M phase, subsequent apoptosis. Significantly, UTD1 exhibited stronger effect on inducing apoptosis than paclitaxel and 5-FU, especially in HCT15 cells which is ABCB1 high-expression. UTD1 exposure cleaved caspase-3 and poly ADP-ribose polymerase (PARP), decreased mitochondrial membrane potential, released cytochrome c, increased the production of active oxygen and activated c-Jun N-terminal kinase (JNK), suggesting ROS/JNK pathway was involved in this process. Moreover, UTD1 inhibited tumor growth and was more effective and safer compared with paclitaxel and 5-FU in RKO xenograft in nude mice. Taken together, our findings first indicate that UDT1 inhibits tumor growth in CRC xenograft model and may be a promising agent for CRC treatment.

Wnt Inhibition Sensitizes PD-L1 Blockade Therapy by Overcoming Bone Marrow-Derived Myofibroblasts-Mediated Immune Resistance in Tumors.

Cancer-associated fibroblasts (CAFs) has been recognized as one cause of tumor resistance to immune checkpoint blockade therapy, but the underlying mechanisms still remain elusive. In the present study, a bone marrow-derived CAF (BMF) -rich tumor model is successfully established by subcutaneously mixed inoculation of BMFs and tumor cells into mice and the BMF-mixed tumor xenografts are demonstrated to be resistant to anti-PD-L1 antibody immunotherapy compared to the mere tumor xenografts. In vitro assays via the co-culture system of BMFs and tumor cells indicate that the co-cultured BMFs are induced to overexpress PD-L1, while there is no such a phenomenon in the co-cultured cancer cells. The further knock-out of PD-L1 in BMFs rescues the sensitivity of BMF-mixed tumor xenografts to PD-L1 blockade therapy. Mechanistically, via the microarray assay, we identify that the upregulation of PD-L1 in BMFs stimulated by cancer cells is medicated by the activation of the Wnt/ß-catenin signaling pathway in BMFs. Moreover, the administration of Wnt/ß-catenin signaling inhibitors, including XAV-939 and Wnt-C59, distinctly inhibits the upregulation of PD-L1 expression in the co-cultured BMFs. The further combination administration of XAV-939 significantly potentiates the therapeutic outcome of PD-L1 blockade therapy in BMF-mixed tumors. In summary, our study demonstrates that Wnt inhibition augments PD-L1 blockade efficacy by overcoming BMF-mediated immunotherapy resistance.

Multiple Subtypes of Alzheimer's Disease Base on Brain Atrophy Pattern.

Alzheimer's disease (AD) is a disease of a heterogeneous nature, which can be disentangled by exploring the characteristics of each AD subtype in the brain structure, neuropathology, and cognition. In this study, a total of 192 AD and 228 cognitively normal (CN) subjects were obtained from the Alzheimer's disease Neuroimaging Initiative database. Based on the cortical thickness patterns, the mixture of experts method (MOE) was applied to the implicit model spectrum of transforms lined with each AD subtype, then their neuropsychological and neuropathological characteristics were analyzed. Furthermore, the piecewise linear classifiers composed of each AD subtype and CN were resolved, and each subtype was comprehensively explained. The following four distinct AD subtypes were discovered: bilateral parietal, frontal, and temporal atrophy AD subtype (occipital sparing AD subtype (OSAD), 29.2%), left temporal dominant atrophy AD subtype (LTAD, 22.4%), minimal atrophy AD subtype (MAD, 16.1%), and diffuse atrophy AD subtype (DAD, 32.3%). These four subtypes display their own characteristics in atrophy pattern, cognition, and neuropathology. Compared with the previous studies, our study found that some AD subjects showed obvious asymmetrical atrophy in left lateral temporal-parietal cortex, OSAD presented the worst cerebrospinal fluid levels, and MAD had the highest proportions of APOE ε4 and APOE ε2. The subtype characteristics were further revealed from the aspect of the model, making it easier for clinicians to understand. The results offer an effective support for individual diagnosis and prognosis.

A Review of Brain Atrophy Subtypes Definition and Analysis for Alzheimer's Disease Heterogeneity Studies.

Alzheimer's disease (AD) is a heterogeneous disease with different subtypes. Studying AD subtypes from brain structure, neuropathology, and cognition are of great importance for AD heterogeneity research. Starting from the study of constructing AD subtypes based on the features of T1-weighted structural magnetic resonance imaging, this paper introduces the major connections between the subtype definition and analysis strategies, including brain region-based subtype definition, and their demographic, neuropathological, and neuropsychological characteristics. The advantages and existing problems are analyzed, and reasonable improvement schemes are prospected. Overall, this review offers a more comprehensive view in the field of atrophy subtype in AD, along with their advantages, challenges, and future prospects, and provide a basis for improving individualized AD diagnosis.

Bone Marrow-Derived Myofibroblasts Promote Gastric Cancer Metastasis by Activating TGF-ß1 and IL-6/STAT3 Signalling Loop.

BACKGROUND: Murine bone marrow-derived myofibroblasts (BMFs) have previously been shown to promote gastric cancer growth. However, whether BMFs promote gastric cancer cell metastasis remains largely unknown. METHODS: Wound healing assay, Transwell invasion and migration assay and 3D organotypic co-culture systems were conducted to study the effects of BMFs on invasion and migration of gastric cancer cells and the invasion and migration ability of gastric cancer stem cell-like cells (CSC-LCs) induced by BMFs. We employed two animal model to study the role of BMFs on the in vivo metastasis of gastric cancer cells and the metastatic ability of gastric BMF-induced CSC-LCs. A human gastric cancer tissue microarray and TCGA gastric cancer database were analysed to study the relationship between the expression of IL-6 and TGF-ß1 and clinicopathological characteristics and survival in gastric cancer. RESULTS: We found that BMFs promoted the in vitro migration and invasion of gastric cancer cells. BMFs promoted liver, lung, subcutaneous, and splenic metastases of MKN28 cells in the spleen injection liver metastasis model and co-injection of caudal vein (IOCV) mouse model. BMFs reprogrammed non-gastric cancer stem cell (CSC) to CSC-LCs and enhanced CSC-LC migration and metastasis. BMF-derived IL-6 and gastric cancer cell-secreted TGF-ß1 mediated the interaction between BMFs and gastric cancer cells, promoting tumour metastasis. BMFs enhanced the expressions of STAT3 and p-STAT3 in co-cultured gastric cancer cells. A combination of Napabucasin and Galunisertib exhibited the strongest inhibition of cell migration compared to when administered alone. Gastric cancer tissue array and TCGA database indicated that the overexpression of IL-6 and TGF-ß1 was associated with gastric cancer metastasis. CONCLUSION: Our results demonstrated that BMFs promote gastric cancer metastasis through the activation of the TGF-ß1 and IL-6/STAT3 signalling pathways. Targeting the inhibition of these interactions may be a potent therapeutic strategy for addressing gastric cancer metastasis.

Evaluation of five diffeomorphic image registration algorithms for mouse brain magnetic resonance microscopy.

The development of genetically engineered mouse models for neuronal diseases and behavioural disorders have generated a growing need for small animal imaging. High-resolution magnetic resonance microscopy (MRM) provides powerful capabilities for noninvasive studies of mouse brains, while avoiding some limits associated with the histological procedures. Quantitative comparison of structural images is a critical step in brain imaging analysis, which highly relies on the performance of image registration techniques. Nowadays, there is a mushrooming growth of human brain registration algorithms, while fine-tuning of those algorithms for mouse brain MRMs is rarely addressed. Because of their topology preservation property and outstanding performance in human studies, diffeomorphic transformations have become popular in computational anatomy. In this study, we specially tuned five diffeomorphic image registration algorithms [DARTEL, geodesic shooting, diffeo-demons, SyN (Greedy-SyN and geodesic-SyN)] for mouse brain MRMs and evaluated their performance using three measures [volume overlap percentage (VOP), residual intensity error (RIE) and surface concordance ratio (SCR)]. Geodesic-SyN performed significantly better than the other methods according to all three different measures. These findings are important for the studies on structural brain changes that may occur in wild-type and transgenic mouse brains.

Predicting healthy older adult's brain age based on structural connectivity networks using artificial neural networks.

Brain ageing is followed by changes of the connectivity of white matter (WM) and changes of the grey matter (GM) concentration. Neurodegenerative disease is more vulnerable to an accelerated brain ageing, which is associated with prospective cognitive decline and disease severity. Accurate detection of accelerated ageing based on brain network analysis has a great potential for early interventions designed to hinder atypical brain changes. To capture the brain ageing, we proposed a novel computational approach for modeling the 112 normal older subjects (aged 50-79 years) brain age by connectivity analyses of networks of the brain. Our proposed method applied principal component analysis (PCA) to reduce the redundancy in network topological parameters. Back propagation artificial neural network (BPANN) improved by hybrid genetic algorithm (GA) and Levenberg-Marquardt (LM) algorithm is established to model the relation among principal components (PCs) and brain age. The predicted brain age is strongly correlated with chronological age (r=0.8). The model has mean absolute error (MAE) of 4.29 years. Therefore, we believe the method can provide a possible way to quantitatively describe the typical and atypical network organization of human brain and serve as a biomarker for presymptomatic detection of neurodegenerative diseases in the future.