Colorectal cancer (CRC) is the third most common malignant cancer worldwide with the second highest mortality. Gut microbiota can educate the tumor microenvironment (TME), consequently influencing ...the efficacy of immune checkpoint inhibitors (ICIs). Fusobacterium
is one of the most crucial bacteria contributing to colorectal tumorigenesis, but the molecular mechanisms between
and TME or ICIs are poorly investigated. In the present study, we firstly analyzed differentially expressed genes and the biological functions between
-infected and uninfected CRC cell lines, with the findings that CCL22 mRNA expression was markedly upregulated after
infection. Moreover, the survival analysis showed that CCL22 was significantly associated with the overall survival of CRC patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis suggested that CCL22 was related to immune-related terms. Furthermore, the ESTIMATE analysis indicated that the high-CCL22-expression subgroup had a higher immune/stromal/estimate score and lower tumor purity. The CIBERSORT analysis indicated that the high-CCL22-expression group had more immune-suppressive cells and less antitumor immune cells. In addition, immune checkpoint genes and cytotoxic genes were positively correlated with CCL22 expression. The immunophenoscore analysis suggested that CCL22 was associated with the IPS-CTLA4 and PD1/PD-L1/PD-L2 score. Interestingly, CCL22 expression in the KRAS and APC mutation groups was markedly reduced compared to that of the wild groups. In summary, our study provided evidence that CCL22 might play a crucial role in
-related colorectal tumorigenesis and correlate with TME and ICIs, which deserves further study.
The substantial rise in the population of older adults living with disabilities is a prominent concern, presenting a profound challenge for healthcare and social welfare systems. Community-based home ...care is seen as an effective approach to meet the care needs of older adults living with disabilities.
To construct a coping target checklist for home-based older adults living with disabilities and their spousal caregivers.
The initial draft was developed based on a comprehensive literature review, followed by two rounds of Delphi correspondence final version.
A comprehensive literature review resulted in the development of 7 modules, 20 topics. After round 1, 3 items were removed, 3 sections, 1 topic and 1 objective were new additions, 16 items were modified, split or combined. Four sections, 3 sections (Individual coping target for spousal caregivers, Individual coping target for older adults living with disabilities, and Shared coping target), 7 modules, 18 topics and 49 objectives were finally identified in round 2. The content of the list tool is derived from three perspectives: self-management strategies for older adults living with disabilities, caregiving strategies for spousal caregivers, and combined.
The coping target checklist was intended to be evidence-based and reflective of a practical direction for home-based older adults living with disabilities and their spousal caregivers living at home.
Bi
5
Ti
3
FeO
15
ferroelectric nanosheets are synthesized by molten salt method and further decorated Au nanoparticles on the surface of nanosheets by chemical reduced method. The phase structure, ...morphology, and optical properties of the samples are characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and UV–vis spectroscopy, respectively. The introducing Au nanoparticles in Bi
5
Ti
3
FeO
15
photocatalyst significantly improved light absorption and inhibit recombination of photo-generated electron/hole pairs due to the typical LSPR effect and the interface effect. The Au/Bi
5
Ti
3
FeO
15
composite photocatalyst exhibited superior photocatalyst activities for NO removal and excellent stability photocatalyst performance compared with the Bi
5
Ti
3
FeO
15
. The results of Density functional theory (DFT) confirm that the formation of ohmic contact between Bi
5
Ti
3
FeO
15
and Au, which improve the ability of electron transfer and oxygen activation. Thus, the efficiency of separation of photo-induced
e
−
/
h
+
pairs and the generation of ⋅O
2
−
and ⋅OH species are promoted. The scavenger experiments measurements reveal that
e
−
play the most critical role,
h
+
and ·OH serve as a secondary active species in the photocatalytic activity for NO removal. Furthermore, the NO removal reaction process on the surface of the Au/Bi
5
Ti
3
FeO
15
photocatalyst is studied by
in-situ
FTIR spectroscopy. This research provides a feasible idea to construct photocatalyst with high efficiency activity via decorating noble metal on ferroelectric materials.
Graphical Abstract
Rationale, aims, and objectives
Valid and reliable instruments for measuring are needed. To add knowledge to the subject of tools of evidence‐based practice (EBP) evaluation in mainland China, the ...present study aims to translate the Quick‐EBP‐VIK into Chinese, which is an instrument for the assessment of nurses' value, knowledge, and implementation of EBP, and to evaluate the metric characteristics of the Chinese version.
Methods
In this methodological study, a total sample of 402 nurses from mainland China was applied. Construct validity was evaluated by using factor analysis and further supported through known‐group validity. A panel of experts examined the content validity. Internal consistency was determined using composite reliability and Cronbach alpha. The intraclass correlation coefficient (ICC) was calculated to assess test‐retest reliability.
Results
The exploratory factor analysis revealed a three‐factor structure model same to the original instrument. The confirmatory factor analysis showed a good fit model with a comparative fit index of 0.957 and a root mean square error of approximation of 0.065. Significant differences were found in the item means of the tool between nurses who received EBP training and those who had not, which supported the known‐group validity. The Cronbach alpha and composite reliability for the three subscales were all higher than 0.70. The ICC ranged from 0.569 to 0.928 for the three subscales and from 0.494 to 0.903 for the items included in the instrument.
Conclusion
The Chinese version of the Quick‐EBP‐VIK has evidence of acceptable reliability and validity and can be used to measure value, knowledge, and implementation of EBP for Chinese nurses.
Mirror visual feedback (MVF) has been widely used in neurological rehabilitation. Due to the potential gain effect of the MVF combination therapy, the related mechanisms still need be further ...analyzed.
Our self-controlled study recruited 20 healthy subjects (age 22.150 ± 2.661 years) were asked to perform four different visual feedback tasks with simultaneous functional near infrared spectroscopy (fNIRS) monitoring. The right hand of the subjects was set as the active hand (performing active movement), and the left hand was set as the observation hand (static or performing passive movement under soft robotic bilateral hand rehabilitation system). The four VF tasks were designed as RVF Task (real visual feedback task), MVF task (mirror visual feedback task), BRM task (bilateral robotic movement task), and MVF + BRM task (Mirror visual feedback combined with bilateral robotic movement task).
The beta value of the right pre-motor cortex (PMC) of MVF task was significantly higher than the RVF task (RVF task: -0.015 ± 0.029, MVF task: 0.011 ± 0.033,
= 0.033). The beta value right primary sensorimotor cortex (SM1) in MVF + BRM task was significantly higher than MVF task (MVF task: 0.006 ± 0.040, MVF + BRM task: 0.037 ± 0.036,
= 0.016).
Our study used the synchronous fNIRS to compare the immediate hemodynamics cortical activation of four visual feedback tasks in healthy subjects. The results showed the synergistic gain effect on cortical activation from MVF combined with a soft robotic bilateral hand rehabilitation system for the first time, which could be used to guide the clinical application and the future studies.
Background:
KRAS mutation, one of the most important biological processes in colorectal cancer, leads to poor prognosis in patients. Although studies on KRAS have concentrated for a long time, there ...are currently no ideal drugs against KRAS mutations.
Methods:
Different expression analysis and weighted gene coexpression network analysis was conducted to select candidate genes. Log-rank tests and Cox regression picked out the prognostic genes to build a KRAS-related gene prognostic score (KRGPS). A nomogram based on KRGPS was built to predict survival of clinical patients. Comprehensive analysis showed the prognosis, immune microenvironment and response to immune therapy and chemotherapy in KRGPS subgroups.
Results:
We collected a KRGPS from the set of two genes GJB6 and NTNG1, with low-KRGSP patients having better progression-free survival (PFS). Low KRGPS is correlated with high infiltration of activated NK cells, plasma cells and activated memory CD4 T cells and that these cells benefit more from immune checkpoint inhibitor therapy. However, high KRGPS is associated with high infiltration of activated mast cells, pathways of immune dysregulation and a high ratio of TP53 and KRAS mutations. KRGPS subgroups are also sensitive to chemotherapy differently. A nomogram, established based on the KRGPS and pathological stage, predict 3- and 5-years PFS well.
Conclusions:
The KRAS-associated score acts as a promising signature to distinguish prognosis, molecular and immune characteristics, and benefits from immune and chemical therapy. These KRAS-associated genes could be promising targets for drug design.
The motor imagery brain computer interface (MI-BCI) is now available in a commercial product for clinical rehabilitation. However, MI-BCI is still a relatively new technology for commercial ...rehabilitation application and there is limited prior work on the frequency effect. The MI-BCI has become a commercial product for clinical neurological rehabilitation, such as rehabilitation for upper limb motor dysfunction after stroke. However, the formulation of clinical rehabilitation programs for MI-BCI is lack of scientific and standardized guidance, especially limited prior work on the frequency effect. Therefore, this study aims at clarifying how frequency effects on MI-BCI training for the plasticity of the central nervous system.
Sixteen young healthy subjects (aged 22.94 ± 3.86 years) were enrolled in this randomized clinical trial study. Subjects were randomly assigned to a high frequency group (HF group) and low frequency group (LF group). The HF group performed MI-BCI training once per day while the LF group performed once every other day. All subjects performed 10 sessions of MI-BCI training. functional near-infrared spectroscopy (fNIRS) measurement, Wolf Motor Function Test (WMFT) and brain computer interface (BCI) performance were assessed at baseline, mid-assessment (after completion of five BCI training sessions), and post-assessment (after completion of 10 BCI training sessions).
The results from the two-way ANOVA of beta values indicated that GROUP, TIME, and GROUP × TIME interaction of the right primary sensorimotor cortex had significant main effects GROUP:
= 7.251,
= 0.010; TIME:
= 3.317,
= 0.046; GROUP × TIME:
= 5.676,
= 0.007. The degree of activation was affected by training frequency, evaluation time point and interaction. The activation of left primary sensory motor cortex was also affected by group (frequency) (
= 0.003). Moreover, the TIME variable was only significantly different in the HF group, in which the beta value of the mid-assessment was higher than that of both the baseline assessment (
= 0.027) and post-assessment (
= 0.001), respectively. Nevertheless, there was no significant difference in the results of WMFT between HF group and LF group.
The major results showed that more cortical activation and better BCI performance were found in the HF group relative to the LF group. Moreover, the within-group results also showed more cortical activation after five sessions of BCI training and better BCI performance after 10 sessions in the HF group, but no similar effects were found in the LF group. This pilot study provided an essential reference for the formulation of clinical programs for MI-BCI training in improvement for upper limb dysfunction.
Despite immune checkpoint blockade (ICB) therapy contributed to significant advances in cancer therapy, only a small percentage of patients with colorectal cancer (CRC) respond to it. Identification ...of these patients will facilitate ICB application in CRC. In this study, we integrated multiple CRC cohorts (2,078 samples) to construct tumor microenvironment (TME) subtypes using TME indices calculated by CIBERSORT and ESTIMATE algorithms. Furthermore, a surrogate quantitative indicator, a tumor microenvironment immune gene (TMEIG) score system, was established using the key immune genes between TME clusters 1 and 2. The subsequent analysis demonstrated that TME subtypes and the TMEIG score system correlated with clinical outcomes of patients in multiple CRC cohorts and exhibited distinct immune statuses. Furthermore, Tumor Immune Dysfunction and Exclusion (TIDE) analysis indicated that patients with low TMEIG scores were more likely to benefit from ICB therapy. A study on two ICB cohorts (GSE78220 and IMvigor210) also validated that patients with low TMEIG scores exhibited higher ICB response rates and better prognoses after ICB treatment. The biomarker evaluation module on the TIDE website revealed that the TMEIG score was a robust predictive biomarker. Moreover, differential expression analysis, immunohistochemistry, qPCR experiments, and gene set prioritization module on the TIDE website demonstrated that the five genes that constitute the TMEIG score system (
SERPINE1
,
FABP4
,
SCG2
,
CALB2
, and
HOXC6
) were closely associated with tumorigenesis, immune cells, and ICB response indices. Finally, TMEIG scores could accurately predict the prognosis and ICB response of patients with CRC.
SERPINE1
,
FABP4
,
SCG2
,
CALB2
, and
HOXC6
might be potential targets related to ICB treatment. Furthermore, our study provided new insights into precision ICB therapy in CRC.
No effective treatments can ameliorate symptoms of long COVID patients. Our study assessed the safety and efficacy of human umbilical cord‐derived mesenchymal stem cells (UC‐MSCs) in the treatment of ...long COVID patients. Ten long COVID patients were enrolled and received intravenous infusions of UC‐MSCs on Days 0, 7, and 14. Adverse events and clinical symptoms were recorded, and chest‐high‐resolution CT (HRCT) images and laboratory parameters were analyzed. During UC‐MSCs treatment and follow‐up, we did not observe serious adverse events, the symptoms of long COVID patients were significantly relieved in a short time, especially sleep difficulty, depression or anxiety, memory issues, and so forth, and the lung lesions were also repaired. The routine laboratory parameters did not exhibit any significant abnormalities following UC‐MSCs transplantation (UMSCT). The proportion of regulatory T cells gradually increased, but it was not statistically significant until 12 months. The proportion of naive B cells was elevated, while memory B cells, class‐switched B‐cells, and nonswitched B‐cells decreased at 1 month after infusion. Additionally, we observed a transient elevation in circulating interleukin (IL)−6 after UMSCT, while tumor necrosis factor (TNF)‐α, IL‐17A, and IL‐10 showed no significant changes. The levels of circulating immunoglobulin (Ig) M increased significantly at month 2, while IgA increased significantly at month 6. Furthermore, the SARS‐CoV‐2 IgG levels remained consistently high in all patients at Month 6, and there was no significant decrease during the subsequent 12‐month follow‐up. UMSCT was safe and tolerable in long COVID patients. It showed potential in alleviating long COVID symptoms and improving interstitial lung lesions.
Due to its high biosafety, gellan gum (GG) hydrogel, a naturally occurring polysaccharide released by microorganisms, is frequently utilized in food and pharmaceuticals. In recent years, like GG, ...natural polysaccharide-based hydrogels have become increasingly popular in 3D-printed biomedical engineering because of their simplicity of processing, considerable shear thinning characteristic, and minimal pH dependence. To mitigate the negative effects of the GG's high biological inertia, poor cell adhesion, single cross-linked network, and high brittleness. Mesoporous silica nanospheres (MMSN) and Aldehyde-based methacrylated hyaluronic acid (AHAMA) were combined to sulfhydrated GG (TGG) to create a multi-network AHAMA/TGG/MMSN hydrogel in this study. For this composite hydrogel system, the multi-component offers several crosslinking networks: the double bond in AHAMA can be photocrosslinked by activating the photoinitiator, aldehyde groups on its side chain can create Schiff base bonds with MMSN, while TGG can self-curing at room temperature. The AHAMA/TGG/MMSN hydrogel, with a mass ratio of 2:6:1, exhibits good cell adhesion, high strength and elasticity, and great printability. We believe that this innovative multi-network hydrogel has potential uses in tissue regeneration and biomedical engineering.
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