ObjectiveTo understand relationship between LIM kinase (LIMK) and colorectal cancer in order to provide research basis for metastasis, invasion, and targeted therapy of colorectal cancer.MethodThe relevant literatures about the research progress on the structural function of LIMK and its correlation with colorectal cancer in recent years were reviewed.ResultsThe LIMK and its factors in the ROCK/LIMK/cofilin and PAK/LIMK/cofilin pathways were involved in various cell biological behaviors such as the tumor cell cycle progression, tumor cell invasion, migration, and proliferation. For example, the p21-activated kinase 4 (PAK4) participated in the cytoskeletal dynamics to regulate cancer cell migration and invasion through the PAK4/LIMK1/cofilin signaling pathway. The cofilin affected the tumor cell movement and morphology through the Rho/ROCK/LIMK1/cofilin signaling pathway, thus then participated in the tumor cell invasion and migration. In addition, the studies had reported that two tumor metastasis-associated proteins, MYH9 and ACTN4, were the direct targets of LIMK1, and the three interactions could promote the colon cancer progression. Another member of the LIMK family: LIMK2, which inhibited the cell metastasis by limiting the epithelial mesenchymal transition (EMT) process, and the nuclear chain of β-catenin activated the Wnt signaling pathway, leading to the colon cancer progression and metastasis. Diallyl disulfide down-regulated the expression of LIMK1 in the colon cancer cells SW480, inhibited the LIMK1/cofilin signaling pathway, blocked angiogenesis and EMT, and inhibited the colon cancer migration and invasion, while others LIMK inhibitors had not been validated in the colorectal cancer.ConclusionsMolecular mechanism of colorectal cancer and its metastasis has not been fully elucidated. Through in-depth study of relationships between colorectal cancer and its metastasis mechanism and LIMK, it could provide a molecular targeted therapeutic breakthrough for colorectal cancer and its metastasis and more help for exploring of diagnosis, recurrence, prognosis and metastasis of colorectal cancer.
Objective To investigate the effect of microRNA-27a (miR-27a) on the apoptosis of human lung adenocarcinoma cells A549 induced by lipopolysaccharide (LPS) by regulating the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathway, and its mechanism is discussed preliminarily. Methods The complementary binding sites of miR-27a and phosphatidylinositol-3 kinase catalytic subunit delta (PIK3CD) were analyzed by Starbase and verified by double luciferase. The A549 cells were divided into normal group, LPS group, LPS+miR-27a mimic negative control group, LPS+miR-27a mimic group, LPS+miR-27a mimic+PI3K activator group. In the LPS+miR-27a mimic negative control group, LPS+miR-27a mimic group and LPS+miR-27a mimic+PI3K activator group, the cells were transfected with miR-27a mimic negative control, miR-27a mimic and miR-27a mimic, respectively, and were cultured for 6 h. After that, the cells were cultured in complete medium for 24 h, and then, except for the normal group, the cells in the other groups were stimulated with 10 mg/L LPS for 24 h, and the PI3K activator 740 Y-P was added to the LPS+miR-27a mimic+PI3K activator group, and cells in normal group were cultured in complete medium for the same time. Real-time quantitative polymerase chain reaction was used to detect the expression level of miR-27a in cells; cell counting kit 8 was used to detect cell proliferation; Hoechst33342 staining and flow cytometry was used to detect apoptosis; autophagy of A549 cells was observed by transmission electron microscope; Western blot was used to detect the expression of PIK3CD, phosphorylated-AKT (p-AKT), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3 and microtubule-associated protein 1 light chain 3 II (LC3II) protein. Results There was a binding site between miR-27a and PIK3CD, which was verified by double luciferase. Compared with those in normal group, the expression level of miR-27a, proliferation rate and protein expression level of Bcl-2 in LPS group and LPS+miR-27a mimic negative control group were lower (P<0.05), the apoptosis rate, protein expression levels of PIK3CD, p-AKT, Bax, cleaved caspase-3, LC3Ⅱ were higher (P<0.05); compared with those in LPS group and LPS+miR-27a mimic negative control group, the expression level of miR-27a, proliferation rate and protein expression level of Bcl-2 in LPS+miR-27a mimic group were higher (P<0.05), the apoptosis rate, protein expression levels of PIK3CD, p-AKT, Bax, cleaved caspase-3, LC3Ⅱ were lower (P<0.05); compared with those in LPS+miR-27a mimic group, the expression level of miR-27a and proliferation rate in LPS+miR-27a mimic+PI3K activator group were lower (P<0.05), the apoptosis rate, protein expression levels of PIK3CD, p-AKT, cleaved caspase-3, LC3Ⅱ were higher (P<0.05). The number of cells in the normal group was more, the cells were closely arranged, the nucleus size was uniform, and the organelle structure was normal; in LPS group and LPS+miR-27a mimic negative control group, cells became round, nuclei pyknosis, formed clumps, and showed multiple round autophagic vesicles of different sizes; the number of nuclear pyknotic cells in LPS+miR-27a mimic group decreased, and the number of nuclear pyknotic cells in LPS+miR-27a mimic+PI3K activator group increased compared with LPS+miR-27a mimic group, a small number of circular autophagic vesicles were observed, but the number was different. Conclusion Overexpression of miR-27a can inhibit PI3K/Akt pathway and reduce LPS induced apoptosis of human lung adenocarcinoma cells A549, which may be related to the reduction of autophagy.
Melanocytic lesions occur on the surface of the skin, in which the malignant type is melanoma with a high fatality rate, seriously endangering human health. The histopathological analysis is the gold standard for diagnosis of melanocytic lesions. In this study, a fully automated intelligent diagnosis method based on deep learning was proposed to classify the pathological whole slide images (WSI) of melanocytic lesions. Firstly, the color normalization based on CycleGAN neural network was performed on multi-center pathological WSI; Secondly, ResNet-152 neural network-based deep convolutional network prediction model was built using 745 WSI; Then, a decision fusion model was cascaded, which calculates the average prediction probability of each WSI; Finally, the diagnostic performance of the proposed method was verified by internal and external test sets containing 182 and 54 WSI, respectively. Experimental results showed that the overall diagnostic accuracy of the proposed method reached 94.12% in the internal test set and exceeded 90% in the external test set. Furthermore, the color normalization method adopted was superior to the traditional color statistics-based and staining separation-based methods in terms of structure preservation and artifact suppression. The results demonstrate that the proposed method can achieve high precision and strong robustness in pathological WSI classification of melanocytic lesions, which has the potential in promoting the clinical application of computer-aided pathological diagnosis.
ObjectiveTo explore the effects of cytokines on Febrile seizures (FS) in children with febrile seizures (Febrile seizures), febrile seizures duration and prognosis, and to explore the correlation between cytokines and the clinical manifestations and prognosis of FS. MethodsA retrospective analysis was performed on 121 children with FS (77 cases in the simple FS group and 44 cases in the complex FS group) who were treated in the pediatrics department of the Maternal and Child Health Hospital of Inner Mongolia Autonomous Region from January 2021 to October 2022 as the experimental group, including 71 males and 50 females, with a male-to-female ratio of 1.42:1, according to the type of attack (93 cases in the comprehensive group, 44 cases in the complex FS group). The focal group (28 cases) and convulsion duration (91 cases in <5 min group and 30 cases in ≥5 min group) were divided into groups, and 127 cases of children with fever but no convulsions were compared with the control group. In addition, 121 children with FS were followed up for 1 year by neurology specialist outpatient department and telephone follow-up. According to the follow-up, they were divided into the first course group, the relapse group and the secondary epilepsy group, so as to further explore the correlation between cytokines and the prognosis of children with FS. ResultsExperimental group compared with control group: Serum IL-1β (1.38 pg/mL), IL-2 (2.26 pg/mL), IL-4 (1.53 pg/mL), IL-6 (10.51 pg/mL), IL-10 (3.09 pg/mL), IL-12p70 (1.74 pg/mL), TNF-α (2.11 pg/mL), IFN-γ (46.56 pg/mL), IL-1β (1.38 pg/mL), IL-1β (1.26 pg/mL), IL-4 (1.53 pg/mL), IL-6 (10.51 pg/mL), IL-10 (3.09 pg/mL), IL-12P70 (1.74 pg/mL), TNF-α (2.11 pg/mL), IFN-γ (46.56 pg/mL). IFN-α (25.92 pg/mL) levels were higher, and the differences were statistically significant (P<0.05). There was no significant difference between the simple group and the complex group (P>0.05). <5 min group compared with control group: serum levels of IL-2 (2.32 pg/mL), IL-4 (1.53 pg/mL), IL-6 (9.65 pg/mL), IL-12p70 (1.74 pg/mL), TNF-α (2.11 pg/mL), IFN-γ (44.63 pg/mL), IFN-α (29.67 pg/mL) were higher, and the differences were statistically significant (P<0.05). Compared with control group, the levels of IL-2 (2.06 pg/mL), IL-6 (14.67 pg/mL), IL-12p70 (1.97 pg/mL), IFN-γ (58.56 pg/mL) and IFN-α (17.50 pg/mL) in ≥5 min group were higher, and the differences were statistically significant (P<0.05). ROC curve analysis showed that serum IFN-α had a high predictive value for FS onset, the cut-off point was 8.64pg/ml, and the sensitivity and specificity were 75.63% and 76.38%, respectively. There was no significant difference between the first course of disease group, relapse group and secondary epilepsy group. ConclusionSerum proinflammatory cytokines IL-1β, IL-2, IL-6, IL-12p70, TNF-α, IFN-γ, IFN-α and anti-inflammatory cytokines IL-4 and IL-10 are involved in the pathogenesis of FS. There was no correlation between the simplicity and complexity of serum cytokines. IL-2, IL-6, IL-12p70, IFN-γ, IFN-α were positively correlated with the duration of convulsion. When serum IFN-α>8.64 pg/ml, the possibility of FS attack increased.
Computed tomography (CT) imaging is a vital tool for the diagnosis and assessment of lung adenocarcinoma, and using CT images to predict the recurrence-free survival (RFS) of lung adenocarcinoma patients post-surgery is of paramount importance in tailoring postoperative treatment plans. Addressing the challenging task of accurate RFS prediction using CT images, this paper introduces an innovative approach based on self-supervised pre-training and multi-task learning. We employed a self-supervised learning strategy known as “image transformation to image restoration” to pretrain a 3D-UNet network on publicly available lung CT datasets to extract generic visual features from lung images. Subsequently, we enhanced the network’s feature extraction capability through multi-task learning involving segmentation and classification tasks, guiding the network to extract image features relevant to RFS. Additionally, we designed a multi-scale feature aggregation module to comprehensively amalgamate multi-scale image features, and ultimately predicted the RFS risk score for lung adenocarcinoma with the aid of a feed-forward neural network. The predictive performance of the proposed method was assessed by ten-fold cross-validation. The results showed that the consistency index (C-index) of the proposed method for predicting RFS and the area under curve (AUC) for predicting whether recurrence occurs within three years reached 0.691 ± 0.076 and 0.707 ± 0.082, respectively, and the predictive performance was superior to that of existing methods. This study confirms that the proposed method has the potential of RFS prediction in lung adenocarcinoma patients, which is expected to provide a reliable basis for the development of individualized treatment plans.
ObjectiveTo analyze the causes of unrelieved epilepsy thoroughly in children with isolated focal cortical dysplasia (FCD) based on MRI.MethodsRetrospective analysis of MRI and clinical data of 21 children with isolated FCD during July 2014 to January 2018, which confirmed by pathology and unrelieved thoroughly after operation performed, the pathological types and MRI signs were analyzed, as well as the frequency of different MRI signs in FCD of each pathological type. Analyzed the possible factors of surgical failure.ResultsAmong the 21 cases, there were 15 males and 6 females, with an average age of (5.7±0.3) years and an average course of disease of (3.4±0.5) years.MRI signs of this part of the children were mainly manifested by blurred focal gray matter boundaries, abnormal cortical structure changes (thickening and/or thinning), transmantle signs (abnormal cone signals extending from subcortical white matter to the ventricle) and abnormal gray matter signals, which were similar to MRI signs of FCD with satisfactory postoperative epilepsy control. 17 cases (80.9%) appeared epileptic discharge after operation in the EEG monitoring area 2 weeks to 6 months, FCD type I and type Ⅱ accounted for 35.3%, 64.7% respectively. During intraoperative EEG monitoring, no epileptiform discharge was observed in the transmantle sign region in 6 cases, and the region was retained, and only the surrounding abnormal discharge cortex was removed, complete removal of the tansmantle sign and surrounding abnormal discharge area was performed in 2 cases, and different degrees of epileptic epilepsy were observed in both methods.ConclusionMRI signs of isolated FCD with unrelieved epilepsy after operation were nonspecific, there were still epilepsy of varying degrees after all epileptogenic lesions have been removed, the cause may be related to potential epileptic factors.
ObjectiveTo summarize and analyze the clinical diagnosis, surgical treatment and prognosis of multiple pulmonary nodules (MPNs). Methods The clinical data of lung cancer patients who received surgical treatment in our hospital from 2018 to 2020 were collected. The short-term efficacy of surgical treatment for MPNs was analyzed. Results A total of 97 patients were enrolled, including 30 males and 67 females with an average age of 56.1±10.0 years at onset ill. There were 62 patients with double lesions, 22 patients with three lesions, 4 patients with four lesions, and 9 patients with more than four lesions. A total of 213 lesions were surgically treated, including 88 pure ground-glass nodules, 81 partially solid nodules, and 7 solid nodules. There were 87 simultaneous surgeries and 10 staged surgeries, with an average operation interval of 5.2 months. The pathological combination type included adenocarcinoma-adenocarcinoma in 96 (99.0%) patients, squamous cell carcinoma-squamous cell carcinoma in 1 (1.0%) patient, and no lymph node metastasis was found. The 2-year disease-free survival (DFS) rate was 92.1%, and the overall survival (OS) rate was 100.0%. Univariate analysis showed that high-risk lesion size>2 cm (P=0.316), residual lesions (P=0.782) and pathological combination type (P=0.913) had statistical effect on the 2-year DFS rate. Conclusion MPNs are mainly diagnosed with multiple primary lung cancers, and the pathological combination is mostly adenocarcinoma-adenocarcinoma combination. Imaging examination is of great help to the surgical approach selection, diagnosis and differential diagnosis of MPNs. During the operation, maximal preservation of lung function and complete resection of high-risk nodules should be taken as the principle, and the prognosis is satisfactory.
ObjectiveTo explore the best neoadjuvant treatment strategy for esophageal cancer and provide a theoretical basis for clinical formulation of neoadjuvant treatment plan. MethodsPubMed, EMbase, The Cochrane Library, Web of Science, CNKI, Wanfang, and VIP were searched from inception to May 2022. Two researchers independently performed literature screening and data extraction. The quality of the studies was evaluated by the Cochrane risk of bias tool, and data analysis was performed in RStudio environment using R3.6.3 software. ResultsA total of 24 studies were included, covering 5 286 patients treated with surgery alone, neoadjuvant chemotherapy (NCT), neoadjuvant radiotherapy (NRT), or neoadjuvant chemoradiotherapy (NCRT) followed by combined surgical treatment. The risk of bias of the studies was low. The results of the network meta-analysis showed that combined surgical treatments after NCRT [HR=0.77, 95%CI (0.70, 0.85)] and NCT [HR=0.89, 95%CI (0.81, 0.98)] were effective methods to improve patients' overall survival (OS) compared with surgery alone. In addition, NCRT could significantly reduce the incidence of local recurrence [OR=0.43, 95%CI (0.30, 0.58)] and distant metastasis [OR=0.71, 95%CI (0.52, 0.93)] in patients with esophageal cancer. However, NCRT [RR=1.30, 95%CI (0.77, 2.20)] increased the mortality rate of patients at 30 d after surgery. ConclusionThe available evidence suggests that NCRT combined with surgery is the best option for treating patients with resectable esophageal cancer, but this treatment carries the risk of increased 30 d postoperative mortality. Future studies should focus on optimizing the NCRT regimen with the aim of improving patients’ OS while effectively reducing postoperative mortality. In addition, more high-quality randomized controlled trials are needed to support the results of the study.
Objective To observe the effect of transcranial ultrasound stimulation (TUS) on the recovery of upper limb motor function in stroke patients and explore its mechanism. Methods The inpatients with ischemic stroke and hemiplegia admitted to the Department of Rehabilitation Medicine of the Second Affiliated Hospital of Xi’an Jiaotong University between November 2019 and December 2021were prospectively included. The patients were randomly divided into a true stimulation group and a false stimulation group. All patients received routine medication treatment and rehabilitation training, with a course of 2 weeks. The patients in the true stimulation group also received TUS, and the stimulation site and mode in the false stimulation group were the same as those in the true stimulation group, but the transducer was in a non working mode. The changes in upper limb function and motor cortex electrical activity before and after treatment were compared between two groups of patients. The Wolf Motor Function Test (WMFT), Jebsen Hand Function Test (JHFT), and Fugl-Meyer Assessment-Upper Extremities (FMA-UE) were used as indicators of upper limb motor function. The motor evoked potential (MEP) latency, resting motor threshold (RMT), cortical silent period (CSP), and central motor conduction time (CMCT) were used as indicators of cortical excitability. Results A total of 30 patients were included, with 15 in the true stimulation group and 15 in the false stimulation group. There was no statistically significant difference in age, gender, course of disease, lesion side, handedness, National Institute of Health Stroke Scale score, and Barthel Index between the two groups of patients (P>0.05). Before treatment, there was no statistically significant difference in WMFT score, JHFT time, and FMA-UE score between the two groups of patients (P>0.05). After treatment, the WMFT score and FMA-UE score of both groups of patients increased compared to before treatment within the group, while the JHFT time decreased compared to before treatment within the group (P<0.05). The improvement degree of WMFT score (19.2±8.0 vs. 11.8±5.5), JHFT time [(39.3±20.4) vs. (26.0±15.9) s], and FMA-UE score [14.0 (12.0, 16.0) vs. 8.0 (7.0, 9.0)] before and after treatment in the true stimulation group were better than those in the false stimulation group (P<0.05). Before treatment, there was no statistically significant difference in MEP latency, CSP, CMCT, and RMT between the two groups of patients (P>0.05). After treatment, the MEP latency, CSP, CMCT, and RMT of both groups of patients decreased compared to before treatment within the group (P<0.05). The degree of decrease in CSP [(33.5±12.3) vs. (18.5±5.5) ms], CMCT [3.5 (2.5, 5.8) vs. 1.8 (1.5, 3.4) ms], and RMT [(19.2±12.8)% vs. (8.8±8.7)%] in the true stimulation group before and after treatment were greater than those in the false stimulation group (P<0.05). There was no statistically significant difference in the degree of decrease in MEP latency between the two groups before and after treatment (P>0.05). Both groups of patients had no adverse reactions during the treatment period. Conclusion TUS applied to the primary motor cortex can help restore upper limb motor function in stroke patients, and the mechanism of action may be related to TUS enhancing cortical excitability in the affected brain.
The discrete choice experiment (DCE) is a stated preference analysis method used to evaluate the impact of multiple factors on individual choice, which has been explored by scholars around the world for health utility measurement. This method is considered to reduce the cognitive burden of traditional utility measurement methods and has high development potential. By examining empirical studies conducted domestically and internationally that employ DCE for measuring health utility, and drawing on methodological guidelines for constructing DCE models, this paper provides an overview of the methodological background of DCE, the practical process used for measuring health utility, and discusses relevant challenges in its application.