Protein liquid-liquid phase separation (LLPS), a pivotal phenomenon intricately linked to cellular processes, is regulated by various other proteins. However, there is still a lack of high-throughput methods for screening protein regulators of LLPS in target proteins. Here, we developed a CRISPR/Cas9-based screening method to identify protein phase separation regulators by integrating bimolecular fluorescence complementation (BiFC) and fluorescence-activated cell sorting (FACS). Using this newly developed method, we screened the RNA-binding proteins that regulate PABPN1 phase separation and identified the tumor suppressor QKI as a promoter of PABPN1 phase separation. Furthermore, QKI exhibits decreased expression levels and diminished nuclear localization in colorectal cancer cells, resulting in reduced PABPN1 phase separation, which, in turn, promotes alternative polyadenylation (APA), cell proliferation, and migration in colorectal cancer.
Humans ; Colorectal Neoplasms/genetics* ; RNA-Binding Proteins/genetics* ; Poly(A)-Binding Protein I/genetics* ; CRISPR-Cas Systems ; Flow Cytometry ; Cell Proliferation ; Cell Line, Tumor ; Cell Movement

Sarcopenia, which is characterized by progressive and generalized loss of skeletal muscle mass and strength, has been well described to be associated with numerous poor postoperative outcomes, such as increased perioperative mortality, postoperative sepsis, prolonged length of stay, increased cost of care, decreased functional outcome, and poorer oncological outcomes in cancer surgery. Multimodal prehabilitation, as a concept that involves boosting and optimizing the preoperative condition of a patient prior to the upcoming stressors of a surgical procedure, has the purported benefits of reversing the effects of sarcopenia, shortening hospitalization, improving the rate of return to bowel activity, reducing the costs of hospitalization, and improving quality of life. This review aims to present the current literature surrounding the concept of sarcopenia, its implications pertaining to colorectal cancer and surgery, a summary of studied multimodal prehabilitation interventions, and potential future advances in the management of sarcopenia.

Objective     To summarize the progress and trend on clinical drug trials of esophageal squamous cell carcinoma in China. Methods     Based on the clinical drug trial registration and information disclosure platform and the drug data query system of the National Medical Products Administration, the characteristics of clinical trials, investigational drugs and listed drugs of esophageal squamous cell carcinoma in China from 2012 to 2021 were analyzed. Results     From 2012 to 2021, a total of 49 clinical drug trials of esophageal squamous cell carcinoma were registered in China, accounting for 1.6% of all clinical trials of anticancer drugs. Among them, there were 39 (79.6%) trials initiated by domestic pharmaceutical enterprises, 6 (12.2%) for adjuvant and neoadjuvant treatment, and 9 (18.4%) for local treatment. There were differences in the treatment line distribution between global and domestic enterprise-initiated trials (P=0.032). The above trials covered 29 investigational drugs, including 23 (79.3%) targeted drugs, most of which targeted programmed death-1, programmed death-ligand 1 and epidermal growth factor receptor. From 2012 to 2021, there were 2 drugs for esophageal squamous cell carcinoma listed in China, both of which were approved for the first-line and second-line treatment. Conclusion     Great achievements have been made in the clinical development of esophageal squamous cell carcinoma drugs in China. It is suggested that domestic enterprises increase the investment of esophageal squamous cell carcinoma, pay attention to adjuvant and local treatment, explore novel targets and drug categories, and focus on the details of pivotal trials.

Group psychological counseling techniques commonly used in nurses' mental health promotion include mindfulness-based group counseling, Balint groups, psychodrama, and the Satir model. Group psychological counseling mainly promotes the mental health of nurses by decreasing nurses' stress, relieving negative emotions, reducing job burnout, enhancing the perceived professional benefit, improving interpersonal relationships and adaptability. This paper reviews the common techniques and application of group psychological counseling, and analyzes the advantages and challenges of group psychological counseling in the promotion of nurses' mental health, with a view to providing a reference for the research and practice of nurses' mental health promotion based on group psychological counseling for researchers.

Group psychological counseling techniques commonly used in nurses' mental health promotion include mindfulness-based group counseling, Balint groups, psychodrama, and the Satir model. Group psychological counseling mainly promotes the mental health of nurses by decreasing nurses' stress, relieving negative emotions, reducing job burnout, enhancing the perceived professional benefit, improving interpersonal relationships and adaptability. This paper reviews the common techniques and application of group psychological counseling, and analyzes the advantages and challenges of group psychological counseling in the promotion of nurses' mental health, with a view to providing a reference for the research and practice of nurses' mental health promotion based on group psychological counseling for researchers.

Objective: To investigate the effect of a metal occlusal surface and stress interruption design on minimally invasive prosthodontics for patients with distal extension absence and insufficient occlusal gingival distance. Methods : We retrospectively studied the case of minimally invasive prosthodontic (Vitallium 2000) combined with a metal occlusal surface for distal extension absence in a patient with insufficient occlusal gingival distance; the stress breaking design and pressure impression technology are examined, and relevant articles are reviewd. Results: The design effectively solves the problems of insufficient occlusal gingival distance, large occlusal force and easy denture fracture. Reviewing the relevant literature, stress interruption design can effectively protect abutment teeth, but the behavior of stress interruption design and stress conduction phenomena in the mouths of patients has not been reported. The T-scan test results of this study showed that before and after wearing the denture, the occlusal force distribution ratio of the patient changed from 77.5% on the left and 22.5% on the right to 61.3% on the left and 38.7% on the right. The occlusal force distribution ratio of the right dentition to the total occlusal force increased by 16.2%, and the occlusal force became better distributed. Further analysis showed that the occlusal forces on the left and right sides were nearly the same in the initial occlusion stage. As the occlusal force was further increased, the proportion of the occlusal force on the right side decreased in the middle of the occlusion stage and further decreased in the final occlusion stage until it reached a dynamic balance. The above T-scan test and literature review results suggest that this dynamic balance phenomenon of bite force is related to the stress interruption design and the stress conduction effect of the split framework. Conclusion The composite of stress interruption design and metal occlusal surface allows for minimally invasive prosthodontics for the treatment of distal extension absence in patients with insufficient occlusal gingival distance.

Objective To investigate the feasibility of the highGresolution MRI (HRGMRI)in diagnosing the intracranial artery dissection (IAD)and to improve radiological diagnostic accuracy in clinical practice.Methods The clinical data and imaging data of 43 patients with suspected IAD were analyzed retrospectively.HRGMRI and DSA examinations were performed.HRGMRI images were reviewed by two experienced radiologists independently,and DSA images were analyzed by a neurosurgeon.FollowGup durations were from 3 months up to 12 months,and then the clinical diagnoses of IAD were made.The sensitivity,specificity,positive predictive value (PPV),and negative predictive value (NPV)of HRGMRI were calculated,and the consistency of HRGMRI and DSA in the diagnosis of IAD was made.Results 32 over 43 patients were detected to be positive by HRGMRI,however,34 of 43 patients were diagnosed as IAD clinically.The sensitivity and specificity of HRGMRI for detecting IAD were 9 1.2% and 88.9%,respectively.The PPV was 96.9%,and the NPV was 72.7%.For DSA,30 patients with IAD were detected and 1 3 patients had negative results.Compared with the HRGMRI (3 2/43),the coincidence rate of two examinations was 86.0%.McNemer test (P＝0.687)indicated that there was no significant difference between two methods.Conclusion HRGMRI has excellent soft tissue contrast and spatial resolution.As a nonGinvasive modality with good tissue contrast and spatial resolution,it plays an important role in the diagnosis,differential diagnosis and followGup of IAD.

磷脂酰肌醇蛋白聚糖3(glypican-3，GPC3)是一种锚定在细胞膜上的硫酸乙酰肝素(heparan sulfate，HS)蛋白多糖的家族成 员之一。GPC3激活经典的Wnt/β-连环蛋白(β-catenin)途径在肝癌(hepatocellular carcinoma，HCC)中表现出促癌基因的作用。尽 管GPC3在胎肝中含量丰富，在多种实体肿瘤中高表达，然而在成人正常组织中含量极少。选择靶点是肿瘤免疫治疗的关键。迄 今为止靶向GPC3的MRI、PET和近红外成像已被用于早期HCC检测。针对GPC3+实体瘤也已经开发了各种免疫治疗方案，一种 是基于抗GPC3抗体包括单克隆抗体、多肽疫苗、免疫毒素、双特异性抗体等，一种是靶向GPC3的CAR-T/NK疗法，其中部分已 进入I/II期临床试验。靶向GPC3有可能为实体瘤治疗提供新的工具。本文概述GPC3的结构、功能等生物学特性，介绍基于抗 GPC3抗体、CAR-T细胞开发的新策略，提供GPC3免疫疗法靶向实体瘤的证据。

Objective: To investigate the expression of IFIT2 (interferon-induced protein with tetratricopeptide repeats 2) in human lung cancer tissue and analyze the relationship between the IFIT2 expression and clinicopathological features and prognosis. Methods: Tissue microarray and immunofluorescence staining were used to examine the IFIT2 expression in lung cancer tissue and their adjacent tissues. Wilcoxon rank test was used to compare the IFIT2 expression in lung cancer and corresponding adjacent tissues. The chi-square test was used to analyze the relationship between the IFIT2 expression in lung cancer tissues and clinicopathological features of the patients. Kaplan-Meier survival analysis was performed to analyze the correlation between IFIT2 expression and patients′ overall survival. Cox model was used to analyze the correlation between different clinical parameters and prognosis. Results: There was significant difference for the IFIT2 expression between the lung cancer tissues and adjacent tissues (P＜0.01). There was no significant correlation between IFIT2 expression and clinicopathological features of patients (P＞0.05). In lung adenocarcinoma and squamous cell carcinoma, Kaplan-Merier survival analysis showed that the overall survival (OS) of patients in IFIT2 low expression group was significantly shorter than that in IFIT2 high expression group (HR=2.392, 95%CI: 1.103-5.186, P=0.027; HR=2.907, 95%CI: 1.118-7.559, P=0.029, respectively). Multi-factor Cox model analysis indicated that distant metastasis (HR=8.033, 95% CI: 3.664-17.614, P=0.000) was independent prognostic factors for lung adenocarcinoma, lymph node metastasis (HR=3.390, 95% CI: 1.029-11.175, P=0.045) and IFIT2 low expression (HR=3.762,95%CI: 1.236-11.451, P=0.020) were independent prognostic factors for lung squamous cell carcinoma. Conclusion The down-regulated expression of IFIT2 in lung cancer tissues suggests that it may play an important role in initiation and development of lung cancer. It could be used as a valuable risk factor to predict the prognosis of lung cancer patients.

Objective: To investigate the effect of IFN-γ on the expression of IL-33 in colon cancer CT26 cells. Methods: CT26 cells were treated with IFN-γ and IFN-γ combined with PKA inhibitor H89, respectively, and a negative control group (NC, untreated) was set up at the same time. The mRNA expression levels of PKA, CREB and IL-33 in CT26 cells were detected by qRT-PCR. The expression levels of PKA, CREB, p-CREB and IL-33 proteins in CT26 cells were determined by western blot. The localization of CREB protein in CT26 cells was analyzed by the immunofluorescence confocal microscopy. Results: The relative expression levels of PKA, CREB and IL-33 mRNA in the IFN-γ-treated group were 2.50±0.11, 3.10±0.08 and 2.80±0.22, respectively, which were significantly higher than those in the NC group (P＜0.05). The relative expression levels of PKA, CREB and IL-33 mRNA in the IFN-γ combined with H89 treatment group were 0.21±0.02, 0.59±0.05 and 0.35±0.04, respectively, which were significantly lower than those in the NC group and IFN-γ-treated group (P＜0.05). The expression levels of PKA, CREB and IL-33 proteins detected by western blot were consistent with that of mRNA. Immunofluorescence confocal results showed that the expression level of CREB in the IFN-γ-treated group was significantly higher than that in the NC group, and that the expression level of CREB in the IFN-γ combined with H89 treatment group was significantly lower than that in the IFN-γ-treated group. Conclusion IFN-γ may induce the expression of IL-33 in colon cancer CT26 cells via the PKA-CREB pathway.