Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Objective: To study the effect of metformin sensitizing pancreatic cancer cells with radiotherapy, with a focus on elucidating the underlying mechanisms of radiotherapy resistance. In particular, the role of the PERK/P-eIF2/ATF4 signaling pathway in mediating these effects was preliminarily explored. Methods : Pancreatic cancer cell lines(PANC-1 and PANC-2) were categorized into control, radiotherapy, and drug treatment groups. Following the respective treatments, cell proliferation inhibition was assessed using the CCK-8 assay, colony formation assays, and cell death staining. Senescence was quantified by β-galactosidase(SA-β-Gal) staining. The expression of cell cycle regulators(P21, P16, γ-H2AX), apoptosis markers(Bax, Bcl-2, Cleaved caspase-3), and pathway-related proteins(PERK, P-eIF2, ATF4) was evaluated by Western blot and immunofluorescence. To further investigate the role of the PERK/P-eIF2/ATF4 axis in metformin-mediated modulation of pancreatic cancer cell senescence and radiosensitization, selective inhibitors(GSK2606414) and agonists(MK-28) of PERK were employed. Results : Radiotherapy markedly upregulated senescence-associated markers(P21, P16, γ-H2AX, and β-galactosidase activity) in pancreatic cancer cells. Senescent cells exhibited enhanced proliferative activity and increased tumor volume both in vitro and in vivo. Metformin mitigated radiotherapy-induced senescence by reducing the expression of senescence markers and significantly suppressing the clonogenic and proliferative capacity of treated cells. Mechanistically, radiotherapy activated the PERK signaling pathway, leading to increased expression of PERK, P-eIF2, and ATF4, thereby driving cellular senescence. Pharmacological inhibition of PERK reduced β-galactosidase activity, while PERK activation further promoted the expression of senescence-associated proteins—an effect that was reversed by metformin. Conclusion Metformin inhibits the activation of the PERK/P-eIF2/ATF4 signaling pathway in pancreatic cancer cells following radiotherapy, thereby delaying cellular senescence and reducing the associated radiotherapy resistance of senescent cells. This modulation contributes to the sensitization of pancreatic cancer cells to radiotherapy.

Objective To develop a self-care scale for patients with lymphedema after breast cancer surgery and verify its reliability and validity.Methods Based on the model of knowledge,belief and practice,a questionnaire item pool was constructed after literature reviews and qualitative interviews.A questionnaire-based scale was drafted based on the established item pool by carrying out two rounds of consultation with 15 clinical nursing specialists,nursing administrators and nursing educators from 8 provinces or cities in China.Reliability and validity of the scale were tested using convenience sampling,involving 444 patients with breast cancer surgery related lymphedema from 7 general hospitals in Hubei and Henan provinces,China,between May and July 2023.Results The response rates for the two rounds of expert consultation were 93.75%and 93.33%,respectively.The authority coefficients of the two rounds were 0.86 and 0.89,respectively,and the coordination coefficients for the 2 rounds were 0.130 and 0.379,respectively.In the first round,the average importance rating was from 4.33 to 4.93 with the coefficient of variation from 0.05 to 0.19,and the full score ratio from 53.33%to 93.33%.In the second round,the average importance rating ranged from 2.86 to 4.93 with the coefficient of variation from 0.05 to 0.36,and the full score ratios from 7.14%to 92.86%.A total of 421 patients completed the survey.The overall Cronbach's α coefficient of the scale was 0.943,the overall split-half reliability was 0.824,the scale-level content validity index(S-CVI)was 0.912,and the item-level content validity index(I-CVI)of the total scale ranged from 0.857 to 1.000.The KMO value of exploratory factor analysis was 0.919,the Bartrett spherical test value was 4671.724(P<0.001),and the cumulative variance contribution rate was 64.155%.Confirmatory factor analysis showed a good model fit.After the reliability and validity tests,the scale was finalised and determined to consist of three dimensions with 33 items:knowledge(9 items),attitude(6 items)and behaviour(18 items).Conclusion The self-care scale for the patients with lymphedema after breast cancer surgery has demonstrated good reliability and validity,and makes it an effective assessment tool for the patients with lymphedema after breast cancer surgery.

OBJECTIVES: Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of head and neck. Screening of target genes for malignant tumor therapy is one of the focuses of cancer research, with proto-oncogene and tumor suppressor gene as the breakthrough. It has become an urgent need to find the target gene related to the treatment and prognosis of LSCC.This study aims to explore the role of Lin28B and C-myc in LSCC by detecting the expressions of these two proteins and analyze the correlation between the expression of Lin28B and C-myc and clinicopathological features and prognosis of LSCC. METHODS: We detected the expression of Lin28B and C-myc proteins in 102 specimens of LSCC and 90 specimens of adjacent tissues by immunochemistry, and analyzed the correlation between Lin28B and C-myc protein expressions in LSCC as well as the correlation between the expressions of the two proteins and the clinicopathological features of LSCC. At the same time, the Kaplan-Meier method was used to analyze the relation between Lin28B and C-myc protein levels with the postoperative survival rate of LSCC patients. RESULTS: The protein levels of Lin28B and C-myc in the LSCC tissnes were significantly higher than those in the adjacent tissues (both P<0.05),and there was a positive correlation between the expression of Lin28B and C-myc in LSCC (r＝0.476, P<0.05). The expression of Lin28B protein was closely related to age, lymph node metastasis, clinical stage, tumor size, and pathological differentiation of LSCC patients (all P<0.05). while the expression of C-myc protein was closely related to lymph node metastasis, clinical stage, tumor size, and pathological differentiation of LSCC patients (all P<0.05). A relevant survival analysis showed that in patients with higher level of Lin28B (P＝0.001) or C-myc protein (P<0.001), the postoperative survival rate was relatively low. CONCLUSIONS Lin28B and C-myc proteins are highly expressed in LSCC with a positive correlation. Furthermore, they are closely related to lymph node metastasis, clinical stage, tumor size, pathological differentiation and prognosis, suggesting that both Lin28B and C-myc might be involved in the occurrence and development of LSCC.
Humans ; Squamous Cell Carcinoma of Head and Neck ; Proto-Oncogene Proteins c-myc/metabolism* ; Laryngeal Neoplasms/diagnosis* ; Carcinoma, Squamous Cell/genetics* ; Lymphatic Metastasis ; Prognosis ; Head and Neck Neoplasms ; Biomarkers, Tumor/metabolism* ; RNA-Binding Proteins/genetics*

Hepatocellular carcinoma cells interact with tumor microenvironment, and exhibits There are temporal and spatial heterogeneity of hepatocellular carcinoma which interacts with tumor microinvironment. In this paper, we summarized the characteristics of hepatocellular carcinoma heterogeneity, the mechanism of heterogeneity, and the impact of hepatocellular carcinoma heterogeneity on diagnosis and treatment, so as to provide a new thinking direction for the diagnosis and treatment of hepatocellular carcinoma.

Intestinal toxicity induced by chemotherapeutics has become an important reason for the interruption of therapy and withdrawal of approved agents. In this study, we demonstrated that chemotherapeutics-induced intestinal damage were commonly characterized by the sharp upregulation of tryptophan (Trp)-kynurenine (KYN)-kynurenic acid (KA) axis metabolism. Mechanistically, chemotherapy-induced intestinal damage triggered the formation of an interleukin-6 (IL-6)-indoleamine 2,3-dioxygenase 1 (IDO1)-aryl hydrocarbon receptor (AHR) positive feedback loop, which accelerated kynurenine pathway metabolism in gut. Besides, AHR and G protein-coupled receptor 35 (GPR35) negative feedback regulates intestinal damage and inflammation to maintain intestinal integrity and homeostasis through gradually sensing kynurenic acid level in gut and macrophage, respectively. Moreover, based on virtual screening and biological verification, vardenafil and linagliptin as GPR35 and AHR agonists respectively were discovered from 2388 approved drugs. Importantly, the results that vardenafil and linagliptin significantly alleviated chemotherapy-induced intestinal toxicity

Objective:To evaluate the effect of quantitative analysis of optical signal in the near infrared fluorescence molecular navigation surgery for oral squamous cell carcinoma (OSCC).Methods:SCC9, HSC3 and epithelial cell lines (Leuk-1) were co-cultured with indocyanine green (ICG) for 6 hours in vitro in order to verify whether the quantitative analysis of near infrared optical signal could distinguish tumor cells from normal cells. A total of 16 BALB/c male mice (5-6 weeks, 20-25 g) were selected and fed in clean grade equipment and were equally divided into two groups. SCC9 and HSC3 cells were inoculated into the back of each mouse at a concentration of 1×10 6 cells/ml to establish a subcutaneous graft tumor model. The 5 mg/kg ICG was injected into the caudal vein to each of the tumor bearing mouse and the difference between OSCC and normal tissues was then analyzed by near infrared optical signal quantitative analysis (Paired t test). Ten patients with OSCC were enrolled in the Department of Stomatology of the First Affiliated Hospital of Bengbu Medical College from November 2019 to July 2020, including 6 patients with tongue squamous cell carcinoma and 4 patients with buccal squamous cell carcinoma.The patients were 6 males and 4 females and the range of age was from 46 to 71 years with an average age of 58.6 years. These patients were injected ICG (0.75 mg/kg) via the cubital vein at 6-8 h before surgery. Intraoperatively, the fluorescence intensities (FI) of near infrared signal were measured at tumor, peritumor tissues (2.0 cm beyond the tumor boundary) and normal tongue or buccal mucosa respectively. The signal background ratios (SBR) from the three site groups were assessed using one-way ANOVA followed by the Tukey post hoc test for multiple comparisons. Results:In vitro, the levels of near infrared FI in HSC3 and SCC9 groups were higher than that in Leuk-1group ( P<0.01). In vivo, the result showed that the SBR of OSCC and normal tissues was 8.67±0.35. Clinical studies showed that the intensity of tumor [(408.23±101.51) arbitrary units (AU)] was significantly higher than those of peritumoral [(253.12±64.89) AU] and normal tissues [(261.50±80.47) AU] respectively. The SBRs of near infrared FI of tumor and peritumoral tissues, tumor and normal tissues were 1.61±0.53 and 1.56±0.48 respectively, while that of peritumoral and normal tissues was 0.96±0.17. Conclusions:The quantitative analysis of near infrared optical signal could distinguish OSCC from normal cells and could locate the OSCC tissue intraoperatively. Optical signal quantification and ICG near infrared fluorescence molecular technology possessed the feasibility in primary OSCC resection.

Neurotransmitters play an important role in nervous system. Temporal and spatial changes of neurotransmitter distribution are crucial to information processing in neural networks. Biosensors that can visually monitor neurotransmitters are one of the vital tools to explore a variety of physiological and pathological activities. This article reviews recent advances in monitoring neurotransmitters with high temporal and spatial resolution, and introduces the latest fluorescent imaging methods for typical neurotransmitters, including glutamate, dopamine, γ-aminobutyric acid and acetylcholine. The article also summarizes the basic principles, advantages and disadvantages of various visually detection methods, and provides systematic suggestions for designing neurotransmitter sensors with high temporal and spatial resolution.
Animals ; Biosensing Techniques ; instrumentation ; trends ; Fluorescence ; Humans ; Neurotransmitter Agents ; metabolism

Objective To evaluate the effectiveness and safety of double balloon enteroscopy( DBE) in retrieval of retained capsule and identify the factors associated with successful retrieval. Methods A total of 23 consecutive retention cases who received retrieval of retained capsules by DBE from January 2010 to December 2013 were reviewed. They were assigned to success group and failure group. The differences in insertion route, insertion depth, lesion location between the two groups were analyzed. Results Fifteen cases of all 23 retention cases were successfully retrieved and the success rate was 65?2%. There was no significant difference in the mean entrapped period of CE between the two groups [20?0(15?0,57?0)d VS 21?0(16?0,240?0) d,P=0?525]. DBE via oral route exhibited remarkable higher success rate than anal route [ 71?4%( 15/21) VS 0/5, P=0?007] . Compared with ileum, it was easier to take out CE located at jejunum( 8/8 VS 7/13, P=0?046 ) and the insertion depth was significantly less in the success group [(167?3±33?8)cm VS (258?3±23?9) cm, P=0?041]. Whether the capsule was in pelvic cavity shown by x?ray film before the surgery was irrelevant to the successful rate(9/14 VS 5/6,P=0?613) and insertion depth of the DBE on access to the capsule[(132?0±68?6) cm VS (200?0±40?3) cm, P=0?376],or to the actual location of the capsule. Conclusion Peroral DBE is an effective method for removal of retained CE and the success rate isn′t relevant to the entrapped period. Retained CE locates in ileum and jejunum is more difficult to be taken out than in duodenum.

Objective To understand the correlation between operating room nurses′cognition of patient safety culture and hospitals responsibility,so as to provide basis to establish patient safety measures. Methods A total of 98 operating room nurses participating the meeting were investigated by convenience sampling method with Nurse′s Organizational Climate Scale and Patient Safety Culture Assessment Scale. Results The mean score of nurses′ cognition of patient safety culture was 3.58 ± 0.30,which showed a high level. The mean score of operating room nurses′perception of psychological contract was 2.17 ± 0.58,which was below the middle level. There was a negative correlation between nurses′cognition of patient safety culture and psychological contract (P<0.05). Conclusions Hospitals responsibility need to improve urgently. Nursing administrators should improve resource guarantee, management support and team behavior,in order to promote positive nurses′consciousness and behavior of patient safety and ensure the safety of patients .