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

Dyslipidemia is an important risk factor of atherosclerotic cardiovascular disease (ASCVD). Statins delay the occurrence and development of ASCVD, and reduce the risk of cardiovascular events and death. Due to safety concerns, there exist insufficient use of lipid-lowering agents and a high withdrawal rate of the agents in the elderly. To promote the prevention and treatment of ASCVD, this expert consensus is issued and focuses on the management of dyslipidemia of Chinese elderly basing on the clinical evidence of the use of lipid-lowering drugs by the elderly, and the lipid management guidelines and expert consensus recommendations at home and abroad.

Carcinoma, Non-Small-Cell Lung ; classification ; therapy ; China ; Humans ; Lung Neoplasms ; classification ; therapy ; Practice Guidelines as Topic ; Receptor Protein-Tyrosine Kinases ; metabolism

Objective To observe the short-term efficacy and safety of sequential administration of erlotinib and chemotherapy in unselected, chemonaive patients with advanced non-small-cell lung cancer (NSCLC). Methods Previously-untreated patients (n=23) with stage Ⅲ_B/Ⅳ NSCLC and ECOG PS of 0/1 received erlotinib (150 mg/d) on days 15-28 of a 4-week cycle that included gemcitabine (1250 mg/m~2, days 1 and 8), and either cisplatin (75 mg/m~2, day 1) or carboplatin (AUC=5, day 1). The primary end points were tumor response rate and safety. Results 23 patients received a total of 95 cycles of treatment, and all were evaluable for efficacy and toxicity. The overall response rate was 30.4%, 0 case achieved complete responses (CR), 7 cases (30.4%) achieved partial responses (PR), 14 cases (60.9 %) achieved stable disease (SD), 2 cases (8.7 %) achieved progression disease (PD). The disease control rate was 91.3 %. The sequential administration of erlotinib following gemcitabine/platinum chemotherapy was well tolerated. The major grade 3 treatment-related adverse events were eutropenia (13.4%), rash (8.7%), nausea (8.7%) and thrombocytopenia (8.7%). No treatment-related interstitial lung disease. Conclusion equential administration of erlotinib following gemcitabine/platinum chemotherapy was effective, and the toxicity was tolerable. This treatment strategy warrants further investigation.

For advanced lung cancer,multimodality treatment is the main stream.Patients with locally advanced disease may have long-term survival rate with radiation therapy combined with chemotherapy.Patients with advanced metastatic disease may achieve improved survival and palliation of symptoms with chemotherapy.Here we reviewed the recent development in treatment for advanced non-small cell lung cancer.

BACKGROUNDDendritic cell (DC)-based immunotherapy is a new approach and effective for some malignant tumors. The aim of this study is to observe the efficacy and toxicity of immunotherapy with carcinoembryonic antigen (CEA) peptide-pulsed DCs in patients with refractory advanced lung cancer.

METHODSLung cancer patients with high CEA expression were enrolled into this project. Autologous DCs were generated from patients' plastic-adherent peripheral blood mononuclear cells and loaded with CEA 5 days later. Cytokine-induced killer cells (CIK) were cultured from non-adherent peripheral blood mononuclear cells. DCs and CIK were transfused to patients. Responses and toxicities were observed.

RESULTSA total of 22 patients with lung cancer received DCs immunotherapy. DCs doses were 2.5×10⁶-9.6×10⁷ (5.03×10⁶). CIK doses were 3.4×10⁸-46×10⁸. CD3, CD8, NK and IFN-γ levels obviously increased after treatment (P < 0.05). The 1-year survival rate was 68.2% (15/22). Main toxicities were fever and rash.

CONCLUSIONSDCs-based immunotherapy is feasible and safe to patients with lung cancer.

BACKGROUNDTo compare the effect and toxicity between gemcitabine and cisplatin (GP) with vinorelbine, ifosfamide and cisplatin (NIP) combined chemotherapy in the treatment of patients with advanced non-small cell lung cancer (NSCLC).

METHODSEighty patients received either gemcitabine 1 000 mg/m² on days 1, 8, or 15 plus cisplatin 70-80 mg/m² on day 1, or vinorelbine 25 mg/m² on days 1, 8, ifosfamide 1.2 g/m² on days 1-4 plus cisplatin 70-80 mg/m² on day 1, every 28 days as a cycle.

RESULTSThe objective response rate was 40.0% in GP goup, compared with 52.5% in NIP group (P > 0.05). Median survival time of GP and NIP groups was 13.68 and 15.34 months respectively, and 1-year survival rates were 54.29% and 59.46% respectively (P > 0.05). Leukopenia at grade III+IV was significantly lower in GP arm (27.5%) than that in NIP arm (55.0%) (P < 0.05). Non-hematological toxicities were less frequent in GP group than those in NIP group (P < 0.05).

CONCLUSIONSAlthough the response rate tends to be higher in three-drug than in two-drug combined chemotherapy, but no significant difference is observed. Three-drug combinations often result in more toxicities. Two-drug combination GP may be the standard protocol for chemotherapy of advanced NSCLC. Three-drug combination NIP should be given to young patients with good performance status.

The clinical evidences of the guideline came from clinical trials based evidence-based medicine. Applied principle of the evidence was: systematic reviews, RCTs, the results from multiple factors ana-lysis, consensus, especially combined with Chinese experience and some lung cancer guidelines used in USA or Europe. All doctors who use the guideline in making therapeutic strategy must combine patients' conditions with the knowledge of biological behavior, dynamic change and response to treatment of lung cancer.