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 establish a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for accurate determination of plasma Lyso-GL-3 concentration.Method:Solid phase extraction technology was used to process plasma samples, and under positive ion mode and multiple reaction monitoring (MRM) conditions, LC-MS/MS was used to determine the concentration of Lyso-GL-3. The linear range, detection and quantification limits, accuracy, precision, matrix effect, carrier effect of the method, and plasma sample stability were validated. And the accuracy of Lyso-GL-3 positive patients was compared by combining enzymatic and genetic testing results.Result:Lyso-GL-3 had good linearity in the range of 1.25-400 nmol/L. The detection limit and quantification limit were 0.15 nmol/L and 0.50 nmol/L, respectively. The spiked recovery rate was 88.78%-108.96%. The coefficient of variation ( CV) for intra batch precision, inter batch precision, and matrix effect were all less than 15%, the result of carrier effect was 0.55%. Plasma samples could be stably stored for 30 days under refrigeration conditions. The clinical conformity of the patient was 100%. Conclusion:The established LC-MS/MS detection method for plasma Lyso-GL-3 concentration takes 2.5 minutes, which is simple, fast, accurate, and reliable.

Objective To explore the relationship between systemic immune-inflammation index(SII),red blood cell distribution width(RDW),25-hydroxy-vitamin-D[25(OH)D]levels and frailty index in elderly pa-tients with type 2 diabetes mellitus(T2DM).Methods A total of 197 elderly patients with T2DM admitted to the hospital from March 2023 to March 2024 were collected as the research subjects.The patients were divided into the frailty group(106 cases)and the non-frailty group(91 cases)according to the scores of the clinical frailty scale.The clinical data and the levels of SII,RDW and 25(OH)D of the two groups were compared.Pearson correlation analysis was used to analyze the correlations between the levels of SII,RDW and 25(OH)D and the frailty index of elderly patients with T2DM.Logistic regression was used to analyze the influencing factors of frailty in elderly patients with T2DM.Results Compared with the non-frailty group,the proportion of women,the history of falls within 1 year,and the age of the frailty group increased,while the body mass in-dex and the proportion of men decreased,and the differences were statistically significant(P＜0.05).The SII and RDW levels in the non-frailty group were lower than those in the frailty group,and the 25(OH)D level was higher than that in the frailty group,and the differences were statistically significant(P＜0.05).Pearson correlation analysis showed that SII and RDW levels were positively correlated with frailty index,and 25(OH)D level was negatively correlated with frailty index in elderly T2DM patients(P＜0.05).Logistic regression analysis showed that female,age ≥ 74.25 years old,SII≥ 938.36,RDW≥ 15.19％,and 25(OH)D≥48.42 nmol/L were independent risk factors for frailty in elderly T2DM patients(P＜0.05).Conclusion The levels of SII,RDW and 25(OH)D in elderly patients with T2DM are related to the frailty index.

Müller cells(MCs)are the most common glial cells in the human retina. They provide homeostatic, metabolic, and functional support to neurons. MCs play a critical role in regulating extracellular space volume, ion and water homeostasis, and maintaining the blood-retinal barrier. They release gliotransmitters and other neuroactive molecules, influencing synaptic activity through neurotransmitter recycling. All these functions directly or indirectly alter neuronal activity. MCs support the survival of photoreceptors and neurons, are responsible for the structural stability of the retina, and act as regulators of immune and inflammatory responses. They are activated in response to almost all pathogenic stimuli. Reactive MCs have neuroprotective effects, but excessive activation of MCs under pathological conditions can withdraw neuronal protection and lead to neuronal degeneration. Thus, MCs may play a double-edged sword role in the pathogenesis of macular edema due to retinal vein occlusion(RVO-ME). Understanding the response of MCs to pathological stimuli and their protective and damaging effects on the retina and macula is crucial for studying the pathogenesis and guiding the treatment of RVO-ME. This article reviews the role of MCs in RVO-ME, aiming to provide new strategies for the treatment of RVO-ME.

Objective:To establish a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for accurate determination of plasma Lyso-GL-3 concentration.Method:Solid phase extraction technology was used to process plasma samples, and under positive ion mode and multiple reaction monitoring (MRM) conditions, LC-MS/MS was used to determine the concentration of Lyso-GL-3. The linear range, detection and quantification limits, accuracy, precision, matrix effect, carrier effect of the method, and plasma sample stability were validated. And the accuracy of Lyso-GL-3 positive patients was compared by combining enzymatic and genetic testing results.Result:Lyso-GL-3 had good linearity in the range of 1.25-400 nmol/L. The detection limit and quantification limit were 0.15 nmol/L and 0.50 nmol/L, respectively. The spiked recovery rate was 88.78%-108.96%. The coefficient of variation ( CV) for intra batch precision, inter batch precision, and matrix effect were all less than 15%, the result of carrier effect was 0.55%. Plasma samples could be stably stored for 30 days under refrigeration conditions. The clinical conformity of the patient was 100%. Conclusion:The established LC-MS/MS detection method for plasma Lyso-GL-3 concentration takes 2.5 minutes, which is simple, fast, accurate, and reliable.

OBJECTIVE To evaluate the impact of the specialized centralized procurement policy for insulin on daily cost and affordability of insulin,and provide data support for the enhancement of relevant policies.METHODS In this research,the insulin purchasing data were obtained from provincial centralized procurement platforms in provinces before and after the specialized centralized procurement of insulin(October-December 2021 and October-December 2022),and the cost variations of insulin before and after the centralized procurement were analyzed by the defined daily dose cost(DDDc)of various types of insulins.The changes in the affordability of various types of insulins before and after the specialized centralized procurement were evaluated,using the percentage of annual expenditure on various types of insulins relative to annual per capita disposable income(i.e.the proportion of annual expenditure)as an indicator.RESULTS After the specialized centralized procurement,DDDc of various types of insulins decreased by 20.7%-71.8%,with an average reduction of 45.7%.Moreover,the reduction in DDDc for third-generation insulin exceeded that for second-generation insulin.The reduction in the proportion of annual expenditure on insulin ranged from 24.3%to 73.4%,with an average decrease of 48.5%.Premixed insulin analogs experienced the greatest reduction(73.4%).Following the specialized centralized procurement,DDDc of insulin decreased in all provinces.Except for Guangxi(10.2%),the average proportion of annual expenditure on insulin in the remaining provinces dropped to below 10%.CONCLUSIONS The specialized centralized procurement policy for insulin has significantly reduced insulin costs and improved affordability,thereby alleviating the economic pressure on patients with diabetes.There are notable cost disparities among provinces and among insulin categories,which require attention.

Objective To analyze the changes of relaxation values of different brain gray matter nuclei in patients with Parkinson's disease(PD)by synthetic magnetic resonance imaging(SyMRI),and to explore the correlation between relaxation values and clinical subtypes of PD,so as to provide some imaging basis for the diagnosis and classification of PD.Methods A total of 53 patients with PD and 34 healthy controls(HC)were scanned by SyMRI sequence.The patients with PD were divided into early group(33 cases),middle and late group(20 cases),postural instability/gait difficulty(PIGD)group and tremor dominant(TD)group.The region of interest(ROI)was drawn manually and the T1,T2 and proton density(PrD)values of different brain gray matter nuclei were measured,respectively.The differences between the groups were compared.Results There were statistical differences between the PD group and the HC group in multiple gray matter nuclei and multiple relaxation value parameters(P＜0.05).There were statistical differences in the relaxation values of gray matter nuclei such as head of the caudate nucleus,body of the caudate nucleus,putamen,globus pallidus,thalamus,red nucleus,and substantia nigra among the early PD group,the middle and late PD group,and the HC group,and red nucleus PrD value had the most testing effectiveness in the diagnosis of early PD[area under the curve(AUC)0.823,P＜0.001].There were statistical differences in the relaxation values of gray matter nuclei such as head of the caudate nucleus,putamen,and thalamus between the PIGD group and the TD group(P＜0.05).Conclusion It is found that there are statistical differences in different nuclear relaxation values between PD patients and healthy people,as well as between PD patients with different clinical types via SyMRI,suggesting that SyMRI has a certain clinical value in the diagnosis and classification of PD.

Objective To explore the relationship between serum lipoprotein(a),Apelin-13,and transforming growth factor beta 1(TGF-β1)and left atrial diameter(LAD)in patients with atrial fibrillation(AF).Methods A total of 100 patients who were admitted to Chuzhou First People's Hospital between December 2022 and January 2024 were selected as research objects.There were 50 patients with AF(AF group)and 50 patients without AF(NAF group).Serum levels of lipoprotein(a),Apelin-13,and TGF-β1 were detected,and LAD were measured by transthoracic echocardiography.Results Compared with those in the NAF group,lipoprotein(a),TGF-β1 and LAD were increased significantly in the AF group,while Apelin-13 was decreased significantly(P<0.05).Multivariable logistic regression revealed that lipoprotein(a),TGF-β1,diastolic blood pressure and LAD were risk factors of AF,while Apelin-13 was a protective factor of AF(P<0.05).Furthermore,lipoprotein(a),TGF-β1,LAD and Apelin-13 had predictive value for AF(P<0.05).Linear regression results showed that the coefficients of lipoprotein(a),TGF-β1 and Apelin-13 influencing on LAD were 0.01(P>0.05),-0.04(P>0.05)and-1.22(P<0.05),respectively.Conclusion Lipoprotein(a),TGF-β1 and LAD are independent risk factors of AF.However,lipoprotein(a)and TGF-β1 have no notable relation with LAD.As an independent protective factor of AF,Apelin-13 is significantly negatively correlated with LAD.

The"season-visceral-related"theory originated from Huangdi Neijing,and its content contains the"holism of five viscera"and"correspondence between nature and humans"in the theoretical system of traditional Chinese medicine(TCM).Recently,the prevalence of post-stroke cognitive impairment(PSCI)has gradually increased with the increasing incidence of stroke.TCM believes that PSCI is located in the brain,however,the causative factors such as phlegm,depression,deficiency,and stasis are caused by the lesions of the five zang viscera.Therefore,PSCI can not be treated with the brain alone.Based on the"season-visceral-related"theory,this article discusses the etiology,pathogenesis,and treatment ideas for PSCI from the four seasons and five zang viscera.Xiaoyao Pill was selected as a treatment for patients with qi imbalance in spring to disperse stagnated liver qi to relieve qi stagnation.Tianwang Buxin Dan was selected as a treatment for patients with blood loss and spirit injury in the summer to nourish the blood and calm the heart and brain.Kaixin Powder was selected as a treatment for patients with spleen deficiency and phlegm blockage in late summer to strengthen the spleen,awaken the mind,and remove stasis.Wenfei Jiangzhuo Decoction was selected as a treatment for patients with qi deficiency and spirit departure in autumn to nourish the lungs,reduce turbidity,and nourish the mind.Dihuang Yinzi was selected as a treatment for patients with marrow reduction and internal toxin in winter to expel phlegm and fill the mind.Treating PSCI using the"season-visceral-related"theory reflects the overall concept of TCM and the hypothesis of syndrome differentiation and treatment and provides novel method for treating PSCI.