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

ObjectiveTo analyze the detected results of CD4⁺T lymphocytes and viral load in newly identified human immunodeficiency virus (HIV) infected patients in Huangpu District of Shanghai in 2023, to explore the correlation between them, so as to provide a scientific basis for the development of targeted prevention and control measures and antiviral treatment programs. MethodsThe data of CD4 cell count, viral load and demographic characteristics of the newly infected patients living with HIV in Huangpu District, Shanghai in 2023 were collected and analyzed by using descriptive epidemiological method. ResultsThe mean CD4 cell count of the 67 newly identified HIV infected patients in Huangpu District was (301.22±235.19) cells·µL^-1, with a mean viral load of (5.15±1.28) ×10⁵ copies·mL^-1.There were statistically significant differences in CD4 cell count and viral load among different age groups (P<0.05), but there were no statistically significant differences by gender and marital status (both P>0.05). The CD4 cell count and CD4/CD8 ratio both were negatively correlated with the lg value of viral load (r=-0.290, -0.378; P=0.027, 0.002). ConclusionThe CD4 cell counts of the newly identified HIV infected patients in Huangpu District in 2023 were generally low, the proportion of patients with high viral load was high, but the risk for elderly infected with HIV was high. The elderly have gradually become the key population for AIDS prevention and control in Huangpu District. It is recommended to expand HIV screening in the elderly to reduce the risk of HIV transmission and increase the rate of early detection and treatment.

Objective To analyze the CT imaging features of renal parenchymal urothelial carcinoma and other renal infiltrative lesions,and to improve the diagnostic and differential diagnostic accuracy of renal parenchymal urothelial carcinoma.Methods The clinical and imaging data from 60 patients with renal infiltrative lesions involving both the renal pelvis and renal parenchyma confirmed by pathology were collected,including 27 cases of renal parenchymal urothelial carcinoma,20 cases of renal papillary cell carcinoma,and 13 cases of renal lymphoma.All patients underwent plain and three-phase enhanced scans.Clinical manifestations and imaging fea-tures were analyzed,and the tumor/cortex CT ratio was measured on plain and three-phase enhanced scans,and statistically ana-lyzed.Results The renal contour of some patients with renal papillary cell carcinoma was altered and locally protruded beyond the contour,while the remaining patients had a normal renal morphology,with involvement of either a renal segment or the entire kid-ney,and unclear cortex-medulla differentiation.All three types of tumors showed mild to moderate progressive enhancement.The tumor/cortex CT ratio on plain scan had no statistical significance among the three groups(P＞0.05),while the tumor/cortex CT ratio on three-phase enhanced scan showed statistical significance(P＜0.05).Conclusion There are differences in imaging manifes-tations between renal parenchymal urothelial carcinoma and other renal infiltrative lesions,with significant differences in the phase of peak enhancement.

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 analyze the morphological alterations of corpus callosum in children with spastic cerebral palsy(SCP)using three-dimensional magnetization prepared rapid acquisition gradient echo(3D-MPRAGE)technology and to investigate the correlation between morphological indexes and gross motor function.Methods Sagittal T1WI 3D-MPRAGE data was collected from 136 children with SCP(SCP group)and 132 age-and gender-matched healthy controls(HC)(HC group),and the gross motor function measure-88(GMFM-88)was applied to assess the gross motor function.Independent sample t-test was used to compare the corpus callosum surface area,volume,maximum anterior-posterior diameter,median sagittal area(total area and area of Ⅰ-Ⅴ zone)between the two groups.Partial correlation analysis was performed to calculate the correlation between morphological indexes of the corpus callosum and GMFM-88 with age as a covariate.Results Children under 3 years old,the corpus callosum surface area of the SCP group(3 914.51 mm2±1 207.97 mm2)was lower than that of the HC group(5 725.51 mm2±1 412.66 mm2).The volume of the corpus callosum(6 108.46 mm3±2 803.97 mm3)in the SCP group was lower than that of the HC group(11 297.96 mm3±4 109.02 mm3).Also,the maximum anterior-posterior diameter of the corpus callosum in the SCP group(53.40 mm±6.31 mm)was lower than that of the HC group(57.74 mm±6.04 mm)(all P<0.05).Children over 3 years old,the corpus callosum surface area of the SCP group(4 970.06 mm2±1 191.31 mm2)was lower than that of the HC group(6 372.55 mm2±1 445.59 mm2).The volume of the corpus callosum(8 330.20 mm3±2 888.20 mm3)in the SCP group was lower than that of the HC group(13 599.82 mm3±3 429.81 mm3)(all P<0.05).Partial correlation analysis showed significant correlation between corpus callosum volume,median sagittal area and gross motor score(P<0.01)with age as a covari-ate.Conclusion The 3D-MPRAGE technology can be useful for the comprehensive assessment of morphological alterations of the corpus callosum in SCP.The corpus callosum volume,and median sagittal area may become neuroimaging references for the assess-ment of motor development in cerebral palsy(CP).

Trastuzumab deruxtecan(T-DXd)has demonstrated significant efficacy in clinical trials for human epidermal growth factor receptor 2(HER2)-expressing breast cancer,gastric cancer,lung cancer and other solid tumors.Its overall safety profile is manageable and tolerable,including the clinically concerning interstitial lung disease(ILD).The etiology of ILD is varied,among which drug-induced ILD is an exclusionary diagnosis.The incidence of ILD caused by different antitumor drugs varies with different symptoms,and the pathogenesis remains unclear.T-DXd-induced ILD is mostly Grades 1-2,and implementing a standardized clinical management protocol can reduce the incidence of severe ILD events,improve patient prognosis,and help maximize the clinical benefits of T-DXd.This article summarized the epidemiology,etiology,risk factors,and potential mechanisms of drug-induced ILD,with a focus on the incidence,time to onset,and outcomes of T-DXd-induced ILD after standardized clinical management.It aimed to help readers understand the importance of standardized clinical management before and during T-DXd treatment.Regarding specific clinical management strategies,the article reviewed comprehensive management approaches for T-DXd-induced ILD based on clinical trial protocols and real-world experiences from both domestic and international perspectives,covering patient screening,patient education,ILD monitoring,diagnosis,and treatment.Before initiating T-DXd treatment,patient screening helps identify those at high risk for ILD,and T-DXd should be used cautiously in these high-risk patients.Effective patient education can enhance patient initiative,encouraging them to promptly report suspected symptoms,which contributes to early identification of ILD.During T-DXd treatment,it is important to regularly monitor symptoms and signs related to ILD,implement regular imaging monitoring and leverage multidisciplinary team collaboration to diagnose ILD as early as possible,thereby minimizing the risk of severe ILD.If symptoms or imaging suggest ILD,T-DXd treatment must be immediately interrupted,and relevant examinations should be completed to rule out other possible causes while considering corticosteroid treatment.Upon ILD diagnosis,subsequent T-DXd dose adjustments,corticosteroid therapy,and supportive treatments should be guided by severity.The article also explored whether patients with T-DXd-induced ILD can be re-treated,concluding that Grade 1 ILD patients might be eligible for re-treatment under specific conditions.In conclusion,the article reviewed the epidemiology,characteristics,clinical trial-recommended management strategies,and real-world management measures of T-DXd-induced ILD,integrating clinical expert experiences to summarize and discuss comprehensive management strategies for it.This aimed to enhance clinicians'understanding of T-DXd-induced ILD and provide valuable insights for early identification,timely diagnosis,and proper management of it.

Objective:To construct influencing factors model of supply quality of medical equipment service based on grounded theory,so as to realize scientific,refined and standardized management of geriatric medical equipment. Methods:Based on the grounded theory of open coding,axial coding and selective coding,and taking the specific application of geriatric medical equipment as the core category,the influencing factor model of service supply quality was constructed to carry out total quality management of equipment. A total of 100 geriatric medical equipment in clinical use in Beijing Friendship Hospital were selected,and the equipment were managed from January to December 2021 by using conventional management methods,and the equipment were managed from January to December 2022 by using the grounded theoretical model. The self-designed recognition questionnaire was used to investigate the recognition scores of 4 engineers,6 doctors,10 nursing staff members,and 40 patients who used equipment for management. The defect rate of equipment management,use efficiency,management indicators,and multi-dimensional efficiency scores of the equipment were compared between the two management models. Results:The average scores of engineers,nurses,doctors,and patients who participated in the use management of grounded theoretical model were (92.25±2.14),(93.14±3.69),(92.56±3.14),and (93.58±4.36),respectively,which were higher than those of the conventional management model and the differences were statistically significant (t=18.897,13.729,12.843,9.826,P<0.05). After using the grounded theory model for management,there were 5,6,4,and 5 sets of equipment occurred packaging errors,missing equipment,damaged equipment,and insufficient supply,respectively. The defect rates of grounded theoretical model were 5％,6％,4％,and 5％,respectively,which were lower than those of the conventional management model. The differences were statistically significant (x2=6.438,12.706,11.054,10.286,P<0.05). The scores of equipment use efficiency,resource allocation,information basis,technical support,and management performance indicators of the grounded theory model were (92.68±5.36),(93.65±3.65),(94.26±4.01),(93.65±3.69),and (92.54±4.39),respectively. All were higher than those of the conventional management model,and the differences were statistically significant (t=8.729,16.856,12.113,15.593,10.358,P<0.05). The average scores for equipment use efficiency,maintenance efficiency,and repair efficiency under the management of grounded theory model were (93.65±3.26),(95.32±4.65),and (94.68±3.54),respectively,which were higher than those under the management of conventional management model,and the differences were statistically significant (t=19.915,12.362,10.686,P<0.05). Conclusion:The application of the factors model of supply quality of medical equipment service based on grounded theory can ensure the stability and safety of the equipment,and improve the quality of medical services and enhance the use efficiency of the equipment.

Objective:To construct influencing factors model of supply quality of medical equipment service based on grounded theory,so as to realize scientific,refined and standardized management of geriatric medical equipment. Methods:Based on the grounded theory of open coding,axial coding and selective coding,and taking the specific application of geriatric medical equipment as the core category,the influencing factor model of service supply quality was constructed to carry out total quality management of equipment. A total of 100 geriatric medical equipment in clinical use in Beijing Friendship Hospital were selected,and the equipment were managed from January to December 2021 by using conventional management methods,and the equipment were managed from January to December 2022 by using the grounded theoretical model. The self-designed recognition questionnaire was used to investigate the recognition scores of 4 engineers,6 doctors,10 nursing staff members,and 40 patients who used equipment for management. The defect rate of equipment management,use efficiency,management indicators,and multi-dimensional efficiency scores of the equipment were compared between the two management models. Results:The average scores of engineers,nurses,doctors,and patients who participated in the use management of grounded theoretical model were (92.25±2.14),(93.14±3.69),(92.56±3.14),and (93.58±4.36),respectively,which were higher than those of the conventional management model and the differences were statistically significant (t=18.897,13.729,12.843,9.826,P<0.05). After using the grounded theory model for management,there were 5,6,4,and 5 sets of equipment occurred packaging errors,missing equipment,damaged equipment,and insufficient supply,respectively. The defect rates of grounded theoretical model were 5％,6％,4％,and 5％,respectively,which were lower than those of the conventional management model. The differences were statistically significant (x2=6.438,12.706,11.054,10.286,P<0.05). The scores of equipment use efficiency,resource allocation,information basis,technical support,and management performance indicators of the grounded theory model were (92.68±5.36),(93.65±3.65),(94.26±4.01),(93.65±3.69),and (92.54±4.39),respectively. All were higher than those of the conventional management model,and the differences were statistically significant (t=8.729,16.856,12.113,15.593,10.358,P<0.05). The average scores for equipment use efficiency,maintenance efficiency,and repair efficiency under the management of grounded theory model were (93.65±3.26),(95.32±4.65),and (94.68±3.54),respectively,which were higher than those under the management of conventional management model,and the differences were statistically significant (t=19.915,12.362,10.686,P<0.05). Conclusion:The application of the factors model of supply quality of medical equipment service based on grounded theory can ensure the stability and safety of the equipment,and improve the quality of medical services and enhance the use efficiency of the equipment.

Trastuzumab deruxtecan(T-DXd)has demonstrated significant efficacy in clinical trials for human epidermal growth factor receptor 2(HER2)-expressing breast cancer,gastric cancer,lung cancer and other solid tumors.Its overall safety profile is manageable and tolerable,including the clinically concerning interstitial lung disease(ILD).The etiology of ILD is varied,among which drug-induced ILD is an exclusionary diagnosis.The incidence of ILD caused by different antitumor drugs varies with different symptoms,and the pathogenesis remains unclear.T-DXd-induced ILD is mostly Grades 1-2,and implementing a standardized clinical management protocol can reduce the incidence of severe ILD events,improve patient prognosis,and help maximize the clinical benefits of T-DXd.This article summarized the epidemiology,etiology,risk factors,and potential mechanisms of drug-induced ILD,with a focus on the incidence,time to onset,and outcomes of T-DXd-induced ILD after standardized clinical management.It aimed to help readers understand the importance of standardized clinical management before and during T-DXd treatment.Regarding specific clinical management strategies,the article reviewed comprehensive management approaches for T-DXd-induced ILD based on clinical trial protocols and real-world experiences from both domestic and international perspectives,covering patient screening,patient education,ILD monitoring,diagnosis,and treatment.Before initiating T-DXd treatment,patient screening helps identify those at high risk for ILD,and T-DXd should be used cautiously in these high-risk patients.Effective patient education can enhance patient initiative,encouraging them to promptly report suspected symptoms,which contributes to early identification of ILD.During T-DXd treatment,it is important to regularly monitor symptoms and signs related to ILD,implement regular imaging monitoring and leverage multidisciplinary team collaboration to diagnose ILD as early as possible,thereby minimizing the risk of severe ILD.If symptoms or imaging suggest ILD,T-DXd treatment must be immediately interrupted,and relevant examinations should be completed to rule out other possible causes while considering corticosteroid treatment.Upon ILD diagnosis,subsequent T-DXd dose adjustments,corticosteroid therapy,and supportive treatments should be guided by severity.The article also explored whether patients with T-DXd-induced ILD can be re-treated,concluding that Grade 1 ILD patients might be eligible for re-treatment under specific conditions.In conclusion,the article reviewed the epidemiology,characteristics,clinical trial-recommended management strategies,and real-world management measures of T-DXd-induced ILD,integrating clinical expert experiences to summarize and discuss comprehensive management strategies for it.This aimed to enhance clinicians'understanding of T-DXd-induced ILD and provide valuable insights for early identification,timely diagnosis,and proper management of it.

Parkinson's disease (PD) is the most common neurodegenerative movement disease. It is featured by abnormal alpha-synuclein (α-syn) aggregation in dopaminergic neurons in the substantia nigra. Macroautophagy (autophagy) is an evolutionarily conserved cellular process for degradation of cellular contents, including protein aggregates, to maintain cellular homeostasis. Corynoxine B (Cory B), a natural alkaloid isolated from Uncaria rhynchophylla (Miq.) Jacks., has been reported to promote the clearance of α-syn in cell models by inducing autophagy. However, the molecular mechanism by which Cory B induces autophagy is not known, and the α-syn-lowering activity of Cory B has not been verified in animal models. Here, we report that Cory B enhanced the activity of Beclin 1/VPS34 complex and increased autophagy by promoting the interaction between Beclin 1 and HMGB1/2. Depletion of HMGB1/2 impaired Cory B-induced autophagy. We showed for the first time that, similar to HMGB1, HMGB2 is also required for autophagy and depletion of HMGB2 decreased autophagy levels and phosphatidylinositol 3-kinase III activity both under basal and stimulated conditions. By applying cellular thermal shift assay, surface plasmon resonance, and molecular docking, we confirmed that Cory B directly binds to HMGB1/2 near the C106 site. Furthermore, in vivo studies with a wild-type α-syn transgenic drosophila model of PD and an A53T α-syn transgenic mouse model of PD, Cory B enhanced autophagy, promoted α-syn clearance and improved behavioral abnormalities. Taken together, the results of this study reveal that Cory B enhances phosphatidylinositol 3-kinase III activity/autophagy by binding to HMGB1/2 and that this enhancement is neuroprotective against PD.