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 analyze the transition patterns of anal sex and unprotected anal intercourse (UAI), estimate the transition intensity and probability, and identify factors influencing the transition patterns in men who have sex with men (MSM) in Shandong Province.Methods:In August 2019, MSM aged ≥18 years old were recruited as subjects from 11 cities in Shandong Province. The baseline survey were completed in December 2019, and followup surveys were conducted once every 3 mouths from June 2020 to March 2021. Time-continuous, state-discrete multi-state reversible Markov model was constructed based on the status of MSM's sexual behaviors with different types of sexual partners [anal sex occurred or not (S1=No, S2=Yes) and UAI occurred or not (S1=No,S2=Yes)] to analyze the transition patterns and the influencing factors.Results:A total of 735 MSM were included. The transition intensity of starting anal sex with stable and casual partners was 1.935 times and 0.595 times higher than that of discontinuing this behavior, respectively. While the transition intensity to start UAI with stable and casual partners was 0.430 times and 0.169 times higher than that of discontinuing it, respectively. During the follow-up, the transition probabilities of anal sex and UAI with both stable and casual partners increased first and then stabilized. For stable partners, the transition probability of starting anal sex was higher than that of discontinuing it at the same period, for casual partners, it was just the reverse. For both stable and casual partners, the transition probabilities of discontinuing UAI were higher than starting it at the same time. The results of multivariate analysis showed that participants who received intervention materials ( HR=1.47), had an associate degree ( HR=1.77) or a bachelor's degree and above ( HR=1.47) were at higher risk of starting anal sex with stable partners. Those who received intervention materials ( HR=1.39) were at higher risk of discontinuing anal sex with stable partners, while participants identified themselves as non-male gender ( HR=0.49) were at lower risk of discontinuing anal sex with stable partners. Participants received intervention materials ( HR=1.75) were at higher risk of starting UAI with stable partners. Those who lived apart, divorced, or widowed ( HR=3.22) were at higher risk of starting UAI with casual partners, whereas had a bachelor's degree and above ( HR=0.58) were at lower risk of starting UAI with casual partners. Participants identified themselves as non-male gender ( HR=0.45) at lower risk of discounting UAI with casual partners. Conclusions:The transition patterns of homosexual behavior in MSM are different. Marital status, gender identity, educational level and other factors are the influencing factors of sexual behavior status transitions. Future researches should develop targeted interventions for different types of sexual partners and characteristics of MSM.

Objective:To analyze the transition patterns of anal sex and unprotected anal intercourse (UAI), estimate the transition intensity and probability, and identify factors influencing the transition patterns in men who have sex with men (MSM) in Shandong Province.Methods:In August 2019, MSM aged ≥18 years old were recruited as subjects from 11 cities in Shandong Province. The baseline survey were completed in December 2019, and followup surveys were conducted once every 3 mouths from June 2020 to March 2021. Time-continuous, state-discrete multi-state reversible Markov model was constructed based on the status of MSM's sexual behaviors with different types of sexual partners [anal sex occurred or not (S1=No, S2=Yes) and UAI occurred or not (S1=No,S2=Yes)] to analyze the transition patterns and the influencing factors.Results:A total of 735 MSM were included. The transition intensity of starting anal sex with stable and casual partners was 1.935 times and 0.595 times higher than that of discontinuing this behavior, respectively. While the transition intensity to start UAI with stable and casual partners was 0.430 times and 0.169 times higher than that of discontinuing it, respectively. During the follow-up, the transition probabilities of anal sex and UAI with both stable and casual partners increased first and then stabilized. For stable partners, the transition probability of starting anal sex was higher than that of discontinuing it at the same period, for casual partners, it was just the reverse. For both stable and casual partners, the transition probabilities of discontinuing UAI were higher than starting it at the same time. The results of multivariate analysis showed that participants who received intervention materials ( HR=1.47), had an associate degree ( HR=1.77) or a bachelor's degree and above ( HR=1.47) were at higher risk of starting anal sex with stable partners. Those who received intervention materials ( HR=1.39) were at higher risk of discontinuing anal sex with stable partners, while participants identified themselves as non-male gender ( HR=0.49) were at lower risk of discontinuing anal sex with stable partners. Participants received intervention materials ( HR=1.75) were at higher risk of starting UAI with stable partners. Those who lived apart, divorced, or widowed ( HR=3.22) were at higher risk of starting UAI with casual partners, whereas had a bachelor's degree and above ( HR=0.58) were at lower risk of starting UAI with casual partners. Participants identified themselves as non-male gender ( HR=0.45) at lower risk of discounting UAI with casual partners. Conclusions:The transition patterns of homosexual behavior in MSM are different. Marital status, gender identity, educational level and other factors are the influencing factors of sexual behavior status transitions. Future researches should develop targeted interventions for different types of sexual partners and characteristics of MSM.

OBJECTIVE To evaluate the cost-effectiveness of clopidogrel versus aspirin monotherapy regimens for secondary prevention of ischemic stroke and to provide economic evidence and reference for clinical medication and decision-making. METHODS Based on the CAPRIE trial， a Markov model was constructed； the probabilities of risk events， health utility values， and costs of risk event management were obtained from relevant literature. The cycle length was 6 months， and the time horizon was 10 years. A discount rate of 5% per year was applied. The primary outcomes were total costs， quality-adjusted life-years （QALYs）， and incremental cost-effectiveness ratio （ICER）. Cost-utility analysis was performed for above 2 regimens by using TreeAge Pro software. The one-way sensitivity analysis， probabilistic sensitivity analysis and scenario analysis were conducted to validate the robustness of the analyses. RESULTS Compared with the aspirin regimen （325 mg/d of CAPRIE trial dose）， the ICER values of clopidogrel regimen for secondary stroke prevention for 10 years， 20 years and 30 years were 4 284.06， 4 201.20 and 3 986.78 yuan/QALY， respectively， which were E-mail：liuxiaoyanrj@sjtu.edu.cn all less than the willing-to-pay （WTP） threshold of one time 。 China’s per capita gross domestic product （GDP） in 2021. E-mail：scilwsjtu-wb@yahoo.com Compared with the aspirin regimen （clinically recommended dose in China， 100 mg/d）， the ICER values of clopidogrel regimen for stroke secondary prevention for 10 years， 20 years and 30 years were 58 238.27， 42 164.72 and 36 164.77 yuan/QALY， respectively， which were all less than WTP threshold. When comparing with aspirin regimen of 325 mg/d， results of one-way sensitivity analysis showed that the cost of clopidogrel and aspirin， probability of the first recurrence of ischemic stroke were sensitive factors of model. Results of probabilistic sensitivity analysis showed that when WTP was set at one time GDP per capita in China in 2021， clopidogrel had a probability of being cost- effective of about 66.5%. Results of scenario analysis showed that neither changing the time horizon to 10， 20 or 30 years nor using different doses of aspirin （50， 100， 150， 200 or 250 mg/d） would not alter any conclusions. CONCLUSIONS Compared with aspirin monotherapy， clopidogrel monotherapy is more cost-effective for secondary prevention of ischemic stroke.

Apoptosis is proved responsible for renal damage during ischemia/reperfusion. The regulation for renal apoptosis induced by ischemia/reperfusion injury (IRI) has still been unclearly characterized to date. In the present study, we investigated the regulation of histone acetylation on IRI-induced renal apoptosis and the molecular mechanisms in rats with the application of curcumin possessing a variety of biological activities involving inhibition of apoptosis. Sprague–Dawley rats were randomized into four experimental groups (SHAM, IRI, curcumin, SP600125). Results showed that curcumin significantly decreased renal apoptosis and caspase-3/-9 expression and enhanced renal function in IRI rats. Treatment with curcumin in IRI rats also led to the decrease in expression of p300/cyclic AMP response element-binding protein (CBP) and activity of histone acetyltransferases (HATs). Reduced histone H3 lysine 9 (H3K9) acetylation was found near the promoter region of caspase-3/-9 after curcumin treatment. In a similar way, SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), also attenuated renal apoptosis and enhanced renal function in IRI rats. In addition, SP600125 suppressed the binding level of p300/CBP and H3K9 acetylation near the promoter region of caspase-3/-9, and curcumin could inhibit JNK phosphorylation like SP600125. These results indicate that curcumin could attenuate renal IRI via JNK/p300/CBP-mediated anti-apoptosis signaling.

Apoptosis is proved responsible for renal damage during ischemia/reperfusion. The regulation for renal apoptosis induced by ischemia/reperfusion injury (IRI) has still been unclearly characterized to date. In the present study, we investigated the regulation of histone acetylation on IRI-induced renal apoptosis and the molecular mechanisms in rats with the application of curcumin possessing a variety of biological activities involving inhibition of apoptosis. Sprague–Dawley rats were randomized into four experimental groups (SHAM, IRI, curcumin, SP600125). Results showed that curcumin significantly decreased renal apoptosis and caspase-3/-9 expression and enhanced renal function in IRI rats. Treatment with curcumin in IRI rats also led to the decrease in expression of p300/cyclic AMP response element-binding protein (CBP) and activity of histone acetyltransferases (HATs). Reduced histone H3 lysine 9 (H3K9) acetylation was found near the promoter region of caspase-3/-9 after curcumin treatment. In a similar way, SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), also attenuated renal apoptosis and enhanced renal function in IRI rats. In addition, SP600125 suppressed the binding level of p300/CBP and H3K9 acetylation near the promoter region of caspase-3/-9, and curcumin could inhibit JNK phosphorylation like SP600125. These results indicate that curcumin could attenuate renal IRI via JNK/p300/CBP-mediated anti-apoptosis signaling.

Objective:To analyze, with Wuhan as an example, the problems found in the infrastructure development of China′s healthcare institutions, and put forward optimization suggestions for future epidemic prevention and control.Methods:From May to June 2020, we surveyed with questionnaires 56 healthcare institutions in Wuhan, covering such aspects as basic information of the institutions, infectious disease infrastructure readiness, and the converted wards for COVID-19. Statistical descriptions were used to analyze data so acquired.Results:The number of beds in the infectious departments of healthcare institutions in Wuhan amounted to 1.64 per 10 000 people, yet the existing 1 873 beds and about 5 000 convertible beds failed to meet the medical needs against the outbreak of COVID-19. After the outbreak, a total of 19 084 convertible beds were set up, of which general hospitals accounted for 88%; the area occupied by each converted bed in traditional Chinese medicine hospitals, hospitals of traditional and Western medicine, and maternal and child hospitals (<30.0m 2) was lower than that in general hospitals and specialist hospitals (>40.0m 2). Conclusions:Healthcare institutions should scientifically allocate " peacetime-wartime adaptive" hospital beds, optimize both the number and efficiency of these beds, and prepare for the worst scenarios, so that the infrastructure can be built and maintained in strict accordance with standards, government departments can rationally arrange infectious disease prevention and control facilities and strengthen their planning in case of emergencies.

Objective To investigate the effect of the treatment for Maisonneuve fracture with arthroscopicassistant plate-screw fixation ofsyndesmosis.Methods From January 2015 to December 2016,totally 22 patients with Maisonneuve fracture were treated in Shanghai Jiao Tong University Affiliated Six People's Hospital.Eleven patients in minimal invasive surgery (MIS)group were treated by the arthroscopic-assistant plate-screw fixation ofthe syndesmotic injury.Another 11 patients in the control group were performed a classic syndesmosis screw fixation.Plain radiographic examination was carried out during the follow-up.Functional evaluation was measured according to the American Orthopedic Foot Ankle Society (AOFAS) ankle hindfoot score and the Visual analogue scale(VAS).A t test was applied for the statistic analysis of post-operative outcome between the two groups at 6th and 12th month.Results The patients were followed for an average 18 months (range from 12 to 24 months)except one of MIS group.The X-ray demonstrated the solid bone union occurred on the 12th week in MIS group and 12.5th week in the control group.The implants of syndesmosis were removed at 12th week post-operatively.No cases of re-diastasis occurred during the follow-up.There was significant difference with in the groups.In the MIS group,the AOFAS ankle hindfoot score was (85.9 ±4.1) points at 6th month post-operatively,and increased to (90.8 ± 3.7) at 12th month (P ＜ 0.05).VAS score was (2.4 ± 1.2) at 6th month and (1.1 ± 0.7) at 12th month after the operation(P ＜0.05).In the control group,the AOFAS ankle hindfoot score was (81.1 ±4.7) points at 6th month after operation,and increased to (89.1 ± 3.4) at 12th month after operation (P ＜ 0.05).VAS score was (3.2 ± 1.3) at the 6th month and (1.0 ± 1.0) at the 12th month after operation (P ＜ 0.05).However,for the outcome comparison between the two groups,only the AOFAS ankle hindfoot score of 6th month post-operatively in MIS group was better than the control group (P ＜ 0.05),other results,had no significant difference.Nocomplications of implant failure,nonunion,malunion or post-traumatic arthritis were occurred during the followup.Conclusion The treatment of Maisonneuve fracture by arthroscopic-assistant plate-screw fixation proved to have an advantage of minimal invasion and accurate reduction and fixation,which is a safe and effective surgical method.

Objective To investigate the effect of tiaozhi granules on the autophagy of HU-VECs in the cell,protein and molecular levels.Methods HUVECs were induced by tiaozhi granule medicated serum,6-amino-3-methyl purine (3-MA) and rapamycin.MTT was used to detect the cell viability after 48 hours with tiaozhi granule medicated serum.Western blot was used to detect the expressive level of LC3-Ⅱ.Immunofluorescence was used to detect change in the numbers of autophagosomes.Results After HUVECs was processed by tiaozhi granule medicated serum,the cell viability had not change,the relative expression of autophagy related protein LC3-Ⅱ increased,and the number of autophagosomes increased (P ＜ 0.05).After HUVECs was processed by tiaozhi granule medicated serum and rapamycin,cell viability had no change,while the relative expression of autophagy related protein LC3-Ⅱ and the number of autophagosomes decreased significantly when compared with the results of intervention with rapamycin only (P ＜ 0.05 or P ＜ 0.01).Conclusion Tiaozhi granules can inhibit excessive autophagy of endothelial cells and promote moderate autophagy in endothelial cells.

Objective To investigate the effect of tiaozhi granules on the autophagy of HU-VECs in the cell,protein and molecular levels.Methods HUVECs were induced by tiaozhi granule medicated serum,6-amino-3-methyl purine (3-MA) and rapamycin.MTT was used to detect the cell viability after 48 hours with tiaozhi granule medicated serum.Western blot was used to detect the expressive level of LC3-Ⅱ.Immunofluorescence was used to detect change in the numbers of autophagosomes.Results After HUVECs was processed by tiaozhi granule medicated serum,the cell viability had not change,the relative expression of autophagy related protein LC3-Ⅱ increased,and the number of autophagosomes increased (P ＜ 0.05).After HUVECs was processed by tiaozhi granule medicated serum and rapamycin,cell viability had no change,while the relative expression of autophagy related protein LC3-Ⅱ and the number of autophagosomes decreased significantly when compared with the results of intervention with rapamycin only (P ＜ 0.05 or P ＜ 0.01).Conclusion Tiaozhi granules can inhibit excessive autophagy of endothelial cells and promote moderate autophagy in endothelial cells.