Astrocytes are the largest glial population in the mammalian brain. However, we have a minimal understanding of astrocyte development, especially fate specification in different regions of the brain. Through lineage tracing of the progenitors of the third ventricle (3V) wall via in-utero electroporation in the embryonic mouse brain, we show the fate specification and migration pattern of astrocytes derived from radial glia along the 3V wall. Unexpectedly, radial glia located in different regions along the 3V wall of the diencephalon produce distinct cell types: radial glia in the upper region produce astrocytes and those in the lower region produce neurons in the diencephalon. With genetic fate mapping analysis, we reveal that the first population of astrocytes appears along the zona incerta in the diencephalon. Astrogenesis occurs at an early time point in the dorsal region relative to that in the ventral region of the developing diencephalon. With transcriptomic analysis of the region-specific 3V wall and lateral ventricle (LV) wall, we identified cohorts of differentially-expressed genes in the dorsal 3V wall compared to the ventral 3V wall and LV wall that may regulate astrogenesis in the dorsal diencephalon. Together, these results demonstrate that the generation of astrocytes shows a spatiotemporal pattern in the developing mouse diencephalon.
Mice ; Animals ; Astrocytes ; Neuroglia/physiology* ; Diencephalon ; Brain ; Neurons ; Mammals

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.

Objective:To investigate the clinical efficacy of liver transplantation for intra-hepatic cholangiocarcinoma.Methods:The retrospective cohort study was conducted. The clinico-pathological data of 22 patients with intrahepatic cholangiocarcinoma who underwent liver trans-plantation in the 5 medical centers, including First Hospital of Jilin University, et al, from September 2005 to December 2021 were collected. There were 18 males and 4 females, aged 57(range, 38?71)years. Observing indicators: (1) clinicopathological characteristics of patients with intrahepatic cholangiocarcinoma; (2) follow-up; (3) prognosis. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages. The Kaplan-Meier method was used to draw survival curves. The Log-Rank test was used for survival analysis. Results:(1) Clinicopathological characteristics of patients with intrahepatic cholangio-carcinoma. Of the 22 patients, 20 cases were diagnosed as intrahepatic cholangiocarcinoma before liver transplantation, 7 cases had viral hepatitis type B, 1 case had primary sclerosing cholangitis, 7 cases had tumor treatment before liver transplantation, 7 cases, 6 cases and 9 cases were classified as grade A, grade B and grade C of the Child-Pugh classification, 16 cases had preoperative CA19-9 >40 U/mL, 14 cases had single tumor, 11 cases with tumor located at right lobe of liver, 6 cases with tumor located at both left and right lobe of liver, 5 cases with tumor located at left lobe of liver, 9 cases with tumor vascular invasion. All 22 patients were diagnosed as moderate-poor differentiated tumor. There were 9 cases with liver cirrhosis, 4 cases with tumor lymph node metastasis, 10 cases with tumor burden within Milan criteria. The tumor diameter of 22 patients was 4.5(range, 1.5?8.0)cm. (2) Follow-up. All 22 patients were followed up for 15(range, 3?207)months. Of the 22 patients, 9 cases had tumor recurrence and 8 cases died. (3) Prognosis. The 1-year overall survival rate and 1-year disease-free survival rate of the 22 patients was 72.73% and 68.18%, respectively. Results of subgroup analysis showed there were significant differences in overall survival and disease-free survival between the 10 patients with tumor burden within Milan criteria and the 12 patients with tumor burden beyond Milan criteria who underwent liver transplantation ( hazard ratio=0.13, 0.26, 95% confidence interval as 0.03?0.53, 0.08?0.82, P<0.05). Results of further analysis of the 12 patients with tumor burden beyond Milan criteria showed there were significant differences in overall survival and disease-free survival between the 5 patients with preoperative tumor down-staging treatment and the 7 patients without preoperative tumor down-staging treatment ( hazard ratio=0.18, 0.14, 95% confidence interval as 0.04?0.76, 0.04?0.58, P<0.05). Conclusions:Intrahepatic cholangiocarcinoma patients with tumor burden within Milan criteria have a better prognosis than patients with tumor burden beyond Milan criteria after liver transplantation. For patients with tumor burden beyond Milan criteria, active tumor down-staging treatment before liver transplantation can improve the prognosis.

In mammals, the piezoelectric protein, Prestin, endows the outer hair cells (OHCs) with electromotility (eM), which confers the capacity to change cellular length in response to alterations in membrane potential. Together with basilar membrane resonance and possible stereociliary motility, Prestin-based OHC eM lays the foundation for enhancing cochlear sensitivity and frequency selectivity. However, it remains debatable whether Prestin contributes to ultrahigh-frequency hearing due to the intrinsic nature of the cell's low-pass features. The low-pass property of mouse OHC eM is based on the finding that eM magnitude dissipates within the frequency bandwidth of human speech. In this study, we examined the role of Prestin in sensing broad-range frequencies (4-80 kHz) in mice that use ultrasonic hearing and vocalization (to >100 kHz) for social communication. The audiometric measurements in mice showed that ablation of Prestin did not abolish hearing at frequencies >40 kHz. Acoustic associative behavior tests confirmed that Prestin-knockout mice can learn ultrahigh-frequency sound-coupled tasks, similar to control mice. Ex vivo cochlear Ca²⁺ imaging experiments demonstrated that without Prestin, the OHCs still exhibit ultrahigh-frequency transduction, which in contrast, can be abolished by a universal cation channel blocker, Gadolinium. In vivo salicylate treatment disrupts hearing at frequencies <40 kHz but not ultrahigh-frequency hearing. By pharmacogenetic manipulation, we showed that specific ablation of the OHCs largely abolished hearing at frequencies >40 kHz. These findings demonstrate that cochlear OHCs are the target cells that support ultrahigh-frequency transduction, which does not require Prestin.
Animals ; Cochlea/metabolism* ; Hair Cells, Auditory, Outer/metabolism* ; Hearing ; Humans ; Mammals/metabolism* ; Mice ; Mice, Knockout ; Molecular Motor Proteins/metabolism*

Objective:To develop a novel posterior circulation score (PCS) based on pretreatment diffusion-weighted imaging (DWI) for predicting futile recanalization (FR) of acute basilar artery occlusion (BAO) after endovascular therapy (EVT).Methods:A prospectively registered consecutive cohort of BAO patients treated with EVT in Beijing Tiantan Hospital, Capital Medical University during a six-year period was reviewed. This novel DWI-based PCS (DWI-PCS) was calculated according to the characteristics of acute infarction at four sites (pons, midbrain, thalamus and cerebellum), with a normal score of 0 point and a full score of 16 points. FR was defined as the occurrence of poor outcome (modified Rankin Scale score>3) at 90 days despite successful recanalization (modified Thrombolysis In Cerebral Infarction ≥ 2b) at final angiogram after EVT. The independent association of DWI-PCS with FR was evaluated by multivariable Logistic regression, and the predictive discrimination of DWI-PCS was measured by the area under the receiver operating characteristic (ROC) curve. Additionally, the effects of DWI-PCS on FR in different subgroups stratified by age, time window, stroke severity and etiology were explored.Results:Of 109 patients in this study, 48 (44.0%) suffered from FR. The multivariable Logistic analysis showed that DWI-PCS was significantly associated with FR (adjusted OR=1.31, 95% CI 1.07-1.62, P=0.01). The ROC curve analysis demonstrated that the area under the curve of DWI-PCS for predicting FR was 0.74 (95% CI 0.65-0.83), and the optimal cut-off value was ≥ 3 points (sensitivity 0.75, specificity 0.66, accuracy 0.70). Finally, the effects of DWI-PCS on FR were not found to be different across all subgroups ( P>0.10 for all interactions). Conclusions:The novel DWI-PCS may be a valid and reliable predictor of FR in BAO patients treated with EVT. Nevertheless, external validation with blinded outcome is still needed to confirm its performance before clinical application.

Objective To evaluate the safety of morphine hydrochloride injection. Methods Ear verin injection was used to evaluate the vascular irritation using the comparison of left side with right side in rabbits. Quadriceps femoris injection was used to evaluate the muscle irritation using the comparison of left side with right side in rabbits. Guinea pigs were intravenously injected with morphine hydrochloride injection at a dose of 2.8 mg·kg-1 once daily 3 times, stimulation was performed on 14 d after the last sensitization and the booster dose was 2 times the sensitization dose. The allergic reactions were observed. The different concentrations of morphine hydrochloride injection were placed in 2％ rabbit erythrocyte suspension, and then the hemolyzation and agglutination were observed. Results There were no significant vascular or muscular irritation and injury effects of morphine hydrochloride injection in rabbits. There were no evidenceof hemolyzation and agglutination in rabbit erythrocytes in vitro. No allergic reactions on guinea pigs in vivo were observed. Conclusion After treatment of morphine hydrochloride injection, neither obvious vascular /muscle stimulation or sensitization, nor hemolyzation or agglutination appeared in rabbits. The research results provide basic reference for the clinical rational and safe application of morphine hydrochloride injection.

Eukaryota ; Molecular Dynamics Simulation ; Permeability ; Protein Conformation ; Sodium ; metabolism ; Substrate Specificity ; Voltage-Gated Sodium Channels ; chemistry ; metabolism

Objective To evaluate the efficacy of the traditional Chinese medicine NAOAN capsule in primary prevention of stroke in high?risk populations. Methods A multicenter, randomized controlled study was performed in community setting, involving 1 088 individuals at high risk of stroke, with cerebrovascular function scores<75 and 10?year Framingham stroke risk ≥6%. Subjects were recruited in communities at Beijing, Shanghai, Changsha, and Chengdu communities, through resident committees or the village unit. A total of 559 subjects were randomized into a group treated with the NAOAN capsule, and 529 subjects in an aspirin treatment group. Follow?up was performed every 2 months for 2 years. At the mid?point and end of the intervention, we compared cerebrovascular function differences between the 2 groups. Results During the 2?year community trial, 531 subjects in the NAOAN capsule group and 465 in the aspirin group followed the protocol. Cerebrovascular function scores increased from 45.2±19.7 at baseline to 61.7±26.5 after the 2?year trial (t=－12.931, P<0.001) in the NAOAN capsule group, and from 47.2±18.9 at baseline to 53.7 ± 25.1 (t=－5.058, P<0.001) in the aspirin group; greater increases in cerebrovascular function scores were found in the NAOAN capsule group than that in the aspirin group (t=4.906, P<0.001). Conclusions Cerebrovascular function in individuals at high risk of stroke was improved by taking NAOAN capsule. Cerebrovascular function scores improved more with NAOAN capsules than with aspirin.

Objective: To investigate the efficacy of sequential treatment with first-line administration of second-generation tyrosine kinase inhibitors (TKI) and first-generation TKI (imatinib) in patients with Ph⁺ acute lymphoblastic leukemia (Ph⁺ ALL) followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Retrospective analysis of clinical features and prognosis of 76 newly diagnosed Ph ⁺ALL patients from June 2011 to December 2015 treated by allo-HSCT combined with first-line administration of second-generation or first-generation TKI was performed and the efficacy compared. Results: Of 76 Ph⁺ ALL patients, first-generation TKI was administered in 57 cases, second-generation TKI in 19 cases, including 10 cases of nilotinib and 9 cases of dasatinib. There was no significant difference in age, WBC counts, additional chromosomal abnormalities, time form diagnosis to transplantation, transplantation type, conditioning regimen or TKI initiation time between the two groups. Complete remission (CR) rates at the fourth week of induction therapy in first-generation TKI group and second-generation TKI group was 93.0% and 94.7% (P=1.000), respectively. Major molecular response (MMR, BCR-ABL/ABL reduce 3 log) rates meanwhile were 46.0% and 40.0% (χ²=0.169, P=0.681). Relapse rates before transplantation were 14.0% and 10.5% (P=1.000). MMR rates before transplantation were 54.4% and 68.2% (χ²=1.152, P=0.283). The 2-year overall survival (OS) rates of first-generation and second-generation TKI group were 62.0% and 94.7% (χ²=5.765, P=0.016), 2-year event-free survival (EFS) rates were 46.3% and 84.2% (χ²=5.644, P=0.018), respectively. Univariate analysis showed that second-generation TKI could improve OS (HR=0.126, 95%CI 0.017-0.939, P=0.043). Multiple factors analysis showed that second-generation TKI (HR=0.267, 95%CI 0.081-0.873, P=0.029) and MMR before transplantation (HR=0.496, 95%CI 0.254-0.968, P=0.040) were good independent prognostic factors of EFS. Conclusions There was significant difference in the efficacy of second-generation TKI and first-generation TKI for Ph⁺ ALL patients treated by allo-HSCT. First-line administration of second-generation TKI showed better efficacy than that of first-generation TKI for Ph⁺ ALL patients.

Objective: To investigate the efficacy of first-line administration of generic dasatinib or first-generation TKI (imatinib) in patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph⁺ ALL) treated by hematopoietic stem cell transplantation (HSCT). Methods: Clinical features and prognoses of 63 newly diagnosed Ph⁺ ALL patients from Jan 2014 to June 2017 treated by HSCT combined with first-line administration of generic dasatinib or imatinib were retrospective analyzed. Results: Of 63 Ph⁺ ALL patients, 31 cases were administered generic dasatinib, and the other 32 ones imatinib. Complete remission (CR) rates at the fourth week of induction therapy in generic dasatinib and imatinib groups were 96.8% and 93.8% (P=1.000) , respectively. Meanwhile major molecular response (MMR; BCR-ABL/ABL reduce 3log) rates were 41.9% and 43.8% (χ²=0.021, P=0.884), respectively. Relapse rates before transplantation were 6.5% and 12.5% (P=0.672), respectively. MMR rates before HSCT were 83.9% and 68.8% (χ²=1.985, P=0.159), respectively. The 20-monthes overall survival (OS) rates of generic dasatinib and imatinib groups were 95.5% and 76.5% (χ²=0.990, P=0.320) respectively; 20-monthes event-free survival (EFS) rates were 93.5% and 61.4% (χ²=5.926, P=0.015), respectively. Statistically significant differences of EFS were reached. Multiple factors analysis showed that generic dasatinib (HR=0.201, 95% CI 0.045-0.896, P=0.035) and MMR before transplantation (HR=0.344, 95% CI 0.124-0.956, CI=0.041) could improve EFS. Conclusions First-line administration of generic dasatinib could improve EFS for Ph⁺ALL patients treated by HSCT when compered with imatinib.