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

Dental implant is a commonly used therapeutic option for reconstruction of edentulous space. Adequate peri-implant soft tissue is crucial for preventing biological and esthetic complications. Peri-implant soft-tissue phenotypes including supracrestal tissue height, mucosa thickness and keratinized mucosa width could reflect the quality and quantity of peri-implant soft tissue. Different soft-tissue phenotypes might impact the stability of implant restoration through altering the tissue remodeling or inflammatory response. This review will discuss the influence of peri-implant soft-tissue phenotypes on tissue remodeling and inflammatory response after implant placement.

Objective:To analyze the results of the practice test and formal test of the annual professional proficiency test for residents in 2022, to investigate related influencing factors and the effectiveness of the practice test, and to propose the measures for improving the results of the annual professional proficiency test.Methods:The scores of the annual professional proficiency test were analyzed for 202 residents who participated in the test in 2022, and the data on sex, education background, type of personnel, whether they passed the medical licensing examination, and practice test scores were analyzed to investigate related influencing factors. SPSS 23.0 and GraphPad Prism 8 were used for the chi-square test, the t-test, the one-way of variance, and the Fisher's exact test. A multiple linear regression analysis was used to identify influencing factors, and a Pearson correlation analysis was also performed. Results:The scores of the annual professional proficiency test for 202 residents were normally distributed with the highest number of the residents with a score of 90-99 points and the lowest number of the residents with a score of <70 points. The residents who passed the medical licensing examination had a significantly higher score of the annual professional proficiency test than those who failed the examination ( t=2.87, P=0.005), and the residents who passed the three practice tests had a significantly higher score of the annual professional proficiency test than those who failed the practice tests ( P<0.05). The score of the second practice test, the score of the third practice test, and the passing of medical licensing examination were independent influencing factors for the score of annual professional proficiency test ( R2=0.236, R2=0.201, F=6.60, P<0.05). The correlation analysis showed that the scores of the three practice tests were positively correlated with the final score ( r=0.189, 0.373, and 0.311, P<0.05). Conclusions:Improving the passing rate of medical licensing examination and strengthening pre-examination practice tests can help to improve the score of annual professional proficiency test. At the same time, it is necessary to improve the quality of training through the measures such as strengthening the homogenization management of different types of students, improving the attention and enthusiasm of all levels, and accelerating the construction of question banks.

Objective:This study aimed to assess the effects of Peer Balint-style group on the empathy ability of third-year long-term medical students and to provide a theoretical and practical reference for effectively improving their humanistic quality.Methods:Ninety third-year Chinese long-term medicine students participated. Volunteers received either ten sessions of 1.5-h Peer Balint-style group which were led by specially trained peers from June 2019 to August 2019. The College Students' Empathy Ability Questionnaire was used before the experiment and the second day after the experiment. The total score of the scale from the pre-test and post-test and the scores of each dimension conformed to a normal distribution, with equal variance, describing in the form of ( x± s). Paired t-tests were performed to compare the total score and each dimension score before and after the intervention, using SPSS 22.0. Semi-structured interviews were conducted with 7 peer-group leaders and group members after the clinical practice period. The interview materials were analyzed by traditional content analysis. The content of the qualitative research was open-coded to obtain 10 categories, suggesting the role and inadequacy of Peer Balint-style groups. Results:A total of 63 valid samples were obtained. There was no significant difference of ( t=-0.44, P=0.661, P>0.05) between the total score of the post-test (118.00±11.98) and the total score of the pre-test (117.38±12.36). In each dimension, the reverse comprehension score of post-test (9.06±1.97) was significantly different ( t=-2.08, P=0.041, P>0.05) from the pre-test's (8.57±2.15), which increased compared to the pre-test score. Conclusions:Peer Balint-style group had a positive effect on improving empathy among medical students. Compared with the traditional Balint group, it has wider coverage, higher affinity and greater mobility. However, the design of the Peer Balint-style group still needs to be further improved.

ObjectiveTo investigate the mechanisms of Panax notoginseng saponins （PNS） in inhibiting high shear-induced platelet aggregation and thrombosis via the Piezo1-mediated calcium signaling pathway. MethodBioflux1000z was used for the microfluidic assay， where platelets were stimulated with physiological shear rate （500 s^-1）， pathological shear rate （12 000 s^-1）， or Piezo1 agonist Yoda1 under the physiological shear rate （500 s^-1）. The shear-induced platelet calcium influx and the binding of platelet with von Willebrand factor （vWF） were measured by flow cytometry. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the vWF release from platelets. The microfluidic channels were used to determine the vWF-mediated platelet aggregation and integrin αⅡbβ3 activation. A mouse model of arterial thrombosis induced by high shear stress combined with endothelial injury was established. The ultrasonic Doppler flow meter was used to monitor the cyclic flow reduction （CFR） caused by the repeated formation and shedding of thrombi， and flow cytometry was employed to examine platelet-vWF binding， on the basis of which the effect of PNS on high shear-induced arterial thrombosis was evaluated. ResultThe microfluidic assay showed that PNS decreased the high shear rate （12 000 s^-1） or Yoda1-induced calcium influx， platelet-vWF binding， vWF-mediated platelet-fibrinogen binding， and vWF release from platelet alpha-granules in a dose-dependent manner. In the mouse model of high shear-induced thrombosis， PNS markedly reduced the CFR and occlusion time of the common carotid artery and inhibited platelet-vWF binding. ConclusionPNS can mitigate pathological shear-induced platelet aggregation and arterial thrombosis via influencing Piezo1/GPIbα-vWF signaling.

The conventional oral drug delivery frequently results in the drug elimination before its complete release due to rapid gastric emptying and short gastrointestinal transport time, thus reducing the bioavailability of drug. In order to maintain an effective concentration of drug in the body and maximize its optimal efficacy, the frequency of administrations often needs to be increased. By contrast, gastric retention drug delivery system (GRDDS), as an innovative method of drug delivery, prolongs the retention time of the drug in the stomach and reduces irritation to the gastrointestinal tract. Consequently, it enhances the bioavailability of drug, reduces dosing frequency for patients and improves treatment adherence. In recent years, domestic and foreign studies have been conducted on gastric retention drug delivery systems. Here, we provide a comprehensive overview of the relevant literature published in recent years, examining their current marketing status, various types, as well as in vivo and in vitro evaluation methods.

From an aqueous extract of the Angelica sinensis root head (guitou), nine pairs of lignanoid enantiomers [(+)-/(-)-1-(+)-/(-)-9], including three pairs of new structures [(+)-/(-)-1-(+)-/(-)-3] and two pairs of chiral separated enantiomers for the first time [(+)-/(-)-4 and (+)-/(-)-5], were isolated and chirally separated by column chromatography over different types of resin, normal and reversed phase silica gels, together with HPLC techniques using reversed phase and chiral columns. Their structures were determined by spectroscopic data analysis, theoretic calculation of electronic circular dichroism (ECD) spectra, and single-crystal X-ray diffraction. The chiral separated new enantiomers named (+)-/(-)-angelignanins Q-T [(+)-/(-)-1-(+)-/(-)-4] and (+)-/(-)-daphneresinol [(+)-/(-)-5], respectively.

Objective To investigate the relationship between single nucleotide polymorphisms(SNPs)in the eNOS gene and genetic susceptibility to systemic lupus erythematosus(SLE)in Hainan.Methods Blood samples were collected from SLE patients(SLE group,n=214)and healthy controls(control group,n=214)from January 2020 to December 2022 at the First Affiliated Hospital of Hainan Medical College and Hainan Provincial People's Hospital.The bases of eNOS gene rs3918188,rs1799983 and rs1007311 loci in each group were detected by SNaPshot sequencing technology.Logistic regression was used to analyze the correlation between genotypes,alleles and gene models(dominant model,recessive model,and overdominant model)of the above 3 target loci of the eNOS gene and genetic susceptibility to SLE.Haplotype analysis was conducted using HaploView 4.2 software to investigate the relationship between haploid and genetic susceptibility to SLE at each site.Results The results of logistic regression analysis revealed that the CC genotype and the C allele at rs3918188 locus were risk factors for genetic susceptibility to SLE(CC vs.AA:OR=2.449,P<0.05;C vs.A:OR=2.133,P<0.001).In recessive model at rs3918188 locus,CC genotype carriers had an increased risk of SLE development compared with AA+AC genotype carriers(OR=2.774,P<0.001).In contrast,in overdominant model at this locus,AC genotype carriers had a decreased risk of SLE occurrence compared with AA+CC genotype carriers(OR=0.385,P<0.001).In addition,polymorphisms of rs1799983 and rs1007311 were not associated with susceptibility to SLE in genotype,allele type and the 3 genetic models(P>0.05).Haplotype analysis revealed a strong linkage disequilibrium between the rs1007311 and rs1799983 loci of the eNOS gene,but no significant correlation was found between haplotype and genetic susceptibility to SLE(P>0.05).Conclusion The CC genotype and C allele at rs3918188 locus of eNOS gene may be risk factors for SLE in Hainan,while the risk of SLE occurrence is reduced in carriers of AC genotype under the overdominant model.

Aim To investigate the intracellular up-take and target protein binding characteristics of two Bruton's tyrosine kinase inhibitors(BTKi)with differ-ent selectivities to provide further insights into the mechanisms of drug off-target-related bleeding risk.Methods Ibrutinib(non-selective BTKi)and za-nubrutinib(selective BTKi)were used as study drugs.After incubation of MEC-1 cells and human platelets with drugs,the cellular thermal shift assay(CETSA)was combined with Western blot to obtain the melting curve and isothermal curve to analyze the binding char-acteristics of the two drugs with the target protein BTK.After incubation of MEC-1 cells and human platelets with drugs,the concentrations of the two drugs were detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS)to analyze the intracellular uptake of the two drugs.Results CETSA analysis confirmed that zanubrutinib was more selective for the target protein BTK compared to ibrutinib.LC-MS/MS analysis showed that both drugs were uptaken intracel-lularly by MEC-1 cells and platelets in a concentration-dependent manner.Conclusions While BTKi targe-ting BTK to B lymphocytes exerts therapeutic effects,off-target effects on platelets due to differences in their intracellular uptake,and target-binding characteristics may be one of the reasons for the differences in bleed-ing risk across selective BTKi.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.