Autism Spectrum Disorders (ASDs) are reported as a group of neurodevelopmental disorders. The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with dysfunction of ASD risk genes, but the underlying mechanisms are not fully understood. Here, we report that deletion of Trio, a high-susceptibility gene of ASDs, causes a postnatal dentate gyrus (DG) hypoplasia with a zigzagged suprapyramidal blade, and the Trio-deficient mice display autism-like behaviors. The impaired morphogenesis of DG is mainly caused by disturbing the postnatal distribution of postmitotic granule cells (GCs), which further results in a migration deficit of neural progenitors. Furthermore, we reveal that Trio plays different roles in various excitatory neural cells by spatial transcriptomic sequencing, especially the role of regulating the migration of postmitotic GCs. In summary, our findings provide evidence of cellular mechanisms that Trio is involved in postnatal DG morphogenesis.
Animals ; Dentate Gyrus/metabolism* ; Mice ; Morphogenesis/physiology* ; Neurons/pathology* ; Cell Movement ; Mice, Inbred C57BL ; Autism Spectrum Disorder/pathology* ; Mice, Knockout ; Neural Stem Cells ; Male ; Neurogenesis ; Autistic Disorder/genetics*

Objective:To investigate the patterns of mutation evolution in patients with acute myeloid leukemia (AML) during treatment and the possible clinical significances.Methods:A retrospective case series study was conducted. A total of 103 AML patients who were hospitalized at the Affiliated Yuebei People's Hospital of Medical College of Shantou University from November 2019 to August 2021 and underwent high-throughput next-generation sequencing (NGS) technology to detect the mutations of 128 AML-related genes in bone marrow samples were selected. Based on the NGS results, the somatic gene mutations in samples of patients collected at initial diagnosis (73 cases), complete remission (CR) (30 cases), non-remission (NR) (23 cases), and recurrence (12 cases) were analyzed, and the targeted drugs involved in the gene mutations detected in NR and recurrence samples were summarized.Results:The median age [ M ( Q1, Q3)] of onset for 103 patients was 58 (48, 66) years, including 64 males (61%) and 39 females (39%); 86 cases (83%) were primary AML, and 17 cases (17%) were secondary AML; at the initial diagnosis, 51 cases (50%) had normal karyotypes, 34 cases (33%) had abnormalities, and 18 cases (17.5%) were unknown. Compared with the CR samples, the mutation frequencies of FLT3 [29% (21/73) vs. 3% (1/30)], NPM1 [27% (20/73) vs. 3% (1/30)], NRAS [22% (16/73) vs. 3% (1/30)], and IDH2 [14% (10/73) vs. 0 (0/30)] were all higher in the initial diagnosis samples, and the differences were statistically significant (all P < 0.05); compared with the initial diagnosis sample, the median number of gene mutations in each CR sample was lower [4 (2, 5) vs. 7 (5, 9)], and the difference was statistically significant ( P < 0.001). However, there was no statistically significant difference in the median number of gene mutations in each patient between the initial diagnosis samples and the NR samples, the initial diagnosis samples and the recurrence samples, and the NR samples and the recurrence samples (all P > 0.05). Analysis of 14 patients with NGS data at initial diagnosis and CR showed that the same gene mutations could be detected at initial diagnosis and CR, such as DNAH23 (3 cases), USH2A (3 cases), etc; partial gene mutations were detected at initial diagnosis but were not detected at CR, including NRAS (5 cases), FLT3 (3 cases), ANKRD26 (3 cases), NPM1 (3 cases), ETV6 (3 cases), etc; ARID1B (1 case) and DNMT3A (1 case) were negative for mutations at initial diagnosis but positive upon reaching CR. Analysis of 14 patients with NGS data at initial diagnosis and NR showed that most gene mutations persisted at initial diagnosis and NR, such as DNMT3A (5 cases), NRAS (5 cases), KRAS (3 cases), RUNX1 (3 cases), etc; the mutant genes detected at initial diagnosis but not detected at NR included USH2A (2 cases), PCLO (2 cases), ATM (2 cases), FAT1 (2 cases), etc; partial gene mutations were not detected at initial diagnosis but were detected at NR, such as FAT1 (2 cases), TCF3 (2 cases), etc. Analysis of 5 patients with NGS data at CR and recurrence showed that some gene mutations were detected at both CR and recurrence, such as BCORL1 (1 case), ARID2 (1 case), SETD2 (1 case), VEGFC (1 case), etc; FLT1 (1 case) and GNAS (1 case) gene mutations were detected at CR but not detected at recurrence; at recurrence, some gene mutations that were not detected at CR were also detected, such as ANKRD26 (1 case), WT1 (1 case), etc. Among the 23 NR samples and 12 recurrence samples, the targets of drugs approved by US Food and Drug Administration or in clinical trials were detected in 14 (61%) and 5 (42%) samples respectively, including IDH1, IDH2, FLT3, KIT, KRAS, NRAS, SF3B1, U2AF1, and SRSF2. Conclusions:The number of gene mutations in AML patients during CR is significantly less than that at initial diagnosis, some gene mutations disappear when CR is achieved through treatment, but the majority of gene mutations persist during the treatment period, including NR and recurrence, suggesting that monitoring through NGS technology can help understand the evolution of gene mutations during AML treatment and discover the potential therapeutic targets.

Objective To identify mechanisms regulating disease progression in rat models of pulmonary arterial hy-pertension(PAH).Methods Rat PAH models were established using subcutaneous monocrotaline(MCT)injec-tion and the SU5416/hypoxia(SU/Hx)method.Transcriptomic sequencing of lung tissues was performed to identify gene expression and pathway alterations in PAH rats,followed by a comparative analysis with transcriptomic data of patients with idiopathic pulmonary arterial hypertension(IPAH)in NCBI database.Results Inflammatory-related genes such as CXCL9,CCL24,and SECTM1 were upregulated in both PAH rat models and IPAH patient lungs,while genes such as DGKG and DOCK9 were downregulated(P＜0.05).Pathways related to endothelial cell proliferation regulation and extracellular matrix(ECM)remodeling were significantly upregulated(P＜0.05).Conclusions The imbalance in endothelial cell proliferation and abnormal ECM remodeling may collectively contribute to PAH pathogenesis.Further exploration of these signaling pathways may provide deep in-sights for early diagnosis and targeted therapy of PAH.

Atrial fibrillation(AF)is one of the most common clinical arrhythmias and a significant risk factor for thromboembolism.The left atrial appendage(LAA)is the primary site of thrombus formation in AF patients.Recent studies have explored the mechanisms of LAA thrombosis from multiple dimensions,including anatomical structure(LAA morphology and architecture),functional indicators(hemodynamic alterations),pathophysiological mechanisms(endothelial injury,inflammatory activation),systemic diseases(renal dysfunction)and genetic factors(gene polymorphisms),providing critical evidence for precise clinical anticoagulation.This article systematically reviews the latest research advances in the mechanisms of LAA thrombosis in AF patients,aiming to offer theoretical support for the accurate assessment of thromboembolic risk and the formulation of individualized anticoagulation strategies.Additionally,it lays the foundation for exploring the intrinsic relationship and mechanisms between LAA hemodynamics and heart failure as well as thromboembolic events.

Objective:To explore the dynamic change trajectory and influencing factors of postoperative fatigue (POF) in patients with early digestive tract cancer undergoing endoscopic submucosal dissection (ESD), so as to provide theoretical basis for individualized management of such patients.Methods:Using cross-sectional survey and convenient sampling method, the patients who underwent ESD for early cancer of digestive tract in the endoscopic center of the Second Affiliated Hospital of Zhejiang University School of Medicine from January to June 2024 were selected as the research objects. The questionnaires were conducted at 30 min, 24 h, 3 days, 5 days, 7 days after ESD with Christensen's postoperative fatigue score. Spearman test was used to analyze the correlation between pain, insomnia and POF. The latent variable growth model was used to identify the potential categories of POF trajectory, and the influencing factors were analyzed by Logistic regression.Results:A total of 232 patients were finally induded, with ages of 19-94(59.53 ± 13.29) years, including 120 males and 112 femalss. The POF level of patients with early cancer of digestive tract showed a downward trend one week after operation. Three postoperative fatigue trajectories were fitted, 9.05% in moderate or severe fatigue low-speed smooth descent group (C1 group); 32.76% in moderate fatigue first decreased quickly and then slowly group (C2 group) and 58.19% in mild fatigue continuous decline group (C3 group). The result of Logistic regression analysis showed that, compared with C1 group, people without religious beliefs were morelikely to enter C2 group [ β = 1.572, OR = 4.818(1.033 - 22.465), P<0.05]; compared with C3 group, patients with high pain level and severe insomnia degree were likely to enter C1 [ β = 2.621, 0.663, OR were 13.754(2.692 - 70.283) and 1.942(1.429 - 2.638), both P<0.05] and C2 [ β = 2.010, 0.491, OR were 7.464(1.890 - 29.482) and 1.634(1.348 - 1.982), both P<0.05] group. Conclusions:There were three potential types of POF in patients with early digestive tract cancer ESD. Medical staff should pay attention to patients with severe insomnia, intense pain and religious beliefs, and give staged fatigue assessment and individualized intervention, so as to reduce the level of POF and promote rapid recovery.

Atrial fibrillation(AF)is one of the most common clinical arrhythmias and a significant risk factor for thromboembolism.The left atrial appendage(LAA)is the primary site of thrombus formation in AF patients.Recent studies have explored the mechanisms of LAA thrombosis from multiple dimensions,including anatomical structure(LAA morphology and architecture),functional indicators(hemodynamic alterations),pathophysiological mechanisms(endothelial injury,inflammatory activation),systemic diseases(renal dysfunction)and genetic factors(gene polymorphisms),providing critical evidence for precise clinical anticoagulation.This article systematically reviews the latest research advances in the mechanisms of LAA thrombosis in AF patients,aiming to offer theoretical support for the accurate assessment of thromboembolic risk and the formulation of individualized anticoagulation strategies.Additionally,it lays the foundation for exploring the intrinsic relationship and mechanisms between LAA hemodynamics and heart failure as well as thromboembolic events.

Objective:To explore the dynamic change trajectory and influencing factors of postoperative fatigue (POF) in patients with early digestive tract cancer undergoing endoscopic submucosal dissection (ESD), so as to provide theoretical basis for individualized management of such patients.Methods:Using cross-sectional survey and convenient sampling method, the patients who underwent ESD for early cancer of digestive tract in the endoscopic center of the Second Affiliated Hospital of Zhejiang University School of Medicine from January to June 2024 were selected as the research objects. The questionnaires were conducted at 30 min, 24 h, 3 days, 5 days, 7 days after ESD with Christensen's postoperative fatigue score. Spearman test was used to analyze the correlation between pain, insomnia and POF. The latent variable growth model was used to identify the potential categories of POF trajectory, and the influencing factors were analyzed by Logistic regression.Results:A total of 232 patients were finally induded, with ages of 19-94(59.53 ± 13.29) years, including 120 males and 112 femalss. The POF level of patients with early cancer of digestive tract showed a downward trend one week after operation. Three postoperative fatigue trajectories were fitted, 9.05% in moderate or severe fatigue low-speed smooth descent group (C1 group); 32.76% in moderate fatigue first decreased quickly and then slowly group (C2 group) and 58.19% in mild fatigue continuous decline group (C3 group). The result of Logistic regression analysis showed that, compared with C1 group, people without religious beliefs were morelikely to enter C2 group [ β = 1.572, OR = 4.818(1.033 - 22.465), P<0.05]; compared with C3 group, patients with high pain level and severe insomnia degree were likely to enter C1 [ β = 2.621, 0.663, OR were 13.754(2.692 - 70.283) and 1.942(1.429 - 2.638), both P<0.05] and C2 [ β = 2.010, 0.491, OR were 7.464(1.890 - 29.482) and 1.634(1.348 - 1.982), both P<0.05] group. Conclusions:There were three potential types of POF in patients with early digestive tract cancer ESD. Medical staff should pay attention to patients with severe insomnia, intense pain and religious beliefs, and give staged fatigue assessment and individualized intervention, so as to reduce the level of POF and promote rapid recovery.

Objective:To observe the effects of transcranial direct current stimulation (tDCS) on functional connectivity (FC) in language-related brain regions of patients with picture-naming dysfunction after cerebral infarction by using resting state functional magnetic resonance imaging(rs-fMRI).Methods:Twenty-eight patients with post-infarction picture-naming dysfunction were divided into an acute stage group( n=16) and a recovery stage group( n=12) according to the course of the disease, and 18 middle-aged and elderly volunteers were recruited as the normal control group.The anodic tDCS was applied on the posterior perisylvian region(PPR) of the left sylvian of the patients, 5 days a week for 2 weeks.Before and after the 2 weeks′ treatment, the rs-fMRI and Psycholinguistic Assessment of Chinese Aphasia (PACA)-picture-naming subscale were performed, and FC changes in language-related brain areas were observed. Results:After treatment, the PACA scores of patients in both acute and recovery stage groups were significantly improved after treatment( P<0.05). Compared with normal subjects, FC in multiple brain regions and particularly the Wernicke area was reduced in both cerebral hemispheres among the patient group. It was more severe in the dominant hemisphere.After the tDCS treatment, FC in both frontotemporal lobes and in the Wernicke area was significantly enhanced in both the acute and recovery groups. Further comparison showed that in the acute group FC in both temporo-occipital lobes was significantly enhanced after treatment. In the recovery group, the enhanced FC in the left temporal lobe before the treatment was significantly reduced after treatment. Conclusion:The fMRI technique can evaluate changes in brain connectivity in aphasia patients with picture-naming dysfunction after cerebral infarction accurately and non-invasively.tDCS may improve picture-naming function of stroke patients by enhancing the FC in bilateral language-related brain areas(concentrated in frontotemporal lobes) and Wernicke area.

Experiential teaching is a practical, reflective, and situational teaching method. Based on the systematic review of literature published worldwide, this paper summarizes the characteristics and organizational forms of experiential teaching, with a focus on its current application and existing problems in teaching geriatric nursing. This review provides suggestions for the reform of teaching methods of geriatric nursing in China.

Objective The objective of this study was to provide methodological references for the inheritance of the experience of well-known Chinese medicine doctors in the treatment of kidney disease.Methods The study collected medical case data for IgA nephropathy,diagnosed and treated by Professor Yang Nizhi's outpatient department at Guangdong Provincial Hospital of Traditional Chinese Medicine from 2010 to 2020.The data was standardized and divided into three groups:urine and blood,urine turbidity,and renal failure groups.The study utilized the FangNet platform to apply the PageRank algorithm and calculate the THScore of different subgroups of core herbs for IgA nephropathy.The distribution pattern of syndrome differentiation and corresponding herb use regulations were visualized through Python(SciPy package,Clusterheatmap package),and the study explored and verified the drug prescription through exploratory and confirmatory factor analysis based on Pearson correlation coefficient.The weighted least squares estimation mean and variance adjusted(WLSMV)and the oblique rotated GEOMIN method were used with the Mplus software.Results The study included a total of 548 treatments for 145 patients with IgA nephropathy,with heamturia group(54 cases),urine turbidity group(51 cases),and renal failure group(40 cases).Results showed 9 basic syndromes such as Qi deficiency syndrome(91.79%),blood stasis syndrome(77.01%),damp-heat syndrome(66.06%),and Yin deficiency syndrome(38.69%).There are 24 core drugs in total,23 in the urine and blood group,21 in the urine turbidity group,and 16 in the renal failure group.These drugs mainly include qi-tonifying and yang-invigorating drugs,nourishing yin and blood drugs,promoting blood circulation and removing blood stasis drugs,and clearing heat and cooling blood drugs.The regulations for the differentiation and medication of IgA nephropathy(Z-Score>0.5 and P<0.05)were as follows:Huangqi,Shan Zhu Yu,and Tusizi were commonly used in Qi deficiency syndrome;Danshen,Ze Lan,and Shan Zhu Yu were commonly used in blood stasis syndrome;Pu Gong Ying,Shi Wei,Tao Ren,and Tu Fu Ling were commonly used in damp-heat syndrome;and Mo Han Lian,Tai Zi Shen,and Nv Zhen Zi were commonly used in Yin deficiency syndrome.Through exploratory and confirmatory factor analysis,the core drug combination factors for the treatment of IgA nephropathy by Professor Yang Nizhi were obtained as follows:F1(Tusizi,Shan Zhu Yu,Huangqi);F2(White Mao Gen,Xiao Ji,Qian Cao);F3(Nv Zhen Zi,Mo Han Lian,Tai Zi Shen);and F4(Ze Lan,Tao Ren).Conclusion This study analyzed the diagnosis and treatment experience of Professor Yang Nizhi in the treatment of IgA nephropathy by grouping,defining the core syndrome of"Qi deficiency and blood stasis,damp-heat and Yin deficiency",and the core treatment methods of"tonifying Qi,promoting blood circulation,clearing heat,and nourishing Yin"using the PageRank algorithm and Mplus factor analysis.The study provided methodological references for the inheritance of the experience of famous Chinese medicine doctors and promoted the development and utilization of traditional Chinese medicine.