Laboratory animals are essential in scientific research and experimental teaching in colleges and universities. Disciplines such as life sciences, medicine, pharmacy, chemistry, and biomedical engineering heavily rely on animal experiments. The standardized barrier environmental facility for laboratory animals provides a fundamental platform for stable, scientific, and reliable animal experiment results. Rigorous access management for such facilities is a vital safeguard for maintaining standardized operations of facilities, controlling the quality and stability of laboratory animals, mitigating pathogen contamination risks among animals and laboratory staff, and preventing biosecurity incidents such as zoonotic disease outbreaks. Taking the small-scale barrier facilities for laboratory rats and mice at Nanjing University's Xianlin Campus, operational since 2019, as an example, this study focuses on the safety access management system of these facilities. Based on five years of operational data and accumulated experience in studying and optimizing the access management system, this study, from the perspectives of management system development and the formulation and implementation of standard operating procedures, reviews five aspects of access management: personnel access, animals access, material access, equipment access, and air circulation control. Furthermore, these aspects are systematically analyzed and summarized to serve as a reference for the construction and management of the laboratory animal facilities in universities, while also contributing to scientific research, public health security, and the well-being of experimental personnel.

Brain organoids are three-dimensional (3D) neural cultures that self-organize from pluripotent stem cells (PSCs) cultured in vitro. Compared with traditional two-dimensional (2D) neural cell culture systems, brain organoids demonstrate a significantly enhanced capacity to faithfully replicate key aspects of the human brain, including cellular diversity, 3D tissue architecture, and functional neural network activity. Importantly, they also overcome the inherent limitations of animal models, which often differ from human biology in terms of genetic background and brain structure. Owing to these advantages, brain organoids have emerged as a powerful tool for recapitulating human-specific developmental processes, disease mechanisms, and pharmacological responses, thereby providing an indispensable model for advancing our understanding of human brain development and neurological disorders. Despite their considerable potential, conventional brain organoids face a critical limitation: the absence of a functional vascular system. This deficiency results in inadequate oxygen and nutrient delivery to the core regions of the organoid, ultimately constraining long-term viability and functional maturation. Moreover, the lack of early neurovascular interactions prevents these models from fully recapitulating the human brain microenvironment. In recent years, the introduction of vascularization strategies has significantly enhanced the physiological relevance of brain organoid models. Researchers have successfully developed various vascularized brain organoid models through multiple innovative approaches. Biological methods, for example, involve co-culturing brain organoids with endothelial cells to induce the formation of static vascular networks. Alternatively, co-differentiation strategies direct both mesodermal and ectodermal lineages to generate vascularized tissues, while fusion techniques combine pre-formed vascular organoids with brain organoids. Beyond biological approaches, tissue engineering techniques have played a pivotal role in promoting vascularization. Microfluidic systems enable the creation of dynamic, perfusable vascular networks that mimic blood flow, while 3D printing technologies allow for the precise fabrication of artificial vascular scaffolds tailored to the organoid’s architecture. Additionally, in vivo transplantation strategies facilitate the formation of functional, blood-perfused vascular networks through host-derived vascular infiltration. The incorporation of vascularization has yielded multiple benefits for brain organoid models. It alleviates hypoxia within the organoid core, thereby improving cell survival and supporting long-term culture and maturation. Furthermore, vascularized organoids recapitulate critical features of the neurovascular unit, including the early structural and functional characteristics of the blood-brain barrier. These advancements have established vascularized brain organoids as a highly relevant platform for studying neurovascular disorders, drug screening, and other applications. However, achieving sustained, long-term functional perfusion while preserving vascular structural integrity and promoting vascular maturation remains a major challenge in the field. In this review, we systematically outline the key stages of human neurovascular development and provide a comprehensive analysis of the various strategies employed to construct vascularized brain organoids. We further present a detailed comparative assessment of different vascularization techniques, highlighting their respective strengths and limitations. Additionally, we summarize the principal challenges currently faced in brain organoid vascularization and discuss the specific technical obstacles that persist. Finally, in the outlook section, we elaborate on the promising applications of vascularized brain organoids in disease modeling and drug testing, address the main controversies and unresolved questions in the field, and propose potential directions for future research.

Objective To investigate the size variation in the first metatarsal of extant primates.Methods In this study,we analyzed 135 first metatarsal specimens across 12 primate genera,quantifying eight linear measurements,articular surface areas,mid-shaft cross-sectional area,total surface area,volume,and derived indices.Multivariate patterns were assessed through mean-based correspondence analysis and principal component analysis(PCA).Results Eulemur,Otolemur,Cebus,and Perodicticus exhibited a relatively high metatarsal surface-area-to-volume ratio.Perodicticus additionally showed a low articular facet index.Propithecus,Colobus,and Macaca displayed lower values for metatarsal shaft robusticity,the ratio of shaft cross-sectional area to base articular surface area,and the proximal articular facet index.Nasalis possessed a relatively high articular facet index.Pongo,Pan,Gorilla,and Homo sapiens were characterized by higher metatarsal shaft robusticity and a lower metatarsal surface-area-to-volume ratio.Principal component analysis revealed that the 12 extant primate genera could be broadly divided into two groups.Group 1 comprised Pongo,Pan,Gorilla and H.sapiens,although H.sapiens formed a distinct cluster relative to the extant great apes.Group 2 included Eulemur,Otolemur,Perodicticus,Propithecus,Cebus,Colobus,Macaca and Nasalis.Conclusion The relative sizedistribution of the first metatarsal provides some reference value for classifying extant primates.However,it demonstrates no clear correlations with specific locomotor patterns or foot grasping ability.

Psoriasis is a chronic inflammatory skin disease, and its pathogenesis is largely modulated by abnormal angiogenesis. Previous research has indicated that AlkB homolog 5 (ALKBH5), an important demethylase affecting N⁶-methyladenosine (m⁶A) modification, plays a role in regulating angiogenesis in cardiovascular and eye diseases. Our present study found that ALKBH5 was upregulated and co-localized with cluster of differentiation 31 (CD31) in the skin of IMQ group compared with control group. ALKBH5-deficient mice decreased IMQ-induced psoriatic dermatitis and exhibited histological improvements, including decreased epidermal thickness, hyperkeratosis, numbers of dermal capillary vessels and inflammatory cell infiltration. ALKBH5-KO mice alleviated angiogenesis in psoriatic lesions by downregulating the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Additionally, the expression of ALKBH5 was significantly upregulated in IL-17A-induced human umbilical vein endothelial cells (HUVECs), which further promoted the expression of angiogenesis-related cytokines and endothelial cell proliferation. Cell proliferation and angiogenesis were suppressed in ALKBH5 knockdown group, whereas ALKBH5 overexpression promoted these processes. The regulation of angiogenesis in HUVECs by ALKBH5 was facilitated through the AKT-mTOR pathway. Collectively, ALKBH5 plays a pivotal role in psoriatic dermatitis and angiogenesis, which may offer a new potential targets for treating psoriasis.
Animals ; Psoriasis/chemically induced* ; Mice ; Humans ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; AlkB Homolog 5, RNA Demethylase/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Cell Proliferation ; Mice, Knockout ; Disease Models, Animal ; Signal Transduction ; Male ; Skin/blood supply* ; Mice, Inbred C57BL ; Angiogenesis

Objective:To explore the impact of postoperative extracorporeal membrane oxygenation (ECMO) support on neurodevelopment of neonatal patients with complex congenital heart disease (CHD) and its early neurorehabilitation intervention effect.Methods:A retrospective analysis was performed; 17 neonates who underwent complex CHD corrective surgery with ECMO support in Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University from January 1, 2019 to December 31, 2021 were chosen. Neurological injury of the neonates was observed during ECMO support period. At 12 months old, the neonates underwent head MRI; and Griffiths Developmental Scale-Chinese version (GDS-C) were performed on the neonates to evaluate the neurodevelopment. A systematic neurorehabilitation intervention program was implemented for neonates with abnormal neurodevelopment as indicated by GDS-C, and GDS-C was performed again to assess the neurodevelopmental changes of the neonates at 36 months old.Results:(1) During ECMO support period, 13 neonates (76.47%) suffered from neurological damage, including 8 with simple intracranial hemorrhage, 2 with intracranial hemorrhage combined with ischemic hypoxic changes, 1 with intracranial hemorrhage combined with white matter injury, and 2 with white matter injury. (2) At 12 months old, head MRI revealed hemorrhagic foci or softening foci in 2 neonates; GDS-C indicated 12 neonates with delayed neurodevelopment, 4 with borderline status, and only 1 with normal development. (3) Among the 16 neonates with abnormal neurodevelopment who received systematic neurorehabilitation, 11 achieved normal neurodevelopment, 4 remained borderline, and 1 still had delayed development at 36 months old indicated by GDS-C. Compared with those before the neurorehabilitation intervention, the neonates after neuro-rehabilitation intervention had better neurodevelopmental rating (average ranks: 9.630 and 23.380, respectively), and significantly improved neurodevelopmental quotients in the 4 major dimensions of motor, personal-social, language, and hand-eye coordination ( P<0.05). Conclusion:Neonates accepted CHD surgery face high risks of postoperative neurological complications during ECMO support period; incidence of neurodevelopmental abnormalities is high in neonates at 12 months old; by implementing a systematic neurorehabilitation intervention, the outcomes of neonates with neurodevelopmental abnormalities can be effectively improved.

Objective To investigate the status of hearing impaired children's hearing device independence skills,and to explore the ways to improve their self-use of hearing equipment.Methods This study surveyed 64 re-habilitation teachers and 411 parents of children with hearing impairment aged 0-12 years.Through face-to-face or remote telephone interview,3 good habits(A asking parents for advice before removing the HA,B putting the de-vice into a moisture-proof box after removing it,C bringing batteries to school and knowing where are them)and 3 key abilities[D wearing the device independently,E replacing the battery independently,and F independently handle foreign bodies in the ear mold(Fa)and water vapor(Fb)]was investigated.The age when mastering skills or de-veloping habits difference of hearing impaired children in different groups were compared.Results ① The ratio of ability D in the bilateral CI group and the bilateral HA group of preschool children was 30.97％and 18.57％respec-tively.Among elementary school children,85.29％and 90.70％had this ability respectively.② The ratio of ability E in the bilateral CI group,the bilateral HA group and the bimodel group were 11.50％,15.71％and 16.49％,re-spectively.Among elementary school children,64.71％,53.49％and 68.52％had this ability,respectively.③Among preschool children,there was no statistical difference in age when different equipment groups developed the three good habits and acquired ability D and E(P＞0.05).④ Among primary school children,there was a statisti-cal difference in the age when different equipment groups formed habit A(P＜0.05),and the age when double CI group had this ability was slightly earlier than the double HA group.There was no significant difference in other abilities among age groups(P＞0.05).Conclusion The age at which hearing impaired children develop the three good habits precedes the age at which they master the key skills,which accords with the law of skill acquisition and development of ordinary children.Corresponding teaching process should be based on the age and ability of hearing-impaired children without considering the type of equipment.

Objective:To analyze the evaluation value of contrast-enhanced ultrasound (CEUS) combined with automatic volumetric ultrasound in the efficacy of neoadjuvant chemotherapy (NAC) for breast cancer.Methods:A retrospective study was conducted on 98 female patients with breast cancer admitted to Shaanxi Provincial Cancer Hospital from January to December 2022. All patients received 4 cycles of NAC, and underwent conventional ultrasound, automatic volumetric ultrasound, CEUS, and histopathological examination before and after treatment. Based on the post-treatment histopathological efficacy, patients were divided into the effective group ( n=67) and the ineffective group ( n=31). The CEUS and automatic volumetric ultrasound parameters before and after treatment, as well as the evaluation efficacy of these two types of parameters for NAC efficacy in breast cancer, were compared. The value of CEUS combined with automatic volumetric ultrasound in evaluating NAC efficacy for breast cancer was analyzed. Results:After NAC treatment, the CEUS parameters [time to peak (TTP) and arrival time (AT) of contrast agent] were longer than those before treatment, while the peak intensity (PI) was lower than that before treatment (all P<0.05); the automatic volumetric ultrasound parameters (tumor volume, area, thickness, length, and width) after NAC treatment were all smaller than those before treatment (all P<0.05). After treatment, the PI, volume, area, thickness, length, and width in the effective group were significantly smaller than those in the ineffective group, while the TTP and AT were significantly longer than those in the ineffective group (all P<0.05). Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) of CEUS parameters and automatic volumetric ultrasound parameters for predicting effective NAC efficacy in breast cancer was 0.837(0.749-0.904) and 0.864(0.780-0.925), respectively, with no statistically significant difference between the two ( P=0.674). The AUC of the combined parameters for predicting effective NAC efficacy was 0.942(0.875-0.979), which was significantly higher than that of CEUS parameters or automatic volumetric ultrasound parameters alone ( Z=2.947, 2.135, P=0.003, 0.033). Conclusions:The combination of CEUS and automatic volumetric ultrasound parameters has high value in the efficacy evaluation of NAC for breast cancer and can be used as a clinical reference.

Objective To investigate the relationship between the serum levels of lncRNA mathematically expressed gene 3(lncRNA MEG3),lncRNA SRY-box transcription factor 2 overlapping transcript(lncRNA SOX2OT)and renal function and prognosis in patients with type 2 diabetic nephropathy(T2DN).Methods 205 patients with T2DN admitted to Shaanxi Provincial People's Hospital from January 2019 to January 2021(T2DN group)were selected,as well as 150 simple T2DM patients(T2DM group)and 150 healthy individuals(control group)during the same period.And the patients with T2DN were classified into the poor prognosis group(n=73)and the good prognosis group(n=132)according to the 3-year prognosis.Serum levels of lncRNA MEG3 and lncRNA SOX2OT were detected.Pearson analysis was used for correlation analysis;The influencing factors were analyzed using logistic regression,and the predictive value was evaluated using the subject's work characteristic curve.Results The serum lncRNA MEG3(2.20±0.32)in the T2DN group was higher than that in the T2DM group(1.49±0.20)and control group(1.00±0.06),and the lncRNA SOX2OT(0.50±0.11)was lower than that in the T2DM group(0.73±0.15)and control group(1.05±0.16),the differences were statistically significant(t=23.960,45.322;28.745,16.670,all P<0.01).The serum lncRNA MEG3 levels in T2DN patients were negatively correlated with estimated glomerular filtration rate(eGFR)and positively correlated with urinary albumin/creatinine ratio(UACR)levels(r=-0.532,0.485,all P<0.01)and the serum lncRNA SOX2OT level was positively correlated with eGFR and negatively correlated with UACR(r=0.421,-0.517,all P<0.01).The risk factors for poor prognosis in T2DN patients were chronic kidney disease stage 4,UACR and lncRNA MEG3(Wald χ2=6.360,6.678,16.652,all P＜0.05)while the protective factors were eGFR,lncRNA SOX2OT(Wald χ2=5.463,11.797,all P＜0.05).The AUC predicted by the combination of serum lncRNA MEG3 and lncRNA SOX2OT was larger than that predicted by lncRNA MEG3 and lncRNA SOX2OT predicts separately,and the differences were statistically significant(Z=3.841,3.337,all P<0.05).Conclusion Elevated serum lncRNA MEG3 levels and reduced lncRNA SOX2OT levels are associated with reduced renal function and poor prognosis in patients with T2DN,and the combination of the two tests has a high predictive value for poor prognosis in patients with T2DN.

In 2040, neurodegenerative diseases (NDD) will overtake cancer as the second leading cause of death after cardiovascular and cerebrovascular diseases. Therefore, the search for effective intervention measures has become the top priority to deal with this difficult burden. Hyperbaric oxygen therapy (HBOT) has been used for the past 50 years to treat conditions such as decompression sickness, carbon monoxide poisoning and radiation damage. In recent years, studies have confirmed that HBOT has good effects in improving cognitive impairment after brain injury and stroke, and alleviating neurodegeneration and dysfunction related to NDD. Here we reviewed the pathogenesis and treatment state of NDD, introduced the application of HBOT in animal models and clinical studies of NDD, and expounded the application potential of HBOT in the treatment of NDD from the perspective of mitochondrial function, neuroinflammation, neurogenesis and angiogenesis, oxidative stress, apoptosis, microcirculation and epigenetics.
Hyperbaric Oxygenation ; Humans ; Neurodegenerative Diseases/physiopathology* ; Animals ; Oxidative Stress ; Apoptosis ; Mitochondria/physiology* ; Neurogenesis ; Epigenesis, Genetic

This study aims to comprehensively analyze the material basis of toad visceral oil(hereafter referred to as toad oil), and explore the pharmacological effect of toad oil on atopic dermatitis(AD). Ultra-high performance liquid chromatography-linear ion trap/orbitrap high-resolution mass spectrometry(UHPLC-LTQ-Orbitrap-MS) and gas chromatography-mass spectrometry(GC-MS) were employed to comprehensively identify the chemical components in toad oil. The animal model of AD was prepared by the hapten stimulation method. The modeled animals were respectively administrated with positive drug(0.1% hydrocortisone butyrate cream) and low-and high-doses(1%, 10%) of toad oil by gavage. The effect of toad oil on AD was evaluated with the AD score, ear swelling rate, spleen index, and pathological section results as indicators. A total of 99 components were identified by UHPLC-LTQ-Orbitrap-MS, including 14 bufadienolides, 7 fatty acids, 6 alkaloids, 10 ketones, 18 amides, and other compounds. After methylation of toad oil samples, a total of 20 compounds were identified by GC-MS. Compared with the model group, the low-and high-dose toad oil groups showed declined AD score, ear swelling rate, and spleen index, alleviated skin lesions, and reduced infiltrating mast cells. This study comprehensively analyzes the chemical composition and clarifies the material basis of toad oil. Meanwhile, this study proves that toad oil has a good therapeutic effect on AD and is a reserve resource of traditional Chinese medicine for external use in the treatment of AD.
Animals ; Dermatitis, Atopic/immunology* ; Disease Models, Animal ; Mice ; Male ; Gas Chromatography-Mass Spectrometry ; Humans ; Bufonidae ; Oils/administration & dosage* ; Chromatography, High Pressure Liquid ; Female ; Mice, Inbred BALB C