PHLDA1-PRDM1 mediates the effect of lentiviral vectors on fate-determination of human retinal progenitor cells.

Lentiviral vectors have markedly enhanced gene therapy efficiency in treating congenital diseases, but their long-term safety remains controversial. Most gene therapies for congenital eye diseases need to be carried out at early ages, yet the assessment of related risks to ocular development posed by lentiviral vectors is challenging. Utilizing single-cell transcriptomic profiling on human retinal organoids, this study explored the impact of lentiviral vectors on the retinal development and found that lentiviral vectors can cause retinal precursor cells to shift toward photoreceptor fate through the up-regulation of key fate-determining genes such as PRDM1. Further investigation demonstrated that the intron and intergenic region of PRDM1 was bound by PHLDA1, which was also up-regulated by lentiviral vectors exposure. Importantly, knockdown of PHLDA1 successfully suppressed the lentivirus-induced differentiation bias of photoreceptor cells. The findings also suggest that while lentiviral vectors may disrupt the fate determination of retinal precursor cells, posing risks in early-stage retinal gene therapy, these risks could potentially be reduced by inhibiting the PHLDA1-PRDM1 axis.

Stratified Nursing Based on ICNSS Score: Study on the Impact of Complications and Rehabilitation Effects in Patients with Acute Myocardial Infarction Complicated by Heart Failure.

Objective: To analyze the application effects of stratified nursing based on the ICNSS score and its influence on complications and rehabilitation effects in patients with Acute Myocardial Infarction (AMI) complicated by Heart Failure (HF). Methods: A retrospective analysis was conducted on clinical data of 97 patients with AMI complicated by HF admitted to Xingtai Central Hospital between January 2021 and January 2023. All patients met the inclusion and exclusion criteria. Patients were divided into a control group (n=47) and an observation group (n=50) based on different nursing interventions received. The control group received routine nursing interventions, while the observation group received stratified nursing interventions based on the ICNSS score. The comparison between the two groups involved Cardio Care Unit (CCU) treatment duration, psychological status Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), cardiac function indicators Creatine Kinase (CK), Left Ventricular End-Diastolic Diameter (LVEDD), Left Ventricular Ejection Fraction (LVEF), Cardiac Output (CO), quality of life (SF-36), occurrence of nursing complications, and nursing satisfaction. Results: 1. CCU treatment duration and psychological status: After treatment, the SAS and SDS scores and CCU treatment duration in the observation group were significantly lower than those in the control group (P < .05). 2. Cardiac function indicators: After treatment, the CK and LVEDD levels in the observation group were significantly higher than those in the control group, while LVEF and CO levels were significantly lower than those in the control group (P < .05). 3. Quality of life: After treatment, the physiological function, physical function, mental status, and social relationship scores in the observation group were significantly higher than those in the control group (P < .05). 4. Occurrence of nursing complications: The occurrence rate of nursing complications in the control group was 17.02%, while in the observation group, it was 2.00%, significantly lower than that in the control group (P < .05). 5. Nursing satisfaction: The nursing satisfaction in the control group was 78.72%, whereas in the observation group, it was 94.00%, significantly higher than that in the control group (P < .05). Conclusion: Stratified nursing based on the ICNSS score demonstrates significant application effects in patients with AMI complicated by HF. Compared to routine nursing interventions, stratified nursing based on the ICNSS score further reduces CCU treatment duration, alleviates negative psychological emotions, improves cardiac function, and effectively controls and reduces the risk of complications. Moreover, this approach significantly enhances nursing satisfaction for both patients and their families, contributing significantly to promoting harmony in doctor-patient relationships, and deserves clinical promotion and application.

Genetic landscape and autoimmunity of monocytes in developing Vogt-Koyanagi-Harada disease.

Vogt-Koyanagi-Harada (VKH) disease is a systemic autoimmune disorder affecting multiple organs, including eyes, skin, and central nervous system. It is known that monocytes significantly contribute to the development of autoimmune disease. However, the subset heterogeneity with unique functions and signatures in human circulating monocytes and the identity of disease-specific monocytic populations remain largely unknown. Here, we employed an advanced single-cell RNA sequencing technology to systematically analyze 11,259 human circulating monocytes and genetically defined their subpopulations. We constructed a precise atlas of human blood monocytes, identified six subpopulations-including S100A12, HLA, CD16, proinflammatory, megakaryocyte-like, and NK-like monocyte subsets-and uncovered two previously unidentified subsets: HLA and megakaryocyte-like monocyte subsets. Relative to healthy individuals, cellular composition, gene expression signatures, and activation states were markedly alternated in VKH patients utilizing cell type-specific programs, especially the CD16 and proinflammatory monocyte subpopulations. Notably, we discovered a disease-relevant subgroup, proinflammatory monocytes, which showed a discriminative gene expression signature indicative of inflammation, antiviral activity, and pathologic activation, and converted into a pathologic activation state implicating the active inflammation during VKH disease. Additionally, we found the cell type-specific transcriptional signature of proinflammatory monocytes, ISG15, whose production might reflect the treatment response. Taken together, in this study, we present discoveries on accurate classification, molecular markers, and signaling pathways for VKH disease-associated monocytes. Therapeutically targeting this proinflammatory monocyte subpopulation would provide an attractive approach for treating VKH, as well as other autoimmune diseases.

Review of Atom Chips for Absolute Gravity Sensors.

As a powerful tool in scientific research and industrial technologies, the cold atom absolute gravity sensor (CAGS) based on cold atom interferometry has been proven to be the most promising new generation high-precision absolute gravity sensor. However, large size, heavy weight, and high-power consumption are still the main restriction factors of CAGS being applied for practical applications on mobile platforms. Combined with cold atom chips, it is possible to drastically reduce the complexity, weight, and size of CAGS. In this review, we started from the basic theory of atom chips to chart a clear development path to related technologies. Several related technologies including micro-magnetic traps, micro magneto-optical traps, material selection, fabrication, and packaging methods have been discussed. This review gives an overview of the current developments in a variety of cold atom chips, and some actual CAGS systems based on atom chips are also discussed. We summarize by listing some of the challenges and possible directions for further development in this area.

Tunable terahertz electromagnetically induced transparency based on a composite structure superconducting metamaterial.

We experimentally present a tunable electromagnetically induced transparency (EIT)-like response in bright-bright mode resonators. In contrast to previous studies, we used NbN film and a gold film composite structure metamaterial. A significant slow-light effect could be observed at the transmission window, and the maximum group index could reach 100. As a variation in temperature alters the intrinsic ohmic loss of superconducting NbN film, a temperature-dependent transmittance and slow-light effect were observed. To better illustrate the physical mechanism of the two modes, a hybrid coupling model was introduced to fit the experimental transmission spectra and extract the characteristic parameters of sub-resonators. We found excellent agreement with experimental results. Our results provide deeper insight into the metamaterial analogs of an EIT-like response and offer an alternative approach for engineering slow-light devices, bandpass filters, and switches/modulators at terahertz frequencies.

Accuracy of the trough position in expansive open-door cervical laminoplasty using computer navigation techniques: a single-centre retrospective study.

PURPOSE: This study aims to assess whether computer navigation can improve the accuracy of the trough position and clinical outcomes of expansive open-door cervical laminoplasty (EOLP). METHODS: We reviewed a single centre of 28 conventional EOLP and 24 computer navigation EOLP cases. The conventional group had 102 laminae while the navigation group had 88. The distance from the medial cortex to the pedicle on the open-door side (OD) and hinge side (HD) was measured. Furthermore, the area of the spinal canal corresponding to each lamina before and after the surgical procedure was also measured. We then compared the differences in radiographic parameters and clinical outcomes between the two groups. RESULTS: OD and HD were smaller in the navigation group compared to the conventional group, and the enlarged area of the spinal canal was larger in the navigation group than in the conventional group. The Japanese Orthopaedic Association (JOA) scores one year after the surgical procedure improved in both groups compared to the pre-operative period, and the JOA recovery rate was higher in the navigation group. The incidence of hinge fracture was lower in the navigation group, and the incidence of C5 palsy and axial pain was not statistically different between the two groups. CONCLUSION: The use of computer navigation techniques has the potential to significantly improve the accuracy of EOLP compared to conventional procedures. It has been shown to more fully expand the spinal canal and contribute to clinical efficacy.

Correlation Between Lifestyle Patterns and Cognitive Function Among Community-Dwelling Older Chinese Adults in the Pre-Dementia Stages: A Latent Class Analysis.

Lifestyle activity engagement is a modifiable factor for cognitive decline. We aimed to identify lifestyle patterns (LPs) among community-dwelling older adults in the pre-dementia stages and to explore the links between LPs, cognitive function, and individual characteristics. 702 older Chinese adults were recruited. Three LPs were identified by latent class analysis: active aging lifestyle pattern (AALP), leisure lifestyle pattern (LLP), and work-centered lifestyle pattern (WLP). AALP refers to participation in various activities that are meaningful to individuals and benefit their well-being. LLP is the pattern of activities aimed at recreation. WLP refers to the LP where individuals are most likely to engage in work-related activities. However, only AALP is protected against mild cognitive impairment (MCI). Multinomial logistic regression models revealed the differences in individual characteristics among participants with different LPs, indicating the importance of tailored intervention strategies. As a protective factor against MCI, AALP should be highlighted in community-based care.

Comparative single-cell transcriptomic analysis across tissues of aging primates reveals specific autologous activation of ZNF281 to mitigate oxidative stress in cornea.

Reactive oxygen species (ROS) and oxidative stress accelerate cellular aging, but their impact on different tissues varies. The cornea, known for its robust antioxidant defense systems, is relatively resistant to age-related diseases like cancer. However, the precise mechanisms by which the cornea maintains ROS homeostasis during aging remain unclear. Through comparative single-cell transcriptomic analysis of the cornea and other tissues in young and old nonhuman primates, we identified that a ZNF281 coding transcriptomic program is specifically activated in cornea during aging. Further investigation revealed that ZNF281 forms a positive feedback loop with FOXO3 to sense elevated levels of ROS and mitigate their effects potentially by regulating the mitochondrial respiratory chain and superoxide dismutase (SOD) expression. Importantly, we observed that overexpression of ZNF281 in MSCs prevented cellular senescence. In summary, these findings open up possibilities for understanding tissue-specific aging and developing new therapies targeting ROS damage.

Simultaneous profiling of RNA isoforms and chromatin accessibility of single cells of human retinal organoids.

Single-cell multi-omics sequencing is a powerful approach to analyze complex mechanisms underlying neuronal development and regeneration. However, current methods lack the ability to simultaneously profile RNA alternative splicing and chromatin accessibility at the single-cell level. We develop a technique, single-cell RNA isoform and chromatin accessibility sequencing (scRICA-seq), which demonstrates higher sensitivity and cost-effectiveness compared to existing methods. scRICA-seq can profile both isoforms and chromatin accessibility for up to 10,000 single cells in a single run. Applying this method to human retinal organoids, we construct a multi-omic cell atlas and reveal associations between chromatin accessibility, isoform expression of fate-determining factors, and alternative splicing events in their binding sites. This study provides insights into integrating epigenetics, transcription, and RNA splicing to elucidate the mechanisms underlying retinal neuronal development and fate determination.

Spinal intradural extramedullary tumors: microscopic keyhole resection with the focus on intraoperative neurophysiological monitoring and long-term outcome.

OBJECTIVE: Spinal schwannomas (SS) and spinal meningiomas (SM) account for most intradural extramedullary (IDEM) tumors. These tumors are usually benign lesions, which generally respond favorably to surgical excision. Few studies up to now tried to determine the long-term outcome after minimally invasive surgery (MIS) with multimodal intraoperative neurophysiological monitoring (IONM) for IDEM tumors. The aim of this study was to present one of the largest case series with special regard to IONM findings and long-term outcome after MIS-keyhole surgery with a tubular retractor system. METHODS: Between January 2013 and August 2018, 87 patients with IDEM tumors who underwent tumor removal surgery via MIS-keyhole approach under multimodal IONM were retrospectively reviewed. The neurological status was assessed using a modified McCormick grading scale pre- and postoperatively. Multimodal IONM consisted of motor evoked potentials (MEP), somatosensory evoked potentials (SEP), and electromyography (EMG). Both short-term and long-term clinical evaluations as well as patients' medical files were retrospectively analyzed. RESULTS: Surgeries were performed for resection of SS in 49 patients and SM in 38 patients. Tumor locations were cervical in 16.1%, thoracic in 48.3%, thoracolumbar in 4.6%, lumbar 31%. Critical IONM changes were detected in 9 operations (10.3%) in which there were 2 SEPs, 5 MEPs, and 2 EMG events. Three IONM changes (2 MEPs, 1 EMG) were turned out to be transient change in nature since they were resolved in a short time when immediate corrective actions were initiated. Six patients with permanent IONM changes (2SEPs, 3MEPs, 1EMG event), all deficits had resolved during hospitalization or on short -term follow-up evaluation. Sensitivity, specificity, and positive and negative predicted values of IONM were 100, 96, 67, and 100%, respectively. Gross total resection rate was 100%, and a stable or improved McCormick grade exhibited in all patients. No tumor recurrence and no spinal instability were found in the long-term follow-up evaluation (mean 5.2 ± 2.9 years postoperatively). Overall, 94% of patients were either satisfied or very satisfied with their operation, and 93% patients reported excellent or good general clinical outcome according to Odom's criteria. CONCLUSION: MIS-keyhole surgery with multimodal IONM for IDEM tumors enables a high level of satisfaction and a satisfying long-term clinical and surgical outcome.

Avatrombopag for the treatment of thrombocytopenia in children's patients following allogeneic hematopoietic stem-cell transplantation: A pilot study.

Thrombocytopenia following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a common and life-threatening complication. Thus, new prevention and treatment strategies for post-HSCT thrombocytopenia are urgently required. In recent studies, thrombopoietin receptor agonists (TPO-RA) for treating post-HSCT thrombocytopenia indicated efficiency and safety. The improved effect of post-HSCT thrombocytopenia in adults was found in the administration of avatrombopag which was a new TPO-RA. However, there was no relevant study in the children's cohort. Herein, we retrospectively analyzed the effect of avatrombopag in post-HSCT thrombocytopenia in children. As a result, the overall response rate (ORR) and complete response rate (CRR) were 91% and 78%, respectively. Furthermore, both cumulative ORR and CRR were significantly lower in the poor graft function (PGF)/secondary failure of platelet recovery (SFPR) group compared to the engraftment-promotion group (86.7% vs. 100%, p = 0.002 and 65.0% vs. 100%, p < 0.001, respectively). Achieving OR required a median of 16 days in the PGF/SFPR group while 7 days in the engraftment-promotion group (p = 0.003). Grade III-IV acute graft vs. host disease and inadequate megakaryocytes were identified as risk factors of CRR only in univariate analysis (p = 0.03 and p = 0.01, respectively). No severe adverse events were documented. Conclusively, avatrombopag is an alternatively efficient and safe agent for treating post-HSCT thrombocytopenia in children.

Applying Rituximab During the Conditioning Regimen Prevents Epstein-Barr Virus Infection Following Allogeneic Hematopoietic Stem Cell Transplant in a Children's Cohort: A Retrospective Case-Control Study.

INTRODUCTION: Since hematopoietic stem cell transplant (HSCT) is an important therapy for malignant and non-malignant pediatric diseases, improving transplant-related mortality remains a challenge. Currently, rituximab, a monoclonal antibody of anti-CD20, is widely used for several post-HSCT complications. However, few studies have focused on the application of rituximab before HSCT. METHODS: We conducted a retrospective case-control study from January 2019 to July 2021 to determine this effect in a single center. Forty-eight patients were included in the rituximab group, with a one-to-one ratio matched to the control group. RESULTS: Both the occurrence rate and cumulative incidence rate of Epstein-Barr virus (EBV) infection were significantly lower in the rituximab group than in the without-rituximab group (10.4% vs. 33.3%, p = 0.014 and 12.2% vs. 39.3% p = 0.0026, respectively). Furthermore, without the application of rituximab was identified as a risk factor for post-HSCT EBV infection via both univariate [hazard ratio (HR) = 4.17, 95%CI (1.52-11.43), p = 0.005] and multivariate analyses [HR = 4.65, 95%CI (1.66-13.0), p = 0.003]. Although the overall survival (OS) probability of the rituximab group was comparable to the without-rituximab group, a markedly improved OS of the rituximab group was found in the malignant disease subgroup (78.9% vs. 42.1%, p = 0.032). The outcomes of graft-versus-host disease, neutrophil and platelet engraftment, other viral infections, and the reconstitution of lymphocytes showed no significant differences between the two groups. CONCLUSIONS: The administration of rituximab before HSCT may prevent EBV infection following HSCT.

Therapeutic drug monitoring and CYP2C19 genotyping guide the application of voriconazole in children.

Background: This study used therapeutic drug monitoring (TDM) and CYP2C19 gene polymorphism analysis to explore the efficacy and safety of different doses of voriconazole (VCZ) for the clinical treatment of pediatric patients, with the aim of providing guidelines for individualized antifungal therapy in children. Methods: Our study enrolled 94 children with 253 VCZ concentrations. The genotyping of CYP2C19 was performed by polymerase chain reaction (PCR)-pyrosequencing. VCZ trough concentration (Ctrough) was detected by high-performance liquid chromatography-tandem mass spectrometry. SPSS 23.0 was used to analyze the correlations between VCZ concentration, CYP2C19 phenotype, adverse effects (AEs), and drug-drug interactions. Results: A total of 94 children aged between 1 and 18 years (median age 6 years) were enrolled in the study. In total, 42.6% of patients reached the therapeutic range at initial dosing, while the remaining patients reached the therapeutic range after the adjustment of the dose or dosing interval. CYP2C19 gene polymorphism was performed in 59 patients. Among these patients, 24 (40.7%) had the normal metabolizer (NM) phenotype, 26 (44.1%) had the intermediate metabolizer (IM) phenotype, and 9 (15.3%) had the poor metabolizer (PM) phenotype. No cases of the rapid metabolizer (RM) or ultrarapid metabolizer (UM) phenotypes were found. The initial VCZ Ctrough was significantly higher in patients with the PM and IM phenotypes than in those with the NM phenotype. The combination of immunosuppressive drugs (ISDs) did not affect VCZ Ctrough. The incidence of AEs was 25.5%, and liver function damage (46.2%) and gastrointestinal reactions (19.2%) were the most common. Conclusions: Our study showed significant individual differences of VCZ metabolism in children. Combining TDM with CYP2C19 gene polymorphism has important guiding significance for individualized antifungal therapy in pediatric patients.

Features of cytomegalovirus infection and evaluation of cytomegalovirus-specific T cells therapy in children's patients following allogeneic hematopoietic stem cell transplantation: A retrospective single-center study.

Cytomegalovirus (CMV) infection remains a critical cause of mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT), despite improvement by pre-emptive antivirus treatment. CMV-specific cytotoxic T lymphocytes (CMV-CTL) are universally used and proven well-tolerance after allo-HSCT in adult clinical trials. However, it is not comprehensively evaluated in children's patients. Herein, we conducted a retrospective study to determine the risk factors of CMV infection and evaluation of CMV-CTL in children patients who underwent allo-HSCT. As result, a significantly poor 5-year overall survival was found in the CMV infection group (87.3 vs. 94.6%, p=0.01). Haploidentical HSCT (haplo-HSCT) was identified as an independent risk factor for CMV infection through both univariate and multivariate analyses (p<0.001, p=0.027, respectively). Furthermore, the cumulative incidence of CMV infection was statistically higher in the haplo-HSCT group compared to the HLA-matched donor group (44.2% vs. 21.6%, p<0.001). Finally, the overall response rate of CMV-CTL was 89.7% (26/29 patients) in CMV infection after allo-HSCT. We concluded that CMV infection following allo-HSCT correlated with increased mortality in children's patients, and haplo-HSCT was an independent risk factor for CMV infection. Adoptive CMV-CTL cell therapy was safe and effective in pediatric patients with CMV infection.

Investigation of the electrocatalytic mechanisms of urea oxidation reaction on the surface of transition metal oxides.

Urea oxidation reaction (UOR) has been widely considered as an alternative anodic reaction to water oxidation for the green production of hydrogen fuel. Due to the high catalytic activity of transition metal oxides towards UOR, various strategies have been developed to improve their syntheses and catalytic properties. However, little is known about the underlying mechanisms of UOR on catalyst surface. In this work, three transition metal oxides, including NiO, Co3O4, and Fe2O3 are investigated as model catalysts. Through analyzing the electrochemical properties by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and operando Raman spectroscopy, it is revealed that NiO has a unique high catalytic activity towards UOR due to simultaneous formation of a thin layer of oxyhydroxide species above 1.40 V vs. RHE in alkaline media. In addition, density functional theory (DFT) calculations further suggest that the adsorption of urea molecules is largely affected by surface interactions resulting in different space configurations, which impose large influences on the consecutive deprotonation and NN formation processes. Overall, results of this work point to the subtle adsorption - kinetics relationship in UOR and highlight the importance of the interfacial electronic interactions on catalyst surface.

Single-Cell Transcriptomic Profiling of Human Retinal Organoids Revealed a Role of IGF1-PHLDA1 Axis in Photoreceptor Precursor Specification.

Purpose: Cone and rod photoreceptors in the retina convert light to electrical signals which are transmitted to the visual cortex of the brain. Abnormal photoreceptor development and degeneration results in blindness. So far, the mechanism that controls photoreceptor specification and its subsequent fate bifurcation remain elusive. Methods: To trace and enrich the human photoreceptor lineage, we first engineered H9 human embryonic stem cell (hESC) reporter line by fusing EGFP to endogenous BLIMP1 using CRISPR/CAS9 gene-editing technology, and then used the cell line to generate 3D retinal organoids. Following EGFP-based cell sorting, single-cell RNA-sequencing was conducted via 10x Genomics Chromium system, and the data were analyzed using Seurat. Immunofluorescence combined with lentivirus-mediated knockdown and overexpression experiments were used as validation approaches. Results: Single-cell transcriptomic profiling revealed that retinal progenitor cells were temporally programmed to differentiate to cone and rod sequentially. We identified PHLDA1 as a novel regulator of photoreceptor specification. PHLDA1 mediated the effects of IGF1 through IGF1R, and inhibited AKT phosphorylation during photoreceptor development. Conclusions: Our data established a transcriptomic cell atlas of the human photoreceptor lineage, and identified IGF1-PHLDA1 axis to regulate human photoreceptor development.

[Effect of ischemia on the structure of bladder in rabbits with partial bladder outlet obstruction].

OBJECTIVE: To compare the structures and functions of rabbit bladder after partial bladder outlet obstruction versus without ischemia so as to explore the effects of ischemia on bladder pathogenesis in rabbits with partial bladder outlet obstruction. METHODS: A total of 64 mature male rabbits were divided into 4 groups (n = 16 each). Four of each group underwent operation to establish an ischemic animal model (ischemia group), another 4 underwent operation to establish a partial bladder outlet obstruction animal model (obstruct group), the other 4 underwent operation to establish an ischemic and partial bladder outlet obstruction animal model (combination group) and the remaining 4 underwent a sham operation as control. The rabbits in 4 groups were evaluated at Week 1, 2, 4 and 8 post-operation respectively. The weight of bladder, the thickness of mucosal, submucosa, muscular layer and placenta percreta and the activities of sarco/endoplasmic reticulum Ca(2+) ATPase citrate synthase of cystic smooth muscle were detected respectively. MASSON staining was used to observe the smooth muscle and collagen in stroma of bladder and S-100 staining for observing the neurons in bladder. RESULTS: In obstruct and combination groups, the weights of bladder at week 1 were (5.10 ± 0.29) g and (4.80 ± 0.37) g respectively. They were both significantly higher than control group [(1.93 ± 0.17) g, all P < 0.05]. The weights of bladder in obstruct and combination groups peaked at Week 4 and they were (18.48 ± 2.03) g and (12.35 ± 0.39) g respectively. The weight of bladder in obstruct group was significantly heavier than combination group in the same terms. And they were both significantly heavier than control and ischemia groups (all P < 0.05). Muscular tissue vicariously thickened during the first 4 weeks, and collagen and stroma increased at Week 4 in obstruct group. Muscular tissue, collagen and stroma all increased initially. But at Week 2 only collagen and stroma increased in combination group. Compare with control group, the other groups all have deletion of neurons, especially in combination group. The activities of sarco/endoplasmic reticulum Ca(2+) ATPase and citrate synthase of cystic smooth muscle of obstruct group peaked at Week 4. In combination group, the activities of sarco/endoplasmic reticulum Ca(2+) ATPase and citrate synthase of cystic smooth muscle were decreased over 2 - 8 weeks. In the same terms, the activities of sarco/endoplasmic reticulum Ca(2+) ATPase and citrate synthase of cystic smooth muscle in control group were significantly higher than those in obstruct and combination groups (all P < 0.05). CONCLUSION: Ischemia can reduce the tolerance of bladder and aggravate the impairment of bladder to partial outlet obstruction.

Study protocol: A cross-sectional study on instrumental support for transitional care among older adults with chronic diseases.

AIMS: In this paper, we present a study aiming to develop a questionnaire on instrumental support for transitional care as a tool for investigating services, staff, equipment and supplies, and funds of transitional care and conduct a cross-sectional study on the current instrumental support for transitional care in older adults with chronic diseases. DESIGN: A cross-sectional study combining instrumental support with transitional care through a mixed-method approach. METHODS: Data are collected through two sources: distribution of the questionnaire to older adults with chronic diseases and interviews with experts from different specialties such as nursing, clinical medicine, geriatrics, sociology and government. RESULTS: The developed questionnaire and expert interviews will be used to investigate the current instrumental support for transitional care among older adults with chronic diseases in China. These findings can help leaders identify areas for improvement in transitional care and contribute to the long-term positive development of transitional care.

Single-Cell Transcriptome Profiling Reveals the Suppressive Role of Retinal Neurons in Microglia Activation Under Diabetes Mellitus.

Diabetic retinopathy, as one of the common complications of diabetes mellitus, is the leading cause of blindness in the working-age population worldwide. The disease is characterized by damage to retinal vasculature, which is associated with the activation of retina microglial and induces chronic neurodegeneration. Previous studies have identified the effects of activated microglial on the retinal neurons, but the cellular and molecular mechanisms underlying microglial activation is largely unknown. Here, we performed scRNA-seq on the retina of non-human primates with diabetes mellitus, and identified cell-type-specific molecular changes of the six major cell types. By identifying the ligand-receptor expression patterns among different cells, we established the interactome of the whole retina. The data showed that TNF-α signal mediated the activation of microglia through an autocrine manner. And we found TGFß2, which was upregulated in cone dramatically by hyperglycemia, inhibited microglia activation at the early stage of diabetic retinopathy. In summary, our study is the first to profile cell-specific molecular changes and the cell-cell interactome of retina under diabetes mellitus, paving a way to dissect the cellular and molecular mechanisms underlying early-stage diabetic retinopathy.

Cotransplantation of Umbilical Cord Mesenchymal Stem Cells Promotes the Engraftment of Umbilical Cord Blood Stem Cells in Iron Overload NOD/SCID Mice.

Iron overload aggravates the difficulty of umbilical cord blood (UCB) stem cell engraftment and reduces the survival of patients undergoing hematopoietic stem cell (HSC) transplantation. Mesenchymal stem cells (MSCs) have been suggested to have a significant role in HSC engraftment. This study aimed to determine the effect of intra-bone marrow (IBM) and i.v. cotransplantation of UBC mononuclear cells (MNCs) and umbilical cord (UC) MSCs on engraftment and hematopoietic recovery in an iron overload hematopoietic microenvironment. The iron overload model was established by dose-escalation intraperitoneal injection of iron dextran in NOD/SCID mice. Iron deposition in the bone marrow, heart, and liver was examined using hematoxylin and eosin (H&E) staining. Serum levels of ferritin and iron status in the liver were measured. The iron overload NOD/SCID mice were sublethally irradiated and divided into 5 groups for transplantation: (1) control group; (2) IBM+ group: IBM injection of combined UCB-MNCs/UC-MSCs; (3) IV+ group: i.v. injection of combined UCB-MNCs/UC-MSCs; (4) IBM group: IBM injection of only UCB-MNCs; and (5) IV group: i.v. injection of UCB-MNCs. At 6 weeks after transplantation, the human CD45+ cells in the bone marrow were analyzed by flow cytometry. The semiquantitative analysis of vascular endothelial growth factor (VEGF-A), osteopontin (OPN), and stromal cell-derived factor-1a (SDF-1a) were examined by immunohistochemical staining (IHC). Compared with the IBM and IV groups, the survival rate and the percentages of human CD45+ cells and CD34+ cells and colony-forming units (CFU) in bone marrow were elevated in the IBM+ and IV+ groups. In addition, the levels of VEGF-A, OPN, and SDF-1a in bone marrow were all higher in the IBM+ and IV+ groups. Our data show that IBM and i.v. cotransplantation of UC-MSCs can improve the engraftment and proliferation of UCB-MNCs in iron overload NOD/SCID mice. The increased expression of VEGF-A, OPN, and SDF-1a in the bone marrow may be involved in improving the hematopoietic microenvironment and promoting the implantation of human UCB stem cells in the bone marrow with iron overload.