Use of Sodium-Glucose Co-Transporter 2 Inhibitors in Patients With Type 2 Diabetes and the Incidence of Retinal Vein Occlusion in Taiwan.

Purpose: The purpose of this study was to evaluate the risk of newly diagnosed retinal vein occlusion (RVO) in patients with type 2 diabetes (T2D) using sodium-glucose cotransporter-2 inhibitors (SGLT-2i) compared to dipeptidyl peptidase-4 inhibitors (DPP-4i). Methods: Claims data from the National Health Insurance Research Database of Taiwan were used in this nationwide retrospective cohort study. A target trial emulation framework was applied. Patients with T2D with no prior diagnosis of RVO who had newly commenced treatment with SGLT-2i or DPP-4i between May 1, 2016, and December 31, 2020, were included. Potential systematic differences in baseline characteristics between the paired groups were controlled using stabilized inverse probability of treatment weighting. The outcome of interest was incident RVO. The hazard ratio (HR) for SGLT-2i compared with that of DPP-4i was estimated using a Cox regression model. Results: Data from 123,567 and 578,665 patients receiving SGLT-2i and DPP-4i, respectively, were analyzed. The incidence of RVO was lower in patients newly receiving SGLT-2i (0.59 events per 1000 person-years) compared to those receiving DPP-4i (0.77 events per 1000 person-years) over a mean follow-up of 1.61 years. SGLT-2i users had a significantly lower risk of developing RVO compared with DPP-4i users (HR = 0.76, 95% confidence interval [CI] = 0.59-0.98). In the individual outcome analysis, SGLT-2i use was significantly associated with a lower risk of branch RVO (HR = 0.71, 95% CI = 0.52-0.96), but not central RVO (HR = 0.84, 95% CI = 0.57-1.24). Conclusions: The risk of developing RVO was lower in patients with T2D receiving SGLT-2i compared with that in those receiving DPP-4i.

A Chinese patent medicine's long-term efficacy on non-dialysis patients with CKD stages 3-5: a retrospective cohort study.

Background: Chinese patent medicine is commonly used in China as an important treatment mechanism to thwart the progression of chronic kidney disease (CKD) stages 3-5, among which Niaoduqing granules are a representative Chinese patent medicine; however, its long-term efficacy on CKD prognosis remains unclear. Methods: Patients were grouped according to Niaoduqing granule prescription duration (non-Niaoduqing granule (non-NDQ) group vs Niaoduqing granule (NDQ) group). Serum creatinine (SCr) variation was compared using a generalized linear mixed model (GLMM). Multivariate Cox regression models were constructed, adjusting for confounding factors, to explore the risk of composite outcomes (receiving renal replacement therapy (RRT) or having an estimated glomerular filtration rate (eGFR)<5 mL/min/1.73 m2, ≥50% decline in the eGFR from the baseline, and doubling of SCr) in individuals consuming Niaoduqing granules. Results: A total of 1,271 patients were included, with a median follow-up duration of 29.71 (12.10, 56.07) months. The mean SCr Z-scores for the non-NDQ group and NDQ group were -0.175 and 0.153, respectively, at baseline (p = 0.015). The coefficients of the NDQ group from visit 1 to visit 5 were -0.207 (95% CI: -0.346, -0.068, p = 0.004), -0.214 (95% CI: 0.389, -0.039, p = 0.017), -0.324 (95% CI: 0.538, -0.109, p = 0.003), -0.502 (95% CI: 0.761, -0.243, p = 0.000), and -0.252 (95% CI: 0.569, 0.065, p = 0.119), respectively. The survival probability was significantly higher in the NDQ group (p = 0.0039). Taking Niaoduqing granules was a significant protective factor for thwarting disease progression (model 1: HR 0.654 (95% CI 0.489-0.875, p = 0.004); model 2: HR 0.646 (95% CI 0.476, 0.877, p = 0.005); and model 3: HR 0.602 (95% CI 0.442, 0.820, p = 0.001)). Conclusion: The long-term use of Niaoduqing granules improved SCr variation and lowered the risk of CKD progression by 39.8%.

Schwann cells acquire a repair phenotype after assembling into spheroids and show enhanced in vivo therapeutic potential for promoting peripheral nerve repair.

The prognosis for postinjury peripheral nerve regeneration remains suboptimal. Although transplantation of exogenous Schwann cells (SCs) has been considered a promising treatment to promote nerve repair, this strategy has been hampered in practice by the limited availability of SC sources and an insufficient postengraftment cell retention rate. In this study, to address these challenges, SCs were aggregated into spheroids before being delivered to an injured rat sciatic nerve. We found that the three-dimensional aggregation of SCs induced their acquisition of a repair phenotype, as indicated by enhanced levels of c-Jun expression/activation and decreased expression of myelin sheath protein. Furthermore, our in vitro results demonstrated the superior potential of the SC spheroid-derived secretome in promoting neurite outgrowth of dorsal root ganglion neurons, enhancing the proliferation and migration of endogenous SCs, and recruiting macrophages. Moreover, transplantation of SC spheroids into rats after sciatic nerve transection effectively increased the postinjury nerve structure restoration and motor functional recovery rates, demonstrating the therapeutic potential of SC spheroids. In summary, transplantation of preassembled SC spheroids may hold great potential for enhancing the cell delivery efficiency and the resultant therapeutic outcome, thereby improving SC-based transplantation approaches for promoting peripheral nerve regeneration.

MACE and Hyperthyroidism Treated With Medication, Radioactive Iodine, or Thyroidectomy.

Importance: Excessive thyroid hormones from hyperthyroidism increase cardiovascular risks. Among 3 available treatments for hyperthyroidism, comparisons of long-term outcomes associated with antithyroid drugs (ATDs), radioactive iodine (RAI), and surgery to treat newly diagnosed hyperthyroidism are lacking. Objective: To compare risks of major adverse cardiovascular events (MACE) and all-cause mortality among patients with hyperthyroidism treated with ATDs, RAI, or surgery. Design, Setting, and Participants: This nationwide cohort study used the Taiwan National Health Insurance Research Database. Patients aged 20 years or older with newly diagnosed hyperthyroidism between 2011 and 2020 were enrolled. Treatment groups were determined within 18 months from diagnosis, with follow-up until the development of MACE, death, or the end date of the database, whichever came first. Data were analyzed from October 2022 through December 2023. Exposures: The ATD group received ATDs only. RAI and surgery groups could receive ATDs before treatment. Anyone who underwent thyroid surgery without RAI was classified into the surgery group and vice versa. Main Outcomes and Measures: The primary outcomes included MACE (a composite outcome of acute myocardial infarction, stroke, heart failure, and cardiovascular mortality) and all-cause mortality. Results: Among 114 062 patients with newly diagnosed hyperthyroidism (mean [SD] age, 44.1 [13.6] years; 83 505 female [73.2%]), 107 052 patients (93.9%) received ATDs alone, 1238 patients (1.1%) received RAI, and 5772 patients (5.1%) underwent surgery during a mean (SD) follow-up of 4.4 (2.5) years. Patients undergoing surgery had a significantly lower risk of MACE (hazard ratio [HR] = 0.76; 95% CI, 0.59-0.98; P = .04), all-cause mortality (HR = 0.53; 95% CI, 0.41-0.68; P < .001), heart failure (HR = 0.33; 95% CI, 0.18-0.59; P < .001), and cardiovascular mortality (HR = 0.45; 95% CI, 0.26-0.79; P = .005) compared with patients receiving ATDs. Compared with ATDs, RAI was associated with lower MACE risk (HR = 0.45; 95% CI, 0.22-0.93; P = .03). Risks for acute myocardial infarction and stroke did not significantly differ between treatment groups. Conclusions and Relevance: In this study, surgery was associated with lower long-term risks of MACE and all-cause mortality, while RAI was associated with a lower MACE risk compared with ATDs.

The Transplantation of 3-Dimensional Spheroids of Adipose-Derived Stem Cells Promotes Achilles Tendon Healing in Rabbits by Enhancing the Proliferation of Tenocytes and Suppressing M1 Macrophages.

BACKGROUND: Tendons have limited regenerative potential, so healing of ruptured tendon tissue requires a prolonged period, and the prognosis is suboptimal. Although stem cell transplantation-based approaches show promise for accelerating tendon repair, the resultant therapeutic efficacy remains unsatisfactory. HYPOTHESIS: The transplantation of stem cells preassembled as 3-dimensional spheroids achieves a superior therapeutic outcome compared with the transplantation of single-cell suspensions. STUDY DESIGN: Controlled laboratory study. METHODS: Adipose-derived stem cells (ADSCs) were assembled as spheroids using a methylcellulose hydrogel system. The secretome of ADSC suspensions or spheroids was collected and utilized to treat tenocytes and macrophages to evaluate their therapeutic potential and investigate the mechanisms underlying their effects. RNA sequencing was performed to investigate the global difference in gene expression between ADSC suspensions and spheroids in an in vitro inflammatory microenvironment. For the in vivo experiment, rabbits that underwent Achilles tendon transection, followed by stump suturing, were randomly assigned to 1 of 3 groups: intratendinous injection of saline, rabbit ADSCs as conventional single-cell suspensions, or preassembled ADSC spheroids. The tendons were harvested for biomechanical testing and histological analysis at 4 weeks postoperatively. RESULTS: Our in vitro results demonstrated that the secretome of ADSCs assembled as spheroids exhibited enhanced modulatory activity in (1) tenocyte proliferation (P = .015) and migration (P = .001) by activating extracellular signal-regulated kinase (ERK) signaling and (2) the suppression of the secretion of interleukin-6 (P = .005) and interleukin-1α (P = .042) by M1 macrophages via the COX-2/PGE2/EP4 signaling axis. Gene expression profiling of cells exposed to an inflammatory milieu revealed significantly enriched terms that were associated with the immune response, cytokines, and tissue remodeling in preassembled ADSC spheroids. Ex vivo fluorescence imaging revealed that the engraftment efficiency of ADSCs in the form of spheroids was higher than that of ADSCs in single-cell suspensions (P = .003). Furthermore, the transplantation of ADSC spheroids showed superior therapeutic effects in promoting the healing of sutured stumps, as evidenced by improvements in the tensile strength (P = .019) and fiber alignment (P < .001) of the repaired tendons. CONCLUSION: The assembly of ADSCs as spheroids significantly advanced their potential to harness tenocytes and macrophages. As a proof of concept, this study clearly demonstrates the effectiveness of using ADSC spheroids to promote tendon regeneration. CLINICAL RELEVANCE: The present study lays a foundation for future clinical applications of stem cell spheroid-based therapy for the management of tendon injuries.

Sodium-glucose co-transporter-2 inhibitors and the risk of venous thromboembolism: A nationwide population-based study and meta-analysis.

AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have off-target effects on haemoconcentration and anti-inflammation. The impact of SGLT-2i on the risk of venous thromboembolism (VTE) in patients with diabetes mellitus (DM) remains unclear. This study aimed to evaluate the risk of newly diagnosed VTE in patients with DM using SGLT-2i in comparison to dipeptidyl peptidase-4 inhibitors (DPP-4i) or glucagon-like peptide-1 receptor agonists (GLP-1RA). MATERIALS AND METHODS: In this nationwide retrospective cohort study, we used data from Taiwan's National Health Insurance Research Database. Patients with diabetes aged 20 years or older who received SGLT-2i, DPP-4i, or GLP-1RA between 1 May 2016, and 31 December 2020, were included. The risks of VTE in SGLT-2i users were compared with those of DPP-4i and GLP-1RA users. A Cox regression model with stabilised inverse probability of treatment weighting was used to calculate hazard ratio (HR) for VTE risk. Additionally, a meta-analysis of relevant articles published before 23 May 2023, was conducted. RESULTS: Data from 136,530 SGLT-2i, 598,280 DPP-4i, and 5760 GLP-1RA users were analysed. SGLT-2i use was associated with a lower risk of VTE than DPP-4i (HR, 0.70; 95% CI, 0.59-0.84; p < 0·001), but not with GLP-1RA (HR, 1.39; 95% CI, 0.32-5.94; p = 0.66). Our meta-analysis further supported these findings (SGLT-2i vs. DPP-4i: HR, 0.71; 95% CI, 0.62-0.82; p < 0·001; SGLT-2i vs. GLP-1RA: HR, 0.91; 95% CI, 0.73-1.15; p = 0.43), suggesting the robustness of our retrospective analysis. CONCLUSIONS: In patients with DM, SGLT-2i was associated with a lower risk of VTE compared to DPP-4i, but not GLP-1RA.

Cryo-EM structure and polymorphic maturation of a viral transduction enhancing amyloid fibril.

Amyloid fibrils have emerged as innovative tools to enhance the transduction efficiency of retroviral vectors in gene therapy strategies. In this study, we used cryo-electron microscopy to analyze the structure of a biotechnologically engineered peptide fibril that enhances retroviral infectivity. Our findings show that the peptide undergoes a time-dependent morphological maturation into polymorphic amyloid fibril structures. The fibrils consist of mated cross-ß sheets that interact by the hydrophobic residues of the amphipathic fibril-forming peptide. The now available structural data help to explain the mechanism of retroviral infectivity enhancement, provide insights into the molecular plasticity of amyloid structures and illuminate the thermodynamic basis of their morphological maturation.

The thermal degradation and soil recovery of thermal treatment of field-weathered decabrominated diphenyl ether-contaminated soil.

A farm at Taoyuan in Taiwan was highly contaminated with decabrominated diphenyl ether (BDE-209), a widely used commercial brominated flame retardant and persistent in the environment, more than 10 years. Since crops are able to absorb and accumulate BDE-209 from soils in our previous research, posing a hazardous risk for humans, it is essential to develop a practical method of soil treatment. Thermal treatment was studied among different approaches. In our previous study (Ko et al., 2022), we found that heating to 450 °C for 30 min achieved a complete removal of BDE-209 in soil. However, the high temperature significantly decreased the original soil organic matter (SOM) from 2.47% to 0.27%, altering the soil texture, damaging microbial biomass, and thus affecting the revegetation after the thermal treatment. Sugarcane bagasse, a common agricultural residue, served as an amendment to restore soil fertility. Current results indicate that 2.5% bagasse can improve the SOM in soil by up to 2.73% and restore its bacterial composition, making the plant growth conditions similar to those of the untreated contaminated soil. In light of the high removal efficiency provided by the 450°C-thermal treatment and the high recovery efficiency of sugarcane bagasse, the strategy presented in this study serves to be a promising method for sustainable remediation.

Associations between maternal phthalate exposure and neonatal neurobehaviors: The Taiwan maternal and infant cohort study (TMICS).

Previous studies have shown associations between prenatal phthalate exposure and neurobehavioral changes in children. However, few studies have focused on neonatal neurobehavioral development. This study aimed to examine the associations between prenatal phthalate exposure and neonatal neurobehavioral development in the early days of life after birth. This cohort study included 283 mother-infant pairs who participated in the Taiwan Mother Infant Cohort Study during 2012-2015. Each mother was interviewed, and urine samples were collected during the third trimester of pregnancy (weeks 29-40). Eleven common phthalate metabolites in maternal urine were analyzed. The Chinese version of the Neonatal Neurobehavioral Examination was used to evaluate early infant neurobehavioral development within five days of birth. We performed multiple linear regressions to explore the associations between phthalate exposure and neonatal neurobehavioral development. Sex differences in the association between phthalate metabolites and neonatal neurobehaviors were noted. Among girls, tertiles of phthalate metabolite concentrations were associated with worse behavioral responses and tone and motor patterns in the high-molecular-weight phthalate (HMW) and low-molecular-weight phthalate (LMW) groups. Girls in the highest tertile of di-2-ethylhexyl phthalate (DEHP) and mono-isobutyl phthalate (MiBP) had a negative association with tone and motor patterns. Girls in the highest tertile of mono-n-butyl phthalate (MnBP) and MiBP showed a negative association with behavioral responses. In contrast, tertiles of phthalate metabolite exposure were associated with improved neurobehaviors in mono-methyl phthalate (MMP) among boys. The highest tertile of MMP was positively associated with behavioral responses, primitive reflexes, and tone and motor patterns. Our findings suggest that maternal phthalate exposure affects neonatal neurobehavioral development in a sex-specific manner. Despite the relatively small sample size, our findings add to the existing research linking maternal phthalate exposure to neonatal neurobehavioral development. Additional research is needed to determine the potential long-term effects of prenatal phthalate exposure on children.

A metagenomics study of hexabromocyclododecane degradation with a soil microbial community.

Hexabromocyclododecanes (HBCDs) are globally prevalent and persistent organic pollutants (POPs) listed by the Stockholm Convention in 2013. They have been detected in many environmental media from waterbodies to Plantae and even in the human body. Due to their highly bioaccumulative characterization, they pose an urgent public health issue. Here, we demonstrate that the indigenous microbial community in the agricultural soil in Taiwan could decompose HBCDs with no additional carbon source incentive. The degradation kinetics reached 0.173 day-1 after the first treatment and 0.104 day-1 after second exposure. With additional C-sources, the rate constants decreased to 0.054-0.097 day-1. The hydroxylic debromination metabolites and ring cleavage long-chain alkane metabolites were identified to support the potential metabolic pathways utilized by the soil microbial communities. The metagenome established by Nanopore sequencing showed significant compositional alteration in the soil microbial community after the HBCD treatment. After ranking, comparing relative abundances, and performing network analyses, several novel bacterial taxa were identified to contribute to HBCD biotransformation, including Herbaspirillum, Sphingomonas, Brevundimonas, Azospirillum, Caulobacter, and Microvirga, through halogenated / aromatic compound degradation, glutathione-S-transferase, and hydrolase activity. We present a compelling and applicable approach combining metagenomics research, degradation kinetics, and metabolomics strategies, which allowed us to decipher the natural attenuation and remediation mechanisms of HBCDs.

Application of U-Net with Global Convolution Network Module in Computer-Aided Tongue Diagnosis.

The rapid development of intelligent manufacturing provides strong support for the intelligent medical service ecosystem. Researchers are committed to building Wise Information Technology of 120 (WIT 120) for residents and medical personnel with the concept of simple smart medical care and through core technologies such as Internet of Things, Big Data Analytics, Artificial Intelligence, and microservice framework, to improve patient safety, medical quality, clinical efficiency, and operational benefits. Among them, how to use computers and deep learning technology to assist in the diagnosis of tongue images and realize intelligent tongue diagnosis has become a major trend. Tongue crack is an important feature of tongue states. Not only does change of tongue crack states reflect objectively and accurately changed circumstances of some typical diseases and TCM syndrome but also semantic segmentation of fissured tongue can combine the other features of tongue states to further improve tongue diagnosis systems' identification accuracy. Although computer tongue diagnosis technology has made great progress, there are few studies on the fissured tongue, and most of them focus on the analysis of tongue coating and body. In this paper, we do systematic and in-depth researches and propose an improved U-Net network for image semantic segmentation of fissured tongue. By introducing the Global Convolution Network module into the encoder part of U-Net, it solves the problem that the encoder part is relatively simple and cannot extract relatively abstract high-level semantic features. Finally, the method is verified by experiments. The improved U-Net network has a better segmentation effect and higher segmentation accuracy for fissured tongue image dataset. It can be used to design a computer-aided tongue diagnosis system.

Injection of hybrid 3D spheroids composed of podocytes, mesenchymal stem cells, and vascular endothelial cells into the renal cortex improves kidney function and replenishes glomerular podocytes.

Podocytes are highly differentiated epithelial cells that are crucial for maintaining the glomerular filtration barrier in the kidney. Podocyte injury followed by depletion is the major cause of pathological progression of kidney diseases. Although cell therapy has been considered a promising alternative approach to kidney transplantation for the treatment of kidney injury, the resultant therapeutic efficacy in terms of improved renal function is limited, possibly owing to significant loss of engrafted cells. Herein, hybrid three-dimensional (3D) cell spheroids composed of podocytes, mesenchymal stem cells, and vascular endothelial cells were designed to mimic the glomerular microenvironment and as a cell delivery vehicle to replenish the podocyte population by cell transplantation. After creating a native glomerulus-like condition, the expression of multiple genes encoding growth factors and basement membrane factors that are strongly associated with podocyte maturation and functionality was significantly enhanced. Our in vivo results demonstrated that intrarenal transplantation of podocytes in the form of hybrid 3D cell spheroids improved engraftment efficiency and replenished glomerular podocytes. Moreover, the proteinuria of the experimental mice with hypertensive nephropathy was effectively reduced. These data clearly demonstrated the potential of hybrid 3D cell spheroids for repairing injured kidneys.

Transplantation of 3D MSC/HUVEC spheroids with neuroprotective and proangiogenic potentials ameliorates ischemic stroke brain injury.

Ischemic stroke, and the consequent brain cell death, is a common cause of death and disability worldwide. Current treatments that primarily aim to relieve symptoms are relatively inefficient in achieving brain tissue regeneration and functional recovery, and thus novel therapeutic options are urgently needed. Although cell-based therapies have shown promise for treating the infarcted brain, a recurring challenge is the inadequate retention and engraftment of transplanted cells at the target tissue, thereby limiting the ultimate therapeutic efficacy. Here, we show that transplantation of preassembled three-dimensional (3D) spheroids of mesenchymal stem cells (MSCs) and vascular endothelial cells (ECs) results in significantly improved cell retention and survival compared with conventional mixed-cell suspensions. The transplanted 3D spheroids exhibit notable neuroprotective, proneurogenic, proangiogenic and anti-scarring potential as evidenced by clear extracellular matrix structure formation and paracrine factor expression and secretion; this ultimately results in increased structural and motor function recovery in the brain of an ischemic stroke mouse model. Therefore, transplantation of MSCs and ECs using the 3D cell spheroid configuration not only reduces cell loss during cell harvesting/administration but also enhances the resultant therapeutic benefit, thus providing important proof-of-concept for future clinical translation.

Prenatal diagnosis of harlequin ichthyosis by ultrasonography: a case report.

Autosomal recessive congenital ichthyosis is a genetically and phenotypically heterogeneous group of skin disorders, including harlequin ichthyosis (HI), lamellar ichthyosis, and bullous congenital ichthyosiform erythroderma. HI is the most phenotypically severe autosomal recessive congenital ichthyosis associated with the mutation of the adenosine triphosphate-binding cassette subfamily A member 12 (ABCA12) gene. The clinical manifestations include generalized hyperkeratotic plaques and deep fissures, ectropion, eclabium, and contractures. However, the severe HI may easily be misdiagnosed as epidermolysis bullosa or syndromic ichthyosis. Meanwhile, no consensus exists about the best used in clinical trials or clinical practice when more elaborate scoring systems have been proposed to evaluate skin xerosis, palmoplantar keratoderma, and disease extension an accurate prenatal diagnosis is necessary. Until the ABCA12 gene was identified as the pathogenic gene, prenatal diagnosis of HI had been performed by the invasive techniques of fetal skin biopsy. Now, advances in ultrasound technology and fetal DNA-based analysis have replaced it. The mortality rate is markedly high and prompt; prenatal diagnosis of neonate HI is critical for appropriate perinatal and postnatal management. It is also essential to prepare parents for future pregnancies and reduce the family's physical and mental distress and financial burden. This report presents a rare case of harlequin ichthyosis diagnosed by the ultrasound and discusses the significance of prenatal ultrasound diagnosis and molecular diagnosis in the prenatal diagnosis of HI.

Efficacy of high intensity focused ultrasound treatment for cystic adenomyosis: a report of four cases.

BACKGROUND: Cystic adenomyosis is a particular type of adenomyosis, High intensity focused ultrasound (HIFU), as a non-invasive method, has also been used to treat adenomyosis. The purpose of this study was to investigate the efficacy, safety, and feasibility of HIFU for the treatment of cystic adenomyosis. METHODS: Diagnosis of cystic adenomyosis was obtained through trans-vaginal ultrasound and magnetic resonance imaging (MRI). Ultrasound-guided HIFU ablation was performed under conscious sedation. The patients were evaluated by the comparison of pre-HIFU and post-HIFU imaging, as well as the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire subscales, consisting of Symptom Severity Score (SSS) and Heath Related Quality of Life (HRQL). RESULTS: HIFU was effective in treating cystic adenomyosis. No complications were observed in the four patients who were successfully treated with HIFU. Compared to preoperative symptoms and patient satisfaction, symptoms at the first follow-up observed significant improvements, with no dysmenorrhea and high health-related quality of life. During the outpatient follow-up of one month, three months, and six months postoperation, the four patients were still without dysmenorrhea and were highly satisfied with the HIFU ablation. CONCLUSIONS: HIFU, as a non-invasive treatment, supplies a safe and effective possibility for the treatment of cystic adenomyosis.

Enhancement of Subcutaneously Transplanted ß Cell Survival Using 3D Stem Cell Spheroids with Proangiogenic and Prosurvival Potential.

Islet transplantation has been demonstrated to be a promising therapy for type 1 diabetes mellitus. Although it is a minimally invasive operating procedure and provides easy access for graft monitoring, subcutaneous transplantation of the islet only has limited therapeutic outcomes, owing to the poor capacity of skin tissue to foster revascularization in a short period. Herein, 3D cell spheroids of clinically accessible umbilical cord blood mesenchymal stem cells and human umbilical vein endothelial cells are formed and employed for codelivery with ß cells subcutaneously. The 3D stem cell spheroids, which can secrete multiple proangiogenic and prosurvival growth factors, induce robust angiogenesis and prevent ß cell graft death, as indicated by the results of in vivo bioluminescent tracking and histological analysis. These experimental data highlight the efficacy of the 3D stem cell spheroids that are fabricated using translationally applicable cell types in promoting the survival and function of subcutaneously transplanted ß cells.

3D Spheroids of Umbilical Cord Blood MSC-Derived Schwann Cells Promote Peripheral Nerve Regeneration.

Schwann cells (SCs) are promising candidates for cell therapy due to their ability to promote peripheral nerve regeneration. However, SC-based therapies are hindered by the lack of a clinically renewable source of SCs. In this study, using a well-defined non-genetic approach, umbilical cord blood mesenchymal stem cells (cbMSCs), a clinically applicable cell type, were phenotypically, epigenetically, and functionally converted into SC-like cells (SCLCs) that stimulated effective sprouting of neuritic processes from neuronal cells. To further enhance their therapeutic capability, the cbMSC-derived SCLCs were assembled into three-dimensional (3D) cell spheroids by using a methylcellulose hydrogel system. The cell-cell and cell-extracellular matrix interactions were well-preserved within the formed 3D SCLC spheroids, and marked increases in neurotrophic, proangiogenic and anti-apoptotic factors were detected compared with cells that were harvested using conventional trypsin-based methods, demonstrating the superior advantage of SCLCs assembled into 3D spheroids. Transplantation of 3D SCLC spheroids into crush-injured rat sciatic nerves effectively promoted the recovery of motor function and enhanced nerve structure regeneration. In summary, by simply assembling cells into a 3D-spheroid conformation, the therapeutic potential of SCLCs derived from clinically available cbMSCs for promoting nerve regeneration was enhanced significantly. Thus, these cells hold great potential for translation to clinical applications for treating peripheral nerve injury.

Investigation of transfusion associated hepatitis C virus infection in Taiwan, 2015-2018.

Continuous strengthening of the safety of blood products to reduce the risk of transfusion-transmitted HCV in recipients is an important issue of Taiwanese government concern. Since 2013, highly sensitivity serology and NAT assays were simultaneously used for blood donation screening to shorten the window period of HIV, HBV and HCV infections. 15 cases of suspected transfusion-transmitted HCV infection were analyzed in 2015-2018. No HCV nucleic acid was detected among a total 91 bags of donated blood. Eleven cases among the 15 suspected recipients were positive for HCV nucleic acid, and 9 recipients had genotype results. Of these 9 recipients, five for genotype 1b (5/9, 55.6%), three for genotype 2a (3/9, 33.3%) and one for genotype 2b (1/9, 11.1%). We will continuously monitor the blood safety of recipients. There have been no confirmed cases of acute hepatitis C (AHC) infection due to transfusions of HCV contaminated blood product in 2015-2018 in Taiwan.