Long-term outcome of retroperitoneoscopic one-trocar-assisted pyeloplasty: a single-center and single-surgeon experience.

PURPOSE: The aim of this study was to assess the long-term outcomes of retroperitoneoscopic one-trocar-assisted pyeloplasty (OTAP) for ureteropelvic junction obstruction (UPJO) in children. METHODS: This retrospective analysis included 70 pediatric cases, all under the age of 5, diagnosed with UPJO and treated with the OTAP technique between May 2011 and June 2013 by a single surgeon. A single 10 mm operative scope with a 5 mm working channel was utilized to mobilize the ureteropelvic junction (UPJ) and exteriorize it through the trocar insertion site. Subsequently, conventional Anderson-Hynes dismembered pyeloplasty was conducted extracorporeally. Patient's demographics, operative time, hospital stay, complications, and success rate were evaluated. RESULTS: Seventy pediatric patients (65 males and 5 females) underwent OTAP, with ages at the time of operation ranging from 1 month to 5 years (mean = 22.6 ± 18.6 months). The mean operative time was 74.8 ± 15.2 min. There was a significant reduction in the mean renal pelvis size from 34.3 ± 8.1 mm preoperatively to 13.8 ± 4.7 mm postoperatively (p < 0.05). Moreover, the mean differential renal function (DRF) increased from 47.9 ± 9.8% preoperatively to 51.2 ± 5.9% postoperatively (p < 0.05). All patients experienced an uneventful postoperative recovery, with a median hospital stay of 3.4 days. The success rate was 95.7%, with a median follow-up time of 75 months (range: 6-125 months). CONCLUSION: OTAP is a safe and feasible minimally invasive technique to correct ureteropelvic junction obstruction in children. It could be considered as a treatment of choice for children under the age of 5 as it combines the advantages of open and retroperitoneoscopic pyeloplasty and presents excellent long-term outcomes. TRIAL REGISTRATION NUMBER: NCT06349161 April 4th, 2024, retrospectively registered.

De novo copy number variations in candidate genomic regions in patients of severe autism spectrum disorder in Vietnam.

Autism spectrum disorder (ASD) is a developmental disorder with a prevalence of around 1% children worldwide and characterized by patient behaviour (communication, social interaction, and personal development). Data on the efficacy of diagnostic tests using copy number variations (CNVs) in candidate genes in ASD is currently around 10% but it is overrepresented by patients of Caucasian background. We report here that the diagnostic success of de novo candidate CNVs in Vietnamese ASD patients is around 6%. We recruited one hundred trios (both parents and a child) where the child was clinically diagnosed with ASD while the parents were not affected. We performed genetic screening to exclude RETT syndrome and Fragile X syndrome and performed genome-wide DNA microarray (aCGH) on all probands and their parents to analyse for de novo CNVs. We detected 1708 non-redundant CNVs in 100 patients and 118 (7%) of them were de novo. Using the filter for known CNVs from the Simons Foundation Autism Research Initiative (SFARI) database, we identified six CNVs (one gain and five loss CNVs) in six patients (3 males and 3 females). Notably, 3 of our patients had a deletion involving the SHANK3 gene-which is the highest compared to previous reports. This is the first report of candidate CNVs in ASD patients from Vietnam and provides the framework for building a CNV based test as the first tier screening for clinical management.

Berberine-loaded polylactic acid nanofiber scaffold as a drug delivery system: The relationship between chemical characteristics, drug-release behavior, and antibacterial efficiency.

Hydrophobic berberine powder (BBR) and hydrophilic BBR nanoparticles (BBR NPs) were loaded into an electrospun polylactic acid (PLA) nanofiber scaffold for modulating the release behavior of BBR in an aqueous medium. The BBR release from the BBR/PLA and BBR NPs/PLA nanofiber scaffolds was investigated in relation to their chemical characteristics, BBR dispersion into nanofibers, and wettability. The BBR release profiles strongly influenced the antibacterial efficiency of the scaffolds over time. When the BBR was loaded, the BBR/PLA nanofiber scaffold exhibited an extremely hydrophobic feature, causing a triphasic release profile in which only 9.8 wt % of the loaded BBR was released in the first 24 h. This resulted in a negligible inhibitory effect against methicillin-resistant Staphylococcus aureus bacteria. Meanwhile, the BBR NPs/PLA nanofiber scaffold had more wettability and higher concentration of BBR NPs dispersed on the surface of PLA nanofibers. This led to a sustained release of 75 wt % of the loaded BBR during the first 24 h, and consequently boosted the antibacterial effectiveness. Moreover, the cytotoxicity test revealed that the BBR NPs/PLA nanofiber scaffold did not induce any changes in morphology and proliferation of MA-104 cell monolayers. It suggests that the BBR/PLA and BBR NPs/PLA nanofiber scaffolds can be used in different biomedical applications, such as wound dressing, drug delivery systems, and tissue engineering, according to the requirement of BBR concentration for the desired therapeutic effects.

Inflammatory mediators drive neuroinflammation in autism spectrum disorder and cerebral palsy.

Inflammation conditions are associated with autism spectrum disorder (ASD) and cerebral palsy (CP), primarily observed in the peripheral immune system. However, the extent of neuro-inflammation and neuro-immune dysregulation remains poorly studied. In this study, we analyzed the composition of cerebrospinal fluid (CSF) to uncover the inflammatory mediators driving the neuro-immune system in ASD and CP patients. Our findings revealed that ASD patients had elevated levels of four inflammatory cytokines (TNF-α, IL-4, IL-21, and BAFF) compared to controls, while CP patients exhibited increased levels of eight inflammatory cytokines (IFN-γ, GM-CSF, TNF-α, IL-2, IL-4, IL-6, IL-17A and IL-12), one anti-inflammatory cytokine (IL-10), and five growth factors (GFs) (NGF-ß, EGF, GDF-15, G-CSF and BMP-9) compared to both controls and ASD patients. Additionally, intrathecal infusion of autologous bone marrow mononuclear cells (BMMNCs) led to a slight decrease in TGF-ß and GDF-15 levels in the CSF of ASD and CP patients, respectively. Our study provides new insights into the molecular composition of CSF in ASD and CP patients, with the potential to develop more effective diagnosis methods and improved treatment for these diseases.Clinical trial registration CSF samples used in this study are from clinical trials NCT03225651, NCT05307536, NCT02569775, NCT03123562, NCT02574923, NCT05472428 and previous reports [7, 9, 17-19].

Outcomes of autologous bone marrow mononuclear cell administration in the treatment of neurologic sequelae in children with spina bifida.

BACKGROUND: To evaluate the safety and efficacy of autologous bone marrow mononuclear cell (BMMNC) infusion in the management of neurological sequelae in children with spina bifida (SB). METHODS: BMMNCs were harvested from bilateral anterior iliac crests. Two intrathecal BMMNC administrations were performed with an interval of 6 months. The measurements of outcomes included clinical assessments, cystomanometry and rectomanometry. RESULTS: Eleven children with SB underwent autologous BMMNC infusions from 2016 to 2020. There were no severe adverse events during the study period. The number of patients requiring assistance to expel stools decreased from 11 before cell infusion to 3 after the second cell infusion. The number of patients who had urine leakage decreased from 9 patients at baseline to 3 patients after the second BMMNC infusion. The mean bladder capacity increased from 127.7 ± 59.2 ml at baseline to 136.3 ± 54.8 ml at six months and to 158.3 ± 56.2 ml at 12 months after BMMNC infusions. Detrusor pressure (pdet) decreased from 32.4 ± 22.0 cm H2O at baseline to 21.9 ± 11.8 cm H2O after 12 months of follow-up. At baseline, six patients could walk independently. After the 2nd infusion, eight patients could walk independently. CONCLUSION: Intrathecal infusions of autologous bone marrow mononuclear cells are safe and may improve bowel, bladder, and motor function in children with SB. TRIAL REGISTRATION: NCT, NCT05472428. Registered July 25, 2022- Retrospectively registered, https://www. CLINICALTRIALS: gov/ct2/show/NCT05472428 .

The Correlation between Peripheral Blood Index and Immune Cell Expansion in Vietnamese Elderly Lung Cancer Patients.

(1) Background: The dysfunction and reduced proliferation of peripheral CD8+ T cells and natural killer (NK) cells have been observed in both aging and cancer patients, thereby challenging the adoption of immune cell therapy in these subjects. In this study, we evaluated the growth of these lymphocytes in elderly cancer patients and the correlation of peripheral blood (PB) indices to their expansion. (2) Method: This retrospective study included 15 lung cancer patients who underwent autologous NK cell and CD8+ T cell therapy between January 2016 and December 2019 and 10 healthy individuals. (3) Results: On average, CD8+ T lymphocytes and NK cells were able to be expanded about 500 times from the PB of elderly lung cancer subjects. Particularly, 95% of the expanded NK cells highly expressed the CD56 marker. The expansion of CD8+ T cells was inversely associated with the CD4+:CD8+ ratio and the frequency of PB-CD4+ T cells in PB. Likewise, the expansion of NK cells was inversely correlated with the frequency of PB-lymphocytes and the number of PB-CD8+ T cells. The growth of CD8+ T cells and NK cells was also inversely correlated with the percentage and number of PB-NK cells. (4) Conclusion: PB indices are intrinsically tied to immune cell health and could be leveraged to determine CD8 T and NK cell proliferation capacity for immune therapies in lung cancer patients.

Cytokine-primed umbilical cord mesenchymal stem cells enhanced therapeutic effects of extracellular vesicles on osteoarthritic chondrocytes.

In recent years, extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) have emerged as a potential cell-free therapy against osteoarthritis (OA). Thus, we investigated the therapeutic effects of EVs released by cytokine-primed umbilical cord-derived MSCs (UCMSCs) on osteoarthritic chondrocyte physiology. Priming UCMSCs individually with transforming growth factor beta (TGFß), interferon alpha (IFNα), or tumor necrosis factor alpha (TNFα) significantly reduced the sorting of miR-181b-3p but not miR-320a-3p; two negative regulators of chondrocyte regeneration, into EVs. However, the EV treatment did not show any significant effect on chondrocyte proliferation. Meanwhile, EVs from both non-priming and cytokine-primed UCMSCs induced migration at later time points of measurement. Moreover, TGFß-primed UCMSCs secreted EVs that could upregulate the expression of chondrogenesis markers (COL2 and ACAN) and downregulate fibrotic markers (COL1 and RUNX2) in chondrocytes. Hence, priming UCMSCs with cytokines can deliver selective therapeutic effects of EV treatment in OA and chondrocyte-related disorders.

Evaluating the Safety and Quality of Life of Colorectal Cancer Patients Treated by Autologous Immune Enhancement Therapy (AIET) in Vinmec International Hospitals.

(1) Colorectal cancer (CRC) is an increasingly prevalent disease with a high mortality rate in recent years. Immune cell-based therapies have received massive attention among scientists, as they have been proven effective as low-toxicity treatments. This study evaluated the safety and effectiveness of autologous immune enhancement therapy (AIET) for CRC. (2) An open-label, single-group study, including twelve patients diagnosed with stages III and IV CRC, was conducted from January 2016 to December 2021. Twelve CRC patients received one to seven infusions of natural killer (NK)-cell and cytotoxic T-lymphocyte (CTL). Multivariate modelling was used to identify factors associated with health-related quality-of-life (HRQoL) scores. (3) After 20−21 days of culture, the NK cells increased 3535-fold, accounting for 85% of the cultured cell population. Likewise, CTLs accounted for 62.4% of the cultured cell population, which was a 1220-fold increase. Furthermore, the QoL improved with increased EORTC QLQ-C30 scores, decreased symptom severity, and reduced impairment in daily living caused by these symptoms (MDASI-GI report). Finally, a 14.3 ± 14.1-month increase in mean survival time was observed at study completion. (4) AIET demonstrated safety and improved survival time and HRQoL for CRC patients in Vietnam.

Stem cell-based therapy for human diseases.

Recent advancements in stem cell technology open a new door for patients suffering from diseases and disorders that have yet to be treated. Stem cell-based therapy, including human pluripotent stem cells (hPSCs) and multipotent mesenchymal stem cells (MSCs), has recently emerged as a key player in regenerative medicine. hPSCs are defined as self-renewable cell types conferring the ability to differentiate into various cellular phenotypes of the human body, including three germ layers. MSCs are multipotent progenitor cells possessing self-renewal ability (limited in vitro) and differentiation potential into mesenchymal lineages, according to the International Society for Cell and Gene Therapy (ISCT). This review provides an update on recent clinical applications using either hPSCs or MSCs derived from bone marrow (BM), adipose tissue (AT), or the umbilical cord (UC) for the treatment of human diseases, including neurological disorders, pulmonary dysfunctions, metabolic/endocrine-related diseases, reproductive disorders, skin burns, and cardiovascular conditions. Moreover, we discuss our own clinical trial experiences on targeted therapies using MSCs in a clinical setting, and we propose and discuss the MSC tissue origin concept and how MSC origin may contribute to the role of MSCs in downstream applications, with the ultimate objective of facilitating translational research in regenerative medicine into clinical applications. The mechanisms discussed here support the proposed hypothesis that BM-MSCs are potentially good candidates for brain and spinal cord injury treatment, AT-MSCs are potentially good candidates for reproductive disorder treatment and skin regeneration, and UC-MSCs are potentially good candidates for pulmonary disease and acute respiratory distress syndrome treatment.

Dioctyl Phthalate-Modified Graphene Nanoplatelets: An Effective Additive for Enhanced Mechanical Properties of Natural Rubber.

Graphene has been extensively considered an ideal additive to improve the mechanical properties of many composite materials, including rubbers, because of its novel strength, high surface area, and remarkable thermal and electron conductivity. However, the pristine graphene shows low dispersibility in the rubber matrix resulting in only slightly enhanced mechanical properties of the rubber composite. In this work, graphene nanoplatelets (GNPs) were modified with dioctyl phthalate (DOP) to improve the dispersibility of the graphene in the natural rubber (NR). The distribution of the DOP-modified GNPs in the NR matrix was investigated using scanning electron microscopy, X-ray diffraction, and Raman spectroscopy. The effect of the modified GNPs' contents on the mechanical properties of the GNPs/NR composite was studied in detail. The results showed that the abrasion resistance of the graphene-reinforced rubber composite significantly improved by 10 times compared to that of the rubber without graphene (from 0.3 to 0.03 g/cycle without and with addition of the 0.3 phr modified GNPs). The addition of the modified GNPs also improved the shear and tensile strength of the rubber composite. The tensile strength and shear strength of the NR/GNPs composite with a GNPs loading of 0.3 phr were determined to be 23.63 MPa and 42.69 N/mm, respectively. Even the presence of the graphene reduced the other mechanical properties such as Shore hardness, elongation at break, and residual elongation; however, these reductions were negligible, which still makes the modified GNPs significant as an effective additive for the natural rubber in applications requiring high abrasion resistance.

Antibiotic Resistance of Helicobacter pylori in Children with Gastritis and Peptic Ulcers in Mekong Delta, Vietnam.

BACKGROUND: Helicobacter pylori (H. pylori) infection causes gastritis, duodenal and gastric ulcers, and gastric cancer. H. pylori eradication efficacy is low worldwide, and antibiotic resistance is the leading cause of therapy failure; therefore, this study was performed to determine the characteristics of antibiotic resistance of H. pylori in children with gastritis, duodenal and gastric ulcer. METHODS: A cross-sectional study was conducted on 237 pediatric patients diagnosed with gastroduodenal inflammation and ulcer at two hospitals in Vietnam from March 2019 to April 2022. Pediatric patients with positive H. pylori tests continued to do E-tests to measure the minimum inhibitory concentration of the antibiotic so that we could prescribe effective antibiotics based on the sensitivity. RESULTS: In 237 pediatric patients (51.1% males) with a median age of 10.3 years (range 5-16 years), endoscopic images showed that inflammatory lesions and peptic ulcers accounted for 69.2% and 30.8%, respectively. Resistance rates of H. pylori were 80.6% to clarithromycin (CLR), 71.7% to amoxicillin (AMX), 49.4% to metronidazole (MTZ), 45.1% to levofloxacin (LEV), and 11.4% to tetracycline (TET); dual resistance to AMX + CLR was 64.2%, AMX + LEV 35%, AMX + MTZ 33.3%, CLR + MTZ 32.5%, and TET + MTZ 7.2%. The frequency of clarithromycin resistance was significantly increased, particularly in pediatric patients who had received prior H. pylori treatment. The percentage of amoxicillin resistance increased with age; amoxicillin resistance of H. pylori was more prevalent among pediatric patients with peptic ulcers than those with gastroduodenal inflammation and higher in males than females. CONCLUSIONS: The proportions of resistance to CLR, AMX, MTZ, and LEV were extremely high, in contrast to TET, which was lower in pediatric patients. Our study suggests that the standard triple therapy with CLR should be limited as the empiric therapy for pediatric patients, and we should consider using eradication regimens with TET for children over 8 years of age if the medical facility is not qualified to perform antibiotic susceptibility tests of H. pylori in the Mekong Delta.

Optimization of human umbilical cord blood-derived mesenchymal stem cell isolation and culture methods in serum- and xeno-free conditions.

BACKGROUND: Although umbilical cord blood (UCB) is identified as a source of mesenchymal stem cells (MSCs) with various advantages, the success in cell isolation is volatile. Therefore, it is necessary to optimize methods of cord blood-derived MSC (UCB-MSC) isolation and culture. In this study, we evaluated the efficiency of UCB-MSC isolation and expansion using different commercially available serum- and xeno-free media and investigated the capacity of autologous serum and plasma as a supplement to support cell proliferation. Additionally, we defined the presence of multilineage-differentiating stress-enduring (Muse) cells in the UCB-MSC population. Functions of UCB-MSC in in vitro angiogenesis processes and anti-cancer were also verified. METHODS: Mononuclear cells were isolated using density gradient separation and cultured in four commercial media kits, as well as four surface coating solutions. UCB-MSCs were characterized and tested on tube formation assay, and co-cultured with SK-MEL cells in a transwell system. RESULTS: The results showed that only StemMACS™ MSC Expansion Media is more appropriate to isolate and culture UCB-MSCs. The cells exhibited a high cell proliferation rate, CFU forming capability, MSC surface marker expression, trilineage differentiate potential, and chromosome stability. In addition, the culture conditions with autologous serum coating and autologous plasma supplement enhanced cell growth and colony forming. This cell population contained Muse cells at rate of 0.3%. Moreover, UCB-MSCs could induce the tube formation of human umbilical vein endothelial cells and inhibit more than 50% of SK-MEL cell growth. CONCLUSIONS: UCB-MSCs could be high-yield isolated and expanded under serum- and xeno-free conditions by using the StemMACS™ MSC Expansion Media kit. Autologous serum coating and plasma supplement enhanced cell proliferation. These UCB-MSCs had effected the tube formation process and an anti-cancer impact.

Differential Development of Umbilical Cord-Derived Mesenchymal Stem Cells During Long-Term Maintenance in Fetal Bovine Serum-Supplemented Medium and Xeno- and Serum-Free Culture Medium.

Umbilical cord-derived mesenchymal stem/stromal cells (UC-MSCs) are believed to have potential for the treatment of various diseases; thus, many scientists have investigated the molecular mechanisms underlying the function of UC-MSCs and, for example, the appropriate media for large-scale UC-MSC expansion to prepare cells for real-world application. In this study, we investigated the cellular morphology, proliferation capacity, surface markers, cellular senescence signals, clonogenic potential, trilineage differentiation capacity, and secreted factors of human primary UC-MSCs in long-term culture from passage 2 (P2) to passage 10 (P10) with either conventional fetal bovine serum (FBS)-supplemented medium or commercial xeno- and serum-free medium (StemMACS™). We found that the cells cultured in both media had similar morphology and marker expression. However, the proliferation kinetics as measured by the cell population doubling time differed in a passage (P2-P10)-dependent manner between the cells cultured in the two media; sustainable growth was observed in cells maintained in xeno- and serum-free medium. Moreover, significant differences in cellular senescence signals were observed, with more aging cells in the cell population cultured in FBS-containing medium. Colony numbers and the day that the first colony appeared were similar; however, UC-MSC colony sizes were smaller when cultured in FBS-containing medium. In addition, the multidifferentiation potential of UC-MSCs cultured in xeno- and serum-free StemMACS medium was maintained during long-term culture, but this potential was lost for adipogenic differentiation at P9. Moreover, secreted epidermal growth factor and vascular endothelial growth factor (VEGF)-A were detected in the conditioned media from UC-MSCs, whereas platelet-derived growth factor was not. Similar expression of these factors was observed in conditioned media of UC-MSCs cultured in StemMACS, but the VEGF level was higher in young UC-MSCs (P6) than in aged UC-MSCs cultured in FBS-supplemented Dulbecco's modified Eagle's medium/F12. Thus, StemMACS is better for UC-MSC expansion than conventional FBS-supplemented culture medium, especially when culturing UC-MSCs for real-world applications.

Novel findings from family-based exome sequencing for children with biliary atresia.

Biliary atresia (BA) is a progressive inflammation and fibrosis of the biliary tree characterized by the obstruction of bile flow, which results in liver failure, scarring and cirrhosis. This study aimed to explore the elusive aetiology of BA by conducting whole exome sequencing for 41 children with BA and their parents (35 trios, including 1 family with 2 BA-diagnosed children and 5 child-mother cases). We exclusively identified and validated a total of 28 variants (17 X-linked, 6 de novo and 5 homozygous) in 25 candidate genes from our BA cohort. These variants were among the 10% most deleterious and had a low minor allele frequency against the employed databases: Kinh Vietnamese (KHV), GnomAD and 1000 Genome Project. Interestingly, AMER1, INVS and OCRL variants were found in unrelated probands and were first reported in a BA cohort. Liver specimens and blood samples showed identical variants, suggesting that somatic variants were unlikely to occur during morphogenesis. Consistent with earlier attempts, this study implicated genetic heterogeneity and non-Mendelian inheritance of BA.

Dynamic entrepreneurship, planned innovation, and firm profitability: evidence from a Southeast Asian country.

This study applies the theory of planned behaviors to evaluate economic outcomes resulting from planned innovation and dynamic entrepreneurship of Vietnamese firms. The analysis uses data on Vietnamese small and medium manufacturing firms from surveys conducted by United Nations University World Institute for Development Economics Research (UNU-WIDER) during 2005-2015. Employing various estimation techniques including normal standard one-side regressions (fixed effect models, panel robust model, and Pds-lasso) and two-side structural two-stage models (extended regression model, treatment effect model, and IV-Lasso), we analyze the impacts of innovation activities on firm profitability in connection to the role of dynamic entrepreneurship and planned innovation. We measure planned innovation by the interaction between intention to innovate and firm innovation activities. The study shows that planned innovation is associated with higher profitability for firms. This holds true for all three innovation activities including introduction of a new product, introduction of a new production process and improvements to existing products/processes. In light of the theory of planned behaviors, entrepreneurial intentions embedded in planned innovation can underlie a comprehensive plan and action that drives the innovation process. The findings suggest that for small and medium enterprises (SMEs) to thrive, willingness to pursue innovation by the firm owners is key to success as the intention to innovate will enable firms to gain a planning advantage. This advantage leads to a better resource allocation within the firms, shaping more effective strategies to implement a planned innovation. Overall, the study provides an important implication for the introduction of support schemes that promote innovation for SMEs in Vietnam. Any support schemes, introduced either by the public or private sector to target SMEs, should be engaged with the group of dynamic entrepreneurs who have intentions to innovate to warrant a higher chance of success.

Type 2 diabetes mellitus duration and obesity alter the efficacy of autologously transplanted bone marrow-derived mesenchymal stem/stromal cells.

Human bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) represent promising stem cell therapy for the treatment of type 2 diabetes mellitus (T2DM), but the results of autologous BM-MSC administration in T2DM patients are contradictory. The purpose of this study was to test the hypothesis that autologous BM-MSC administration in T2DM patient is safe and that the efficacy of the treatment is dependant on the quality of the autologous BM-MSC population and administration routes. T2DM patients were enrolled, randomly assigned (1:1) by a computer-based system into the intravenous and dorsal pancreatic arterial groups. The safety was assessed in all the treated patients, and the efficacy was evaluated based on the absolute changes in the hemoglobin A1c, fasting blood glucose, and C-peptide levels throughout the 12-month follow-up. Our data indicated that autologous BM-MSC administration was well tolerated in 30 T2DM patients. Short-term therapeutic effects were observed in patients with T2DM duration of <10 years and a body mass index <23, which is in line with the phenotypic analysis of the autologous BM-MSC population. T2DM duration directly altered the proliferation rate of BM-MSCs, abrogated the glycolysis and mitochondria respiration of BM-MSCs, and induced the accumulation of mitochondria DNA mutation. Our data suggest that autologous administration of BM-MSCs in the treatment of T2DM should be performed in patients with T2DM duration <10 years and no obesity. Prior to further confirming the effects of T2DM on BM-MSC biology, future work with a larger cohort focusing on patients with different T2DM history is needed to understand the mechanism underlying our observation.

Suspension sutures facilitate single-incision laparoscopic-assisted rectal pull-through for Hirschsprung disease.

BACKGROUND: To present a surgical technique of single-incision laparoscopic-assisted endorectal pull-through (SILEP) with suspension sutures using conventional instruments for Hirschsprung disease (HD) and its long-term follow-up outcomes. METHODS: The procedure began with a 1 cm transumbilical skin incision. Three separate punctures were made in the fascia with a 5 mm scope in the middle and 5 mm and 3 mm ports for working instruments on the left and right, respectively. The first suspension suture was placed to secure the sigmoid colon to the abdominal wall. A window was created through the rectal mesentery, and dissection around the rectum was carried out. The second suspension suture was performed to suspend the rectovesical peritoneal fold or the rectovaginal peritoneal fold to the abdominal wall. Dissection around the rectum was continued downward to approximately 1 cm below the peritoneal fold. Then, the operation was completed by a transanal approach. RESULTS: Forty patients underwent SILEP from March 2013 to April 2015. The median age was 2.7 months (ranging from 1 to 17 months). The mean operative time was 96 ± 23 min. No conversion to an open operation was required. The average hospitalization time was 4.5 ± 2 days. There were no intraoperative or perioperative complications. Long-term follow-up results were obtained from 38 patients. A frequency of defecation from every other day to twice a day was noted for 33 patients (86.8%) and more often for 5 patients (13.2%). Two patients had enterocolitis (5.2%). CONCLUSION: Single-incision laparoscopic rectal pull-through with suspension sutures using conventional instruments is feasible and safe for HD with good long-term outcomes.

Allogeneic human umbilical cord-derived mesenchymal stem/stromal cells for chronic obstructive pulmonary disease (COPD): study protocol for a matched case-control, phase I/II trial.

INTRODUCTION: The global prevalence of chronic obstructive pulmonary disease (COPD) is increasing, and it has become a major public health burden worldwide, including in Vietnam. A large body of preclinical and clinical studies supports the safety of mesenchymal stem/stromal cells (MSCs) in the treatment of lung injury, including COPD. The aim of this trial is to investigate the safety and potential therapeutic efficacy of allogeneic administration of umbilical cord-derived MSCs (UC-MSCs) as a supplementary intervention in combination with standard COPD medication treatments in patients with moderate-to-severe COPD based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019 and Vietnam Ministry of Health's guidelines. METHODS AND ANALYSIS: This matched case-control phase I/II trial is conducted at Vinmec Times City International Hospital, Hanoi, Vietnam between June 2020 and December 2021. In this study, 40 patients will be enrolled and assigned into two age-matched, gender-matched and COPD condition-matched groups, including a UC-MSC group and a control group. Both groups will receive standard COPD medication treatment based on the GOLD 2019 guidelines and the Vietnam Ministry of Health protocol. The UC-MSC group will receive two doses of thawed UC-MSC product with an intervention interval of 3 months. The primary outcome measures will include the incidence of prespecified administration-associated adverse events and serious adverse events. The efficacy will be evaluated based on the absolute changes in the number of admissions, arterial blood gas analysis, lung function and lung fibrosis via CT scan and chest X-ray. The clinical evaluation will be conducted at baseline and 3, 6 and 12 months postintervention. ETHICS AND DISSEMINATION: Ethical approval was secured from the Ethical Committee of Vinmec International Hospital (number:166/2019/QD-VMEC) and Vietnam Ministry of Health (number:2002/QD-BYT). The results will be reported to trial collaborators, publication in peer-reviewed academic journals. TRIAL REGISTRATION NUMBER: NCT04433104.

Influences of Xeno-Free Media on Mesenchymal Stem Cell Expansion for Clinical Application.

Mesenchymal stem/stromal cells (MSCs) are multipotent somatic stem/progenitor cells that can be isolated from various tissues and have attracted increasing attention from the scientific community. This is due to MSCs showing great potential for incurable disease treatment, and most applications of MSCs involve tissue degeneration and treatment of immune- and inflammation-mediated diseases. Conventional MSC cultures contain fetal bovine serum (FBS), which is a common supplement for cell development but is also a risk factor for exposure to animal-derived pathogens. To avoid the risks resulting from the xenogeneic origin and animal-derived pathogens of FBS, xeno-free media have been developed and commercialized to satisfy MSC expansion demands for human clinical applications. This review summarized and provided an overview of xeno-free media that are currently used for MSC expansion. Additionally, we discussed the influences of different xeno-free media on MSC biology with particular regard to cell morphology, surface marker expression, proliferation, differentiation and immunomodulation. The xeno-free media can be serum-free and xeno-free media or media supplemented with some human-originating substances, such as human serum, human platelet lysates, human umbilical cord serum/plasma, or human plasma-derived supplements for cell culture medium. These media have capacity to maintain a spindle-shaped morphology, the expression of typical surface markers, and the capacity of multipotent differentiation and immunomodulation of MSCs. Xeno-free media showed potential for safe use for human clinical treatment. However, the influences of these xeno-free media on MSCs are various and any xeno-free medium should be examined prior to being used for MSC cultures.