Analysis of Risk Factors for Multiantibiotic-Resistant Infections Among Surgical Patients at a Children's Hospital.

BACKGROUND: To identify the potential risk factors for multiantibiotic-resistant infections and provide sufficient evidence for multiantibiotic resistance prevention and control. MATERIALS AND METHODS: We conducted a retrospective study of all patients in pediatric orthopedics, pediatric heart surgery, and pediatric general surgery at a level 3, grade A children's hospital from January to December 2016. The clinical laboratory information monitoring system and the medical record system were used to collect patient information regarding age, surgery type, preoperative length of stay, admission season, incision type, preoperative infection, intraoperative blood loss, postoperative use of invasive equipment, duration of catheter drainage, and timepoint of intraoperative prophylactic antibiotics administration. We used logistic univariate and multivariate regression analysis to analyze the potential risk factors for multiantibiotic-resistant infections among pediatric surgical patients. SPSS 21.0 and Excel software packages were used for the statistical analysis. RESULTS: In total, 2,973 patients met the inclusion criteria: 1,247 patients in pediatric orthopedics, 1,089 patients in pediatric heart surgery, and 637 patients in pediatric general surgery. At the end of the study, 113 patients were multiantibiotic-resistant infection cases; the rate of multiantibiotic-resistant infections was 3.80%, and the detection rate was 84.79%. Multivariate analysis indicated that the multiantibiotic-resistant infection cases were influenced by age, department, admission season, incision type, preoperative infection, and duration of catheter drainage. CONCLUSIONS: Age, department, admission season, incision type, preoperative infection, and duration of catheter drainage may provide possible evidence for prevention and control strategies of multiantibiotic-resistant infections.

p16(INK4A) mediates age-related changes in mesenchymal stem cells derived from human dental pulp through the DNA damage and stress response.

Mesenchymal stem cells derived from human dental pulp (DP-MSCs) are characterized by self-renewal and multi-lineage differentiation, which play important roles in regenerative medicine. Autologous transfers, as non-immunogenic, constitute the safest approach in cellular transplantations. However, their use may be limited by age-related changes. In the study, we compared DP-MSCs isolated from human in five age groups: 5-12 y, 12-20 y, 20-35 y, 35-50 y, and >50 y. We tested the effect of age on proliferation, differentiation, senescence-associated ß-galactosidase (SA-ß-gal), cell cycle and programmed cell death. DP-MSCs showed characteristics of senescence as a function of age. Meanwhile, the expression of p16(INK4A) and γ-H2A.X significantly increased with age, whereas heat shock protein 60 (HSP60) was decreased in the senescent DP-MSCs. Reactive oxygen species (ROS) staining showed the number of ROS-stained cells and the DCFH fluorescent level were higher in the aged group. Further we examined the senescence of DP-MSCs after modulating p16(INK4A) signaling. The results indicated the dysfunction of DP-MSCs was reversed by p16(INK4A) siRNA. In summary, our study indicated p16(INK4A) pathway may play a critical role in DP-MSCs age-related changes and the DNA damage response (DDR) and stress response may be the main mediators of DP-MSCs senescence induced by excessive activation of p16(INK4A) signaling.

Human umbilical cord-derived mesenchymal stem cells downregulate inflammatory responses by shifting the Treg/Th17 profile in experimental colitis.

BACKGROUND/AIMS: The aim of this study was to evaluate the effect and mechanisms of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on immune responses in murine colitis. METHODS: Mice with dextran sulfate sodium (DSS)-induced colitis were injected intraperitoneally with hUC-MSCs or human bone marrow-derived MSCs. The cytokine levels from lamina propria mononuclear cells (LPMCs) and colon tissue were measured using ELISA. Treg and Th17 cells were analyzed using flow cytometry. The proliferation of LPMCs was assessed using Cell Counting Kit-8. RESULTS: hUC-MSCs ameliorate DSS-induced colitis via the downregulation of colon inflammatory responses. Furthermore, hUC-MSCs adjusted modulation of Treg/Th17 cells in the spleen and mesenteric lymph nodes. hUC-MSCs also inhibited LPMCs in vitro. CONCLUSION: hUC-MSCs may be an alternative source of stem cells and are worthy of study in long-term clinical trials.

Age-dependent impaired neurogenic differentiation capacity of dental stem cell is associated with Wnt/ß-catenin signaling.

Two kinds of dental stem cells (DSCs), dental pulp stem cells (DPSCs) and stem cells from human-exfoliated deciduous teeth (SHED), have been identified as novel populations of mesenchymal stem cells that can be induced to differentiate into osteoblasts, chondrocytes, adipocytes, and neuron-like cells in vitro. As we know, both of them originate from the neural crest, but have distinct characteristics and functions in vitro and in vivo. The regeneration potential of DSCs declines with advanced age; however, the mechanism of the impaired potential in DSCs has not been fully explored. In this study, we investigated whether declined neurogenic differentiation capacity is associated with an altered expression of Wnt signaling-related proteins in vitro. We compared stem cells isolated from human dental pulp in two age groups: the exfoliated deciduous teeth (5-12 years), and the third permanent teeth (45-50 years). We found that the expression levels of neuron markers, such as ßIII-tubulin, microtubule-associated protein 2(MAP2), tyrosine hydroxylase (TH), and Nestin were lower in the DPSCs group compared with that in the SHED group; however, in supplementation with human recombinant Wnt1 in the medium, the DPSCs were prone to neural differentiation and expressed higher levels of neurogenic markers. In summary, our study demonstrated that Wnt/ß-catenin signaling may play a vital role in the age-dependent neural differentiation of DSCs. Therefore, DSCs may provide an ideal source of stem cells that can further extend their therapeutic application in nerve injury and neurodegenerative diseases.

TNF-α triggers osteogenic differentiation of human dental pulp stem cells via the NF-κB signalling pathway.

Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cells (MSCs) characterised by self-renewal and multi-lineage differentiation, including chondrocytes, adipocytes, neural cells and osteoblasts, which make it an attractive choice for tissue engineering purposes. Tumour necrosis factor α (TNF-α) had the positive effect on the mineralisation of bone marrow MSCs and stromal cells derived from human adipose tissue. However, the effect of TNF-α on DPSCs is unclear. We found that TNF-α activated the NF-κB pathway during the osteogenic differentiation of DPSCs. TNF-α also increased mineralisation and the expression of bone morphogenetic protein 2 (BMP2), alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2) and collagen type I (COL I) during this process. PDTC, an NF-κB inhibitor, blocked the osteogenic differentiation induced by TNF-α. No effect of TNF-α on proliferation of DPSCs or cell cycle was detected. In summary, TNF-α promotes mineralisation and mineralisation-related gene expression through the NF-κB signalling pathway in DPSCs, which may provide a foundation for autologous transplantation of DPSCs.