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Ischemic heart disease (IHD) is one of the leading causes of mortality worldwide. Moreover, the effects of air pollution have been associated with several cardiovascular diseases (CVDs). The relationship between sandstorm weather and IHD is unknown. The Hexi Corridor is located in northwestern China and is a typical desert region comprising a large area of desert with a high incidence of sandstorms. This study aimed to explore the association between sandstorm weather and IHD-related mortality in this area. We acquired meteorological data of sandstorm weather from 2006 to 2015 from the Gansu Meteorological Bureau, and data regarding deaths due to IHD in five cities within the Hexi Corridor were collected from the death registration system of the Center for Disease Control of Gansu during the same period. Two other cities with few sandstorm events were selected as control regions. The time series method of the generalized additive model (GAM) was used to assess the association between sandstorm weather and IHD-related mortality in the Hexi Corridor. The results showed that the frequency of sandstorms in the Hexi Corridor was higher than that in the control regions (5.48% vs 1.64%, P

Background The incidence of vascular complications varies among different fillers. The main purpose of this study was to compare the risk of embolism between PMMA (Artecoll) and hyaluronic acid (HA, Restylane) after artery injection. Methods Rabbit ears were injected via the central artery with 0.1 ml PMMA (group A), 0.1 ml HA (group B), 0.2 ml PMMA (group C), or 0.2 mL HA (group D), respectively. The formation of transparent emboli was monitored right after injection. Tissue necrosis and histopathological changes were analyzed on day 7. Results With 0.1 ml injected volume, PMMA was dispersed within a few minutes and only 5% of the injected ears had mild necrosis on day 7, while HA tended to form obvious transparent emboli, an indication of blood vessel clotting, and 60% of injected ears showed necrosis on day 7. With 0.2 ml injected volume, PMMA had a risk of complete blood vessel clotting in between 0.1 ml PMMA group and 0.1 ml HA group, and 30% of injected ears had necrosis; in contrast, 100% of 0.2 ml HA-injected ears showed transparent emboli and necrosis. The necrosis areas were significantly increased in the HA groups compared with PMMA groups at the same injection volumes. HA injection also caused dilation of small blood vessels. Conclusion At the same injection volume, PMMA had less risk of embolism compared with HA. With increased injection volume, there were increased risks of embolism and necrosis for both PMMA and HA. No Level Assigned This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. Electronic supplementary material The online version of this article (10.1007/s00266-019-01320-w) contains supplementary material, which is available to authorized users.

Skin wound healing is an intractable problem that represents an urgent clinical need. To solve this problem, a large number of studies have focused on the use of exosomes (EXOs) derived from adipose‐derived stem cells (ADSCs). This review describes the mechanisms whereby ADSCs‐EXOs regulate wound healing and their clinical application. In the wound, ADSCs‐EXOs modulate immune responses and inflammation. They also promote angiogenesis, accelerate proliferation and re‐epithelization of skin cells, and regulate collagen remodelling which inhibits scar hyperplasia. Compared with ADSCs therapeutics, ADSCs‐EXOs have highly stability and are easily stored. Additionally, they are not rejected by the immune system and have a homing effect and their dosage can be easily controlled. ADSCs‐EXOs can improve fat grafting and promote wound healing in patients with diabetes mellitus. They can also act as a carrier and combined scaffold for treatment, leading to scarless cutaneous repair. Overall, ADSCs‐EXOs have the potential to be used in the clinic to promote wound healing., This review describes the mechanisms whereby exosomes (EXOs) derived from adipose‐derived stem cells (ADSCs) regulate wound healing and their clinical application. In the wound, ADSCs‐EXOs modulate immune responses and inflammation, promote angiogenesis, accelerate proliferation and re‐epithelization of skin cells and regulate collagen remodelling, which inhibits scar hyperplasia. ADSCs‐EXOs have the potential to be used in the clinic, as they can improve fat grafting, promote wound healing of diabetic patients and act as a carrier and combined scaffold for treatment, leading to scarless cutaneous repair.

Dedifferentiated adipose cells (DAs) and adipose‑derived stem cells (ADSCs) are two of the primary types of stem cells derived from adipose tissue, which have been reported to possess similar characteristics, but also exhibit unique phenotypic and functional advantages. However, several reports have described inconsistent results regarding their differences in multilineage differentiation function. Moreover, to the best of our knowledge, there are no studies assessing their myogenic ability, or the differences in the transcriptome between the two cell types derived from lipoaspirates via tumescent liposuction from the same donors. The aim of the present study was to compare the properties and expression profiles of these cell types. Subcutaneous adipose tissue of three female patients (aged 23‑30 years) with a physiological BMI (19.1‑23.9 kg/m2) were obtained during tumescent liposuction of the abdomen or the thigh. The stromal vascular fraction and mature adipocytes were obtained via collagenase digestion, and ADSCs and DAs were cultured successively. To determine the differences between DAs and ADSCs after 6‑7 passages, cell proliferation assays, phenotypic assessment, differentiation assays and high‑throughput RNA sequencing (seq) were used. Similar cell morphologies, proliferation dynamics, surface markers and transcriptome expression profiles were observed between the DAs and ADSCs. Whilst there were notable individual differences in the osteogenic, lipogenic, chondrogenic and myogenic abilities of the DAs and ADSCs, it was difficult to determine their differentiation potential based only on the cell source. Interestingly, the myogenic ability was relatively stronger in cells with relatively weaker lipogenic ability. Only 186 differentially expressed genes between the two groups were identified using RNAseq. Several of these genes were involved in biological functions such as transcription regulation, protein translation regulation, cytokine interactions and energy metabolism regulation. The results of the present study suggested a similar functional potential of DAs and ADSCs from young donors undergoing tumescent liposuction operation in regeneration areas and the balance of the differentiative ability of the same cell populations. These data may provide a foundation for further clinical administration of stem cells derived from adipose tissues in therapy.

Objective: As an aberrant response to cutaneous wound healing, keloid scarring is a challenge to cure, and its clinical management remains unsatisfactory. The purpose of this study was to investigate whether mitochondrial function and morphology were impaired in keloid pathology. Approach: Keloid fibroblasts (KFs) and normal skin fibroblasts (NFs) were isolated and cultured from excised samples. A real-time extracellular flux analyzer was used to monitor the oxygen consumption rate for evaluating the mitochondrial respiratory function. Real-time PCR or Western blot was performed to detect the levels of mRNAs or proteins, respectively, including those associated with the tricarboxylic acid cycle, mitochondrial fission and fusion, and mitochondrial biogenesis. The reactive oxygen species (ROS) level and the mitochondrial mass were measured by flow cytometry. Mitochondrial ultrastructure was observed by transmission electron microscopy. Results: Compared with NFs, KFs showed reduced basal oxidative respiration (p

Objective: The study aimed to explore the associations of rs4988300 and rs634008 in the low-density lipoprotein receptor–related protein 5 (LRP5) gene with bone mineral density (BMD), bone turnover markers (BTM), and fractures in elderly patients with osteoporosis (OP).Methods: Our study included 328 unrelated OP patients with or without fractures. Genomic DNA was extracted for genotyping. BTM levels were assessed by electrochemiluminescence (ECL). Dual-energy X-ray absorptiometry (DXA) was employed to measure BMD in the lumbar spine (LS) and proximal femur. Basic features between the OP and fracture groups were analyzed using the t-test. The Chi-square test was performed to analyze the differences in allele and genotype frequencies. The associations of single-nucleotide polymorphisms (SNPs) with BMD and BTM in the subgroups were investigated by the analysis of covariance (ANCOVA) adjusted for confounding factors.Results: In both females and males, individuals with fractures exhibited higher BTM levels and lower BMD values than those with OP (P < 0.05). The allele and genotype frequencies of rs4988300 in the subgroups were significantly different (P < 0.05). In both females and males suffering from OP, participants with rs4988300 GG or rs634008 TT presented lower procollagen I N-terminal propeptide (PINP) levels (P < 0.05). Women with OP carrying rs4988300 GG exhibited lower BMD values at FN and TH (P < 0.05). In both females and males with fractures, individuals carrying rs4988300 GG genotype or rs634008 TT genotype exhibited lower PINP levels and BMD values at FN and TH than those with other genotypes (P < 0.05).Conclusions: Rs4988300 and rs634008 polymorphisms in the LRP5 gene are associated with bone phenotypes in the elderly with OP or fractures.

To investigate the effect of 810 nm near-infrared (NIR) laser on the revascularization of ischemic flaps.It has long been proved that photobiomodulation therapy (PBMT) improves the blood supply of flaps. NIR laser improves the treatment of hypodermis-located lesions and of flap survival, but basic research on the use of 810 nm NIR laser for ischemic flap revascularization is still lacking.We prepared two symmetrical long random-pattern flaps on the backs of 60 rats. Each flap was 6 cm long, 1 cm wide, and 1 cm to the middle line. The flaps were divided into an irradiated flap group and an internal control group. The irradiated flaps underwent postoperative 810 nm laser therapy with the energy density of 11.30 J/cmThe irradiated flaps showed significantly better flap survival than the control flaps. HE staining showed that the irradiated flaps had clear tissue structure and little inflammatory cell infiltration. The control flaps demonstrated comparatively worse results. Vascular endothelial growth factor staining showed that the difference in integrated OD between the irradiated flaps and the control flaps was not statistically significant. α-smooth muscle actin and factor VIII staining showed significantly greater numbers of arterioles and capillaries in the irradiated flaps than the control flaps after 4 days of irradiation.PBMT with 810 nm NIR laser could enhance ischemic flap revascularization and increase flap viability.

Background: Fat grafting technologies are popularly used in plastic and reconstructive surgery. Due to its size limitation, it is hard to directly inject untreated fat tissue into the dermal layer. Nanofat, which was introduced by Tonnard, solves this problem by mechanically emulsifying fat tissue. However, the viability of the cells was greatly destroyed. In this study, we reported a new method by "gently" digesting the fat tissue to produce viable adipocytes, progenitors, and stromal stem cells using collagenase I digestion and centrifugation. This was named "Vivo nanofat" . Methods: Human liposuction aspirates were obtained from five healthy female donors with mean age of 28.7 ± 5.6 years. Colony-forming assay, flow cytometry analysis, and adipogenic and osteogenic induction of the adherent cells from the Vivo nanofat were used to characterize the adipose mesenchymal stem cells (MSCs). To investigate in vivo survival, we respectively injected Vivo nanofat and nanofat subcutaneously to the back of 8-week-old male BALB/c nude mice. Samples were harvested 2 days, 2 weeks, and 4 weeks postinjection for measurement, hematoxylin and eosin staining, and immunostaining. Results: Our results showed that the Vivo nanofat contained a large number of colony-forming cells. These cells expressed MSC markers and had multi-differentiative potential. In vivo transplantation showed that the Vivo nanofat had lower resorption ratio than that of nanofat. The size of the transplanted nanofat was obviously smaller than that of Vivo nanofat 4 weeks postinjection (0.50 ± 0.17 cm vs. 0.81 ± 0.07 cm, t= −5783, P = 0.01). Conclusion: Vivo nanofat may serve as a cell fraction injectable through a fine needle; this could be used for cosmetic applications. Key words: Adipose Tissue; Cell Therapy; Mesenchymal Stromal Cells; Rejuvenation

Human skin fibroblast (HSF) cells were irradiated with different energy lasers to detect cell proliferation, apoptosis, and expression of microRNA‐206 and protein, and to further summarise the therapeutic effect of laser on scar cells. Human scar cell line HSF cells were cultured in three groups. The control group was not irradiated by laser, the low‐energy group was irradiated by 10 J/cm(2) laser, and the high‐energy group was irradiated by 20 J/cm(2) laser. After irradiation, HSF cells were cultured for 20 hours. Cell proliferation was detected by MTT assay. Cell cycle and apoptosis were detected by flow cytometry. Transwell migration assay was used to detect cell migratory ability. Reverse transcription polymerase chain reaction (RT‐PCR) was used to detect miR‐206 and mTOR gene levels. The levels of MMP‐9, Bax, Bcl‐2, cyclin D1, and mTOR signalling pathway proteins were detected by Western blotting assays. The results showed that after laser irradiation, the proliferation of cells decreased, and the difference between the control group and the experimental group was significant (P

Background: The mortality rate of coronary heart disease (CHD) in China is different from region to region, and there are sex, age and urban-rural differences. This study described trend and distribution of CHD in Hexi corridor of Gansu province from 2006 to 2015. Method: The death data of CHD were obtained using the Death Reporting System of Gansu CDC for 2006-2015. The trend of the death cases of CHD by year, month and its distribution by sex, age and region were studied, and the changing characteristics of epidemiology was analyzed. Results: Overall, The mortality rate of CHD in Hexi corridor showed a decline trend from 2006 to 2015, a tendency that higher in winter and spring, and lowest in summer. The relative mortality of males was higher than that of females ( P < 0.05), increased with age ( P < 0.05), and that of rural areas was higher than that of urban areas ( P < 0.05). The trend analysis of death rate for ten-year showed a marked decline in females, an increase in 18-39 years old, a small change in 40-59 years old, a decrease in over 60 years old, and a downward tendency of urban areas. Further analysis showed that the mortality rate of males were higher than that of females in 18-39 years old and 40-59 years old group and also in urban areas group ( P < 0.05), while no sex difference in over 60 years old group and rural areas group ( P > 0.05). Conclusion: The mortality of CHD in Hexi corridor of Gansu province in China was lower than the national average from 2006 to 2015, but increased gradually in specified population such as in males, young and middle-age, rural areas groups. The prevention and control measures should be strengthened in these special populations.

In the past few years, exosomes released from adipose-derived stem cells (abbreviated as ADSCs) have shown promises to provide therapeutic benefits in the fields of regenerative medicine. miRNAs, existing in exosomes, are endogenous, small noncoding RNAs that play important roles in a variety of cellular functions and tumor development. Emerging evidences have indicated that miR-21 is one of the important miRNAs associated with tumor angiogenesis. In this study, we identified the role of exosomes from ADSCs overexpressing miR-21 in regulating/promoting vascularization of endothelial cells. Experimental data indicated an elevated miR-21 level in exosomes released by ADSCs overexpressing miR-21. In vitro matrigel angiogenesis assay showed that exosomes secreted by ADSCs overexpressing miR-21 significantly promoted the vascularization of HUVEC cells (an endothelial cell line). Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB) revealed an upregulation of HIF-1α, VEGF, SDF-1, p-Akt, p-ERK1/2 and downregulation of PTEN in response to miR-21 overexpression, indicating that miR-21 enriched exosomes induced angiogenesis through Akt and ERK activation and also HIF-1α and SDF-1 expression. Our work suggests that exosomes from ADSCs that overexpressing miR-21 can potentially promote vascularization and therefore the transplantation of exosomes from their culture may be suitable for clinical effort in regenerative medicine.

Developing methods for regenerating bones and uncovering the molecular mechanism underlying bone formation have great significance to human health. In the last decade, people have been using adipose-derived stem cells (ADSCs), that are capable of multilineage differentiation, to reconstruct defected bones. Uncovering the molecular mechanisms of the osteoblast differentiation of ADSCs will provide more understanding of ADSCs in the application of bone regeneration and perhaps new methods for osteoporosis treatment. Here we studied how parathyroid hormone (PTH1-34) acts on osteoinduced ADSCs to orchestrate bone formation and how Wnt4 signaling is involved in PTH-promoted bone formation from ADSCs. We found that PTH1-34 can phosphorylate SIK2, upregulate RANKL and downregulate SOST, thereby upregulating Wnt4 to promote the osteogenesis process of ADSCs. Though the knockdown of Wnt4 with shRNA interference barely affects the expression of upstream proteins (i.e., RANKL, SOST), it affects the expression of other downstream osteogenic proteins (i.e., Runx2, Osterix, and Osteocalcin), and then inhibit the osteogenesis process of ADSCs. Overall, PTH can affect the osteogenesis process of ADSCs by regulating SIK2 and Wnt4. We anticipate that this work will provide researchers with new insights into the bone regeneration with ADSCs.

Background: Large-scale muscle tissue engineering remains a major challenge. An axial vascular pedicle and perfusion bioreactor are necessary for the development and maintenance of large-scale engineered muscle to ensure circulation within the construct. We aimed to develop a novel experimental model of a large-scale engineered muscle flap from an existing rat groin fat flap. Methods: A fat flap based on the superficial inferior epigastric vascular pedicle was excised from rats and placed into a perfusion bioreactor. The flaps were kept in the bioreactor for up to 7 weeks, and transdifferentiation of adipose to muscle tissue could have taken place. This system enabled myogenic-differentiation medium flow through the bioreactor at constant pH and oxygen concentration. Assessment of viability was performed by an immunofluorescence assay, histological staining, a calcein-based live/dead test, and through determination of RNA quantity and quality after 1, 3, 5, and 7 weeks. Results: Immunofluorescence staining showed that smooth muscle around vessels was still intact without signs of necrosis or atrophy. The visual assessment of viability by the calcein-based live/dead test revealed viability of the rat adipose tissue preserved in the bioreactor system with permanent perfusion. RNA samples from different experimental conditions were quantified by spectrophotometry, and intact bands of 18S and 28S rRNA were detected by gel electrophoresis, indicating that degradation of RNA was minimal. Conclusions: Flow perfusion maintains the long-term viability of a rat groin engineered muscle flap in vitro, and a large-scale vascularized muscle could be engineered in a perfusion bioreactor. Key words: Culture Ex vivo; Flow Perfusion; Perfusion Bioreactor; Tissue Engineering

Periostin, a secreted extracellular matrix protein, is highly expressed in wound healing and in various types of human cancer and is involved in angiogenesis. Keloids, considered dermal benign tumors, are granulomatous lesions characterized by capillary proliferation. However, the underlying regulatory mechanism of angiogenesis in keloids remains to be elucidated. The present study aimed to examine the effect of periostin on angiogenesis in keloids. The expression of periostin was upregulated and the vessel density was higher in human keloids compared with normal tissue, observed following staining with CD31 and CD105. Periostin demonstrated a markedly positive correlation with blood vessel density, which was assessed using CD31 staining (r=0.711; P

To observe the effects of conditioned medium from keloid fibroblasts under hypoxia on angiogenesis, and to investigate the role of hypoxic microenvironment in invasive growth of keloid.Primary keloid fibroblasts and human umbilical endothelial cells (HUVEC) were cultured as conventional method. Keloid fibroblasts were cultured either in a hypoxic incubator (2% O2) for 48 h or in a normoxic incubator (20% O2) as control. Then those cell culture mediums were collected and mixed with endothelial cell medium by the proportion of 1:1 as conditioned medium. The mRNA and secreted protein of pro-angiogenic factors such as vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and periostin of keloid fibroblasts under hypoxia were detected by real time PCR and ELISA. The proliferation, migration and invasion, tube formation of HUVEC cultured with conditioned medium were evaluated by CCK-8 assay, Transwell assay and matrigel tube formation assay, respectively.Hypoxia increased the expression of VEGF, Ang-1 and periostin in both mRNA (increased by 75%, 43% and 118% respectively, P0.05) and secreted protein (increased by 30.2%, 14.2% and 19.5% respectively, P0.05) levels; the proliferations of HUVEC in hypoxic conditioned medium in 1, 2 and 3 d were 0.67 +/- 0.07, 0.84 +/- 0.09 and 1.08 +/- 0.10 respectively, which were higher compared to those in control group (0.52 +/- 0.08, 0.72 +/- 0.10 and 0.91 + 0.14, P0.05); the numbers of migration, invasion and tube formation of HUVEC were (73.2 +/- 8.9), (56.3 +/- 12.5), (9.66 +/- 1.96) cells/HP, which were higher compared to those in control group [(59.0 +/- 8.0), 35.5 +/- 8.5), (6.5 +/- 1.87) cells/HP, P0.05].Hypoxia increases the expression of pro-angiogenic factors of keloid fibroblasts, and its conditioned medium under hypoxia could promote angiogenesis. The results suggest hypoxic microenvironment may play a significant role in the invasive growth of keloid by inducing angiogenesis.

Periostin, a secreted extracellular matrix protein, is involved in the wound healing and pathological process of various human cancers. Keloid scars are fibroproliferative tumor-like lesions and develop under local hypoxia. Using suppression subtractive hybridization, in a previous study, we found that periostin is overexpressed in keloids compared with hypertrophic scars. However, little is known about the regulation and function of periostin in keloids. In this study, we examined the effects of periostin on the bioactivity of keloid fibroblasts (KFs) in order to determine whether periostin is involved in hypoxia-stimulated keloid pathogenesis by measuring the expression levels of periostin in KFs cultured under hypoxic conditions. We also investigated the association between periostin and hypoxia-inducible factor-1α (HIF-1α). The mRNA, intracellular protein and secreted protein level of periostin was examined by RT-PCR (and quantitative PCR), western blot analysis and enzyme-linked immunosorbent assay (ELISA), respectively. We also used shRNA targeting periostin to knockdown its expression in the KFs. We report that hypoxia (2% O(2)) upregulates both HIF-1α and periostin expression in KFs. In addition, hypoxia-upregulated periostin expression was regulated by HIF-1α. The inhibition of periostin by short hairpin RNA decreased the hypoxia-stimulated proliferation, collagen synthesis, migration and invasion of KFs and altered the cell cycle, but did not affect apoptosis; treatment with recombinant human periostin protein reversed these effects. Periostin also activated the αvβ3 integrin-PI3K/Akt pathway in the KFs. These findings suggest that hypoxia initiates hyperplasia of KFs and increases periostin expression under hypoxic conditions; periostin is involved in the pathogenesis of keloids, which indicates that periostin may be a novel therapeutic target for keloids and other fibroproliferative disorders.

Objective The aim of this study was to examine the gene expression signatures of 2 types of excessive scarring, keloid and hypertrophic scar (HS), through the integrated bioinformatics analysis of multiple published gene expression profile datasets. Methods A literature search of microarray data published in focusing on keloid and HS was performed. The microarray data were reanalyzed to identify the common significantly dysregulated (CSD) genes. The experimental and statistical parameters of the studies were systematically evaluated to reveal any influences on the consensus findings among the studies. Overrepresentation analysis of gene ontology (GO) categories and pathways was used to explore the significantly dysregulated genes functionally associated with the pathogenesis of excessive scarring. Results Seven published microarray studies on keloid and 4 studies on HS were identified. A total of 64 CSD genes were identified in keloid; 9 upregulated CSD genes were identified in HS. The 48 consistently dysregulated genes that overlapped in least 1 keloid study and 1 HS study were defined as the CSD genes in excessive scarring. The differences in the variables associated with the study protocols and data management were systematically documented and evaluated. Activated GO categories and pathways related to skeletal development, binding, extracellular matrix-receptor interaction, and adhesion were found to have significance in excessive scarring, implying a common pathological basis for keloid and HS formation. Notably, the GO categories related to cancer and the TGF-beta signaling pathway were significantly enriched in keloids. Conclusions As gene signatures and molecular markers of excessive scarring, the identified CSD genes may be particularly relevant to disease pathogenesis and serve as new therapeutic targets.

To review the application of and the research progress on acellular matrix (ACM) in cartilage tissue engineering.Related literatures both at home and abroad were retrospected and analyzed.Many researchers improved the properties of cartilage ACM scaffold through co-application of solution diosmosis method, freeze-drying method and physical and chemical cross-linking method etc., and the experimental results of applying cartilage ACM scaffold for the construction of tissue engineered cartilage were closely related to the properties of ACM.ACM has a wide application prospect for the construction of tissue engineered cartilage, and further in-depth studies are needed to improve its property.