Heart Sound Abnormality Detection From Multi-Institutional Collaboration: Introducing a Federated Learning Framework.

OBJECTIVE: Early diagnosis of cardiovascular diseases is a crucial task in medical practice. With the application of computer audition in the healthcare field, artificial intelligence (AI) has been applied to clinical non-invasive intelligent auscultation of heart sounds to provide rapid and effective pre-screening. However, AI models generally require large amounts of data which may cause privacy issues. Unfortunately, it is difficult to collect large amounts of healthcare data from a single centre. METHODS: In this study, we propose federated learning (FL) optimisation strategies for the practical application in multi-centre institutional heart sound databases. The horizontal FL is mainly employed to tackle the privacy problem by aligning the feature spaces of FL participating institutions without information leakage. In addition, techniques based on deep learning have poor interpretability due to their "black-box" property, which limits the feasibility of AI in real medical data. To this end, vertical FL is utilised to address the issues of model interpretability and data scarcity. CONCLUSION: Experimental results demonstrate that, the proposed FL framework can achieve good performance for heart sound abnormality detection by taking the personal privacy protection into account. Moreover, using the federated feature space is beneficial to balance the interpretability of the vertical FL and the privacy of the data. SIGNIFICANCE: This work realises the potential of FL from research to clinical practice, and is expected to have extensive application in the federated smart medical system.

Irisin attenuates vascular remodeling in hypertensive mice induced by Ang II by suppressing Ca2+-dependent endoplasmic reticulum stress in VSMCs.

Vascular remodeling plays a vital role in hypertensive diseases and is an important target for hypertension treatment. Irisin, a newly discovered myokine and adipokine, has been found to have beneficial effects on various cardiovascular diseases. However, the pharmacological effect of irisin in antagonizing hypertension-induced vascular remodeling is not well understood. In the present study, we investigated the protection and mechanisms of irisin against hypertension and vascular remodeling induced by angiotensin II (Ang II). Adult male mice of wild-type, FNDC5 (irisin-precursor) knockout, and FNDC5 overexpression were used to develop hypertension by challenging them with Ang II subcutaneously in the back using a microosmotic pump for 4 weeks. Similar to the attenuation of irisin on Ang II-induced VSMCs remodeling, endogenous FNDC5 ablation exacerbated, and exogenous FNDC5 overexpression alleviated Ang II-induced hypertension and vascular remodeling. Aortic RNA sequencing showed that irisin deficiency exacerbated intracellular calcium imbalance and increased vasoconstriction, which was parallel to the deterioration in both ER calcium dysmetabolism and ER stress. FNDC5 overexpression/exogenous irisin supplementation protected VSMCs from Ang II-induced remodeling by improving endoplasmic reticulum (ER) homeostasis. This improvement includes inhibiting Ca2+ release from the ER and promoting the re-absorption of Ca2+ into the ER, thus relieving Ca2+-dependent ER stress. Furthermore, irisin was confirmed to bind to its receptors, αV/ß5 integrins, to further activate the AMPK pathway and inhibit the p38 pathway, leading to vasoprotection in Ang II-insulted VSMCs. These results indicate that irisin protects against hypertension and vascular remodeling in Ang II-challenged mice by restoring calcium homeostasis and attenuating ER stress in VSMCs via activating AMPK and suppressing p38 signaling.

Evidence-based core information for health communication of tobacco control: The effect of smoking on risks of female disease.

Objective: Cigarettes have become the the biggest killer of contemporary female's health and beauty. What kind of health information is suitable for the general public is an important issue to be discussed globally. The purpose of this study is to generate systematic, rigorous, public-demand-oriented and appropriate core information relevant to tobacco control based on the best available evidence, combined with audience preferences and pre-dissemination content review from multidisciplinary expertise in order to improve the effectiveness of health communication of tobacco control. Methods: Relevant systematic reviews meta-analysis that reported smoking on risks of female disease were identified by searching PubMed, Embase, the Cochrane Library, Web of Science, Clinical Trials.gov, and the International Clinical Trial Registry Platform. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) process was applied to assess the evidence in order to make rigorous core information. The audience prevalence survey was conducted to ensure that core information was targeted and tailored. Finally, the expert assessment was used for a pre-dissemination content review and to evaluate whether the core information was appropriate or not. Results: The final core information consisted of eight parts concerning the effects of smoking and female cardiovascular disease, diabetes, rheumatoid arthritis, respiratory disease, digestive system disease, mental disease, non-pregnant female reproductive system disease, as well as pregnant women and their fetuses. A total of 35 items of core information suitable for dissemination was included and the quality of evidence, the degree of public demand and the outcome of pre-dissemination content review were reported. Conclusion: The core information related to female cardiovascular system diseases, as well as liver cancer and upper gastrointestinal cancer is the preferred content for health communication of tobacco control. The quality of evidence for core information related to pregnant women and their infants, as well as diseases of reproductive system, respiratory system, and diabetes needs to be improved to meet high public demand. The core information related to mental disease is more suitable for dissemination to patients with mental illness than to the general public. Besides, dissemination of core information should be individualized. Evidence-based Core Information for Health Communication of Tobacco Control would be helpful to provide evidence support for health communication related to tobacco control and enhance public health literacy for international communities that have high smoking prevalence and related disease burden.

Protective effect of MOTS-c on acute lung injury induced by lipopolysaccharide in mice.

MOTS-c (mitochondrial open-reading-frame of the twelve S rRNA-c), a mitochondrial-derived 16-amino acid peptide, targets the methionine-folate cycle, increases 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) levels, and eventually activates AMP-activated protein kinase (AMPK). AMPK activation can attenuate neutrophil pro-inflammatory activity and attenuates lipoteichoic acid (LTA) and lipopolysaccharide (LPS) induced acute lung injury (ALI) in mice. However, to our knowledge, the role of MOTS-c in LPS-induced ALI remains unclear. Hence, we investigated the potential effectiveness and underlying mechanism of MOTS-c against LPS-induced ALI in mice. The intraperitoneal administration of MOTS-c (5 mg/kg, i.p., bid, 6 days) before intratracheal LPS instillation attenuated body weight loss and pulmonary edema, inhibited neutrophilic tissue infiltration in lung tissue, downregulated the expression of cytokine-induced neutrophil chemoattractant-1 (CINC-1) and intercellular cell adhesion molecule-1 (ICAM-1) in lung tissues, decreased the levels of TNF-α, IL-1ß, and IL-6, and increased the expression of IL-10 and SOD in serum, lung tissue, and bronchoalvelolar lavage fluid (BALF). Moreover, MOTS-c treatment significantly promoted p-AMPKα and SIRT1 expression and suppressed LPS-induced ERK, JNK, p38, p65, and STAT3 activation in the mouse lung tissues. Collectively, these findings suggest that MOTS-c plays important roles in protecting the lungs from the inflammatory effects of LPS-induced ALI. The effects of MOTS-c are probably orchestrated by activating AMPK and SIRT1, inhibiting ERK, JNK, p65, and STAT3 signaling pathways. Thus, MOTS-c appears to be a novel and promising candidate for the treatment of ALI.

[Physiological Function and Structural Basis of Bcl-2 Family Proteins]. / Bcl-2家族蛋白的生理功能及结构基础.

Apoptosis is an important biological process that plays a key role in the regulation of cell fate and homeostasis. The B-cell lymphoma-2 (Bcl-2) family proteins are important regulators of the apoptotic pathway, and their dysfunction is associated with a variety of diseases, including cancer, neurodegenerative and autoimmune diseases. In the past decade, a large number of research work on the physiological functions and atomic structures of Bcl-2 family proteins have been reported, which has deepened our understanding of the molecular mechanism and pathological significance of Bcl-2 family proteins. Recently, new drugs targeting different Bcl-2 proteins have been developed and used in clinics or tested in clinical trials. However, the complexity and diversity in functions and structures of Bcl-2 family have left many unsolved problems. This article summarizes current knowledge of the structure and function of Bcl-2 family proteins and discusses the pharmacological significance of Bcl-2 proteins as effective therapeutic targets.

A Critical Role of the IL-1ß-IL-1R Signaling Pathway in Skin Inflammation and Psoriasis Pathogenesis.

The IL-1 signaling pathway has been shown to play a critical role in the pathogenesis of chronic, autoinflammatory skin diseases such as psoriasis. However, the exact cellular and molecular mechanisms have not been fully understood. Here, we show that IL-1ß is significantly elevated in psoriatic lesional skin and imiquimod-treated mouse skin. In addition, IL-1R signaling appears to correlate with psoriasis disease progression and treatment response. IL-1 signaling in both dermal γδ T cells and other cells such as keratinocytes is essential to an IMQ-induced skin inflammation. IL-1ß induces dermal γδ T cell proliferation and IL-17 production in mice. In addition, IL-1ß stimulates keratinocytes to secrete chemokines that preferentially chemoattract peripheral CD27- CCR6+IL-17 capable of producing γδ T cells (γδT17). Further studies showed that endogenous IL-1ß secretion is regulated by skin commensals to maintain dermal γδT17 homeostasis in mice. Mouse skin associated with Corynebacterium species, bacteria enriched in human psoriatic lesional skin, has increased IL-1ß and dermal γδT17 cell expansion. Thus, the IL-1ß-IL-1R signaling pathway may contribute to skin inflammation and psoriasis pathogenesis via the direct regulation of dermal IL-17-producing cells and stimulation of keratinocytes for amplifying inflammatory cascade.

Management of individuals with chronic hepatitis B virus infection and persistent normal or mildly elevated aminotransferase levels.

No consensus exists with respect to positive hepatitis B virus (HBV) DNA results and persistent normal or mildly elevated alanine aminotransferase (ALT). The aim of this study is to investigate the appropriate management and prognosis of these populations with chronic hepatitis B (CHB). A total of 235 subjects with positive HBV DNA results and persistent normal or mildly elevated ALT were enrolled in this study. Liver biopsy and liver stiffness measurements (LSM) were performed in all participants at baseline. Antiviral therapy was initiated in patients with significant hepatic inflammation (G ≥ 2) and/or fibrosis (S ≥ 2). The patients were divided into entecavir and adefovir groups based on HBV DNA load (>2000 IU/mL vs <2000 IU/mL). The liver biopsies were repeated at 72 weeks for the patients received antiviral therapy. We found that 112 subjects were hepatitis B e antigen (HBeAg) positive, and 123 subjects were negative. The corresponding median ALTs were 46 (39.5-52.5) and 48 (41.5-57.0) U/mL, respectively. G ≥ 2 and/or S ≥ 2 diseases were present in 48.8% (82/168) of the HBeAg-positive and 51.2% (86/168) of HBeAg-negative patients, respectively. In addition, 96 HBeAg-positive and 72 HBeAg-negative patients were divided into entecavir and adefovir groups. Meanwhile, liver biopsies had greater diagnostic accuracy for determining cirrhosis than LSM (0.711 vs 1.0, P < 0.0001). At the end of the study period, undetectable HBV DNA levels and normal ALT levels were observed in CHB-infected patients. Furthermore, the patients showed histologic improvement at 72 weeks compared with baseline measurements (G, 1.72 ± 1.00 vs 0.73 ± 0.88, P = 0.0002; S, 1.484 ± 0.90 vs 0.99 ± 1.13, P < 0.0001). Collectively, liver biopsy enhanced diagnostic accuracy for CHB-infected individuals with persistent normal or mildly elevated aminotransferase levels. Moreover, antiviral therapy can improve or regress the hepatic fibrosis and cirrhosis.

Trends and clinicopathological predictors of axillary evaluation in ductal carcinoma in situ patients treated with breast-conserving therapy.

The aim of this study was to investigate the trends of axillary lymph node evaluation in ductal carcinoma in situ (DCIS) patients treated with breast-conserving therapy (BCT) and to identify the clinicopathological predictors of axillary evaluation. DCIS patients treated with BCT in 2006-2015 at our institute were retrospectively included in the analysis. Patients were categorized into three groups: sentinel lymph node biopsy (SLNB), axillary lymph node dissection (ALND), and non-evaluation. Univariate and multivariate logistic regression analyses were performed to identify factors that predicted axillary evaluation. A total of 315 patients were identified, among whom 135 underwent SLNB, and 15 underwent ALND. The proportion of patients who underwent axillary evaluation increased from 33.0% in 2006-2010 to 53.8% in 2011-2015 (P < 0.001), however, no patients had lymph node metastasis based on final pathology. In multivariate analysis, high-grade tumor favored axillary evaluation (OR = 4.376, 95% CI:1.410-13.586, P = 0.011); while excision biopsy favored no axillary evaluation compared with other biopsy methods (OR = 0.418, 95% CI: 0.192-0.909, P = 0.028). Subgroup analysis of patients treated in 2011-2015 revealed that high-grade tumor (OR = 5.898, 95% CI: 1.626-21.390, P = 0.007) and palpable breast lump (OR = 2.497, 95% CI: 1.037-6.011, P = 0.041) were independent predictors of axillary lymph node evaluation. Despite the significant decrease in ALND and a concerning overuse of SLNB, we identified no axillary lymph node metastasis, which justified omitting axillary evaluation in these patients. High-grade tumor, palpable lump, and biopsy method were independent predictors of axillary evaluations. Excision biopsy of suspicious DCIS lesions may potentially preclude the invasive component of the disease and help to avoid axillary surgery.

Analysis of Mechanical Behavior of Dermal Fibroblasts Obtained From Various Anatomical Sites in Humans.

PURPOSE: Facial skin fibroblasts imposed with cyclic stretch at 10% magnitude display considerable mechanotransduction properties and biochemical reactions in our previous study. However, it is poorly understood how these shared traits are fully parallel to the common features across all fibroblasts derived from different skin-based anatomical regions in response to cyclic stretch stimulation. Thus, the purpose of this study was to evaluate the effects of various cyclic stretches on fibroblasts derived from multiple anatomical skin sites of human bodies, and the optimal stretch magnitude was defined based on the changes to cell mechanical behavior. METHODS: Fibroblasts from skin areas of the scalp, anterior chest, suprapubic, axilla, and planta were cultured and characterized in vitro. Cyclic stretch at 0%, 5%, 10%, 15%, and 20% magnitudes was imposed at a loading frequency of 0.1 Hz for 48 hours, and thereafter, the mechanical behavior and biochemical reaction of the dermal fibroblasts were analyzed. RESULTS: Dermal fibroblasts from various anatomical sites preconditioned with varying cyclic stretch led to an evident increase in the cell proliferation ability, the expression of integrin ß1 and p130 Crk-associated substrate messenger RNA and protein, and the productions of type I collagen and transforming growth factor ß1, most importantly in a strain magnitude-dependent manner with the peak appearing in the range of 10% to 15% magnitude cyclic stretch. CONCLUSIONS: These findings may facilitate the subsequent studies on the conversion of normal skin fibroblasts into hypertrophic scar cells, which should be considered in an interpretation of the mechanisms of hypertrophic scarring and skin mechanics.

A prospective study of breast anthropomorphic measurements, volume and ptosis in 605 Asian patients with breast cancer or benign breast disease.

OBJECTIVES: The current study aims to summarize breast anthropomorphic measurement features in Chinese patients with breast diseases and to investigate their potential correlations with demographic factors. MATERIALS AND METHODS: Fifteen breast anthropomorphic parameters of 605 Chinese female patients were collected prospectively. Breast ptosis status was scaled by two methods and breast volume was calculated according to a modified formula of BREAST-V. RESULTS: Among 1210 breasts, the average breast volume was 340.0±109.1 ml (91.8-919.2 ml). The distance from the nipple to the inframammary fold was 7.5±1.6 cm in the standing position. The width of the breast base was 14.3±1.4 cm (8.5-23.5 cm). The incidence of breast ptosis was 22.8% (274/1204), of which 37 (23.5%) and 79 (31.7%) women had severe ptosis assessed by different criteria. Increased height (OR[odds ratio] = 1.500, P<0.001), post-menopausal status (OR = 1.463, P = 0.02), increased BMI, breastfeeding for 7-12 months (OR = 1.882, P = 0.008) and more than one year (OR = 2.367, P = 0.001) were risk factors for an increased breast volume. Post-menopausal status (OR = 2.390, P<0.001 and OR = 2.621, P<0.001 for different scales), BMI≥24.7 kg/m2 (OR = 3.149, P<0.001 and OR = 2.495, P = 0.002), breastfeeding for 7-12 months (OR = 4.136, P = 0.004 and OR = 4.010, P = 0.002), and breastfeeding for more than one year (OR = 6.934, P<0.001 and OR = 6.707, P<0.001) were independent risk factors for breast ptosis. CONCLUSIONS: The current study provides anthropomorphic measurements data of Chinese women with breast diseases, which are useful for cosmetic and reconstructive breast surgery decisions. Post-menopausal status, increased BMI, and breastfeeding for more than six months were independent risk factors for both increased breast volume and breast ptosis.

Surgical management of breast cancer in China: A 15-year single-center retrospective study of 18,502 patients.

The aim of the study was to review the surgical trends in breast cancer treatment in China over the past 15 years and to explore the possible factors related to the choice of surgical modality.The medical records of 18,502 patients with unilateral early stage breast cancer who underwent surgery from January 1999 to December 2013 at our institute were retrospectively reviewed. The utilization of different surgical modalities and the associated clinicopathological factors were analyzed. Furthermore, the prognostic role of surgical modality was also evaluated.The median patient age was 50.0 years. According to the pTNM staging system, 12.5% of the patients were classified as stage 0; 30.2% as stage I; 40.0% as stage II; and 17.3% as stage III. In total, 9.3% of the patients could not be staged. Overall, 67.1% of the breast cancer cases were estrogen receptor (ER) positive. The pattern of breast cancer surgery has changed tremendously over the past 15 years (P < 0.001). The pattern of mastectomy has shifted from radical mastectomy to modified radical mastectomy and simple mastectomy + sentinel lymph node biopsy. A total of 81.7% of the patients underwent mastectomy without immediate reconstruction, 15.2% underwent breast-conserving surgery (BCS), and 3.7% received immediate breast reconstruction after mastectomy. Age, TNM staging, and pathological characteristics greatly affected the choice of surgical modality. The 5-year recurrence-free survival (RFS) rates for the mastectomy, BCS, and reconstruction groups were 87.6%, 93.2%, and 91.7%, respectively (P < 0.001); the RFS rate was likely affected by distant recurrence instead of loco-regional recurrence. We also identified improved RFS over time, stratified by surgical modality and tumor stage. Multivariate Cox-regression analysis revealed that time of treatment, tumor stage, tumor grade, LVI status, and ER status were independent prognostic factors for RFS in our cohort, whereas surgical modality was not.Mastectomy remains the most prevalent surgical modality used to manage early stage breast cancer in China, although the utilization of BCS has increased in the past decade. However, surgical management was not a prognostic factor for RFS. The selection of appropriate patients depended on the assessment of multiple clinicopathological factors, which is essential for making surgical decisions.

Current status of breast reconstruction in China: an experience of 951 breast reconstructions from a single institute.

BACKGROUND: Since mastectomy remained the primary strategy for treating breast cancer in China, post-mastectomy reconstruction is of great importance in the Chinese population. The current study aimed to assess the current status of breast reconstruction in China. METHODS: We reviewed all patients who received breast reconstruction from August 2000 to July 2015 in the Department of Breast Surgery in our institute. Patients' baseline characteristics, reconstruction strategy, final pathology and loco-regional recurrence (LRR) information were collected. RESULTS: A total of 951 breast reconstructions were conducted during the past 15 years, among which 247 (27.0%) were abdominal flap reconstruction; 471 (51.5%) were latissimus dorsi myocutaneous ± implant; and 233 (25.5%) were prosthesis-based reconstruction. The majority of cases (78.1%) were invasive breast cancer and up to 894 cases (94.0%) were immediate reconstruction. Prosthesis-based reconstruction rapidly increased in recent years, and was associated with bilateral reconstruction, contralateral augmentation and higher complications. 18 patients (2.0%) developed local-regional recurrence at the median follow-up time of 26.6 months (range, 3.7-62.0 months). A total of 66 nipple-areolar complex-sparing mastectomies (NSMs) (6.9%) were performed, none of which developed recurrence. CONCLUSIONS: Breast reconstruction cases increased over the 15 years with the change of paradigm. Most strikingly, prosthesis-based reconstruction rapidly gained its prevalence and became the most common strategy. NSM was only performed for highly selected patients. Patients with breast reconstruction were able to achieve satisfactory loco-regional control in our cohort.

Potential new method of design for reconstruction of complicated mandibular defects: a virtual deformable mandibular model.

The treatment of complicated mandibular defects, including misshaped and missing bones, is challenging, and the success of reconstruction depends to a large extent on the formulation of a precise surgical plan. There is still no ideal preoperative method of design for reconstruction to deal with large, cross-midline, mandibular, segmental defects. We have built a virtual deformable mandibular model (VDMM) with 3-dimensional animation software. Sixteen handles were set on the model, and these could be easily controlled with a computer mouse to change the morphology of the deformable mandibular model. The computed tomographic (CT) data from 10 normal skulls was used to validate the adjustability of the VDMM. According to the positions of the mandibular fossa of the temporomandibular joint, the maxillary dental arch, and the craniomaxillofacial profile, the model could be adjusted to an ideal contour, which was coordinated with the skull. The VDMM was then adjusted further according to the morphology of the original mandible. A 3-dimensional comparison was made between the model of the deformed mandible and the original mandible. Using 16 control handles, the VDMM could be adjusted to a new outline, which was similar in shape to the original mandible. Within 3mm deviation either way, the absolute mean distribution of deviation between the contour of the deformed model and the original mandible was 92.5%. The VDMM might be useful for preoperative design of reconstruction of complicated mandibular defects.

Systemic BMSC homing in the regeneration of pulp-like tissue and the enhancing effect of stromal cell-derived factor-1 on BMSC homing.

Pulp regeneration caused by endogenous cells homing has become the new research spot in endodontics. However, the source of functional cells that are involved in and contributed to the reconstituting process has not been identified. In this study, the possible role of systemical BMSC in pulp regeneration and the effect of stromal cell-derived factor-1 (SDF-1) on stem cell recruitment and angiogenesis were evaluated. 54 mice were divided into three groups: SDF-1 group (subcutaneous pockets containing roots with SDF-1 absorbed neutralized collagen gel and the green fluorescent protein (GFP) positive BMSCs transplantation via the tail vein), SDF-1-free group (pockets containing roots with gel alone and GFP + BMSCs transplantation) and Control group (pockets containing roots with gel alone). The animals were sacrificed after the roots were implanted into subcutaneous pockets for 3 weeks. Histomorphometric analysis was performed to evaluate the regenerated tissue in the canal by hematoxylin and eosin (HE) staining. The homing of the transplanted BMSCs was monitored with a fluorescence microscope and immunohistochemical analysis. The expression of ALP in new formed tissue was detected immunohistochemically. Dental-pulp-like tissue and new vessels were regenerated and GFP-positive BMSCs and expression of ALP could be observed in both SDF-1 group and SDF-1-free group. Furthermore, more GFP+ cells, stronger expression of ALP and stronger angiogenesis were found in the SDF-1 group than in the SDF-1-free group. To conclude, systemic BMSC can home to the root canal and participate in dental-pulp-like tissue regeneration. Intracanal application of SDF-1 may enhance BMSC homing efficiency and angiogenesis.

Surgical management for early-stage bilateral breast cancer patients in China.

BACKGROUND: The aim of this study was to investigate the current surgical management strategy for bilateral breast cancer (BBC) patients and to assess the changes in this strategy in China. METHODS: This is a retrospective review of all patients with early-stage BBC who underwent surgical treatment at the Fudan University Shanghai Cancer Center between June 2007 and June 2014. RESULTS: A total of 15,337 patients with primary breast cancer were identified. Of these patients, 218 (1.5%) suffered from synchronous bilateral breast cancer (sBBC), and 296 (2.0%) suffered from metachronous bilateral breast cancer (mBBC). Patients with a lobular carcinoma component, those with estrogen receptor-positive cancer, and those with an accompanying sclerosing adenosis in the affected breast tended to develop BBC. The rates of bilateral mastectomy, breast conserving therapy, reconstruction, and combined surgeries were 86.2%, 6.4%, 3.7%, and 3.7%, respectively, for patients with sBBC and 81.1%, 4.4%, 3.0%, and 11.5%, respectively, for patients with mBBC. The interval between bilateral cancers, age at first diagnosis of breast cancer, histopathological type, and stage have significant impacts on the choice of surgery for patients with BBC. CONCLUSIONS: Bilateral mastectomy was the dominant surgical management for patients with BBC in China, despite the increased application of breast reconstruction surgery observed in recent years. Bilateral prosthetic breast reconstruction was the ideal choice for patients with sBBC. Chinese surgeons should take responsibility for patient education and inform their patients about their surgical options.

Systemically transplanted human gingiva-derived mesenchymal stem cells contributing to bone tissue regeneration.

As novel postnatal stem cells, gingiva-derived mesenchymal stem cells (GMSCs) have been considered as an ideal candidate cell resource for tissue engineering and cell-based therapies. GMSCs implanted into sites of injury have been confirmed to promote the injury repair. However, no studies have demonstrated whether systemically transplanted GMSCs can home to the bone injuries and contribute to the new bone formation in vivo. In this study, we transplanted human GMSCs into C57BL/6J mice with defects in mandibular bone via the tail vein to explore the capacity of transplanted GMSCs to promote bone regeneration. Results showed that the transplanted GMSCs were detected in the bone defects and employed in new bone formation. And the newly formed bone area in mice with GMSCs transplantation was significantly higher than that in control mice. Our findings indicate that systemically transplanted GMSCs can not only home to the mandibular defect but also promote bone regeneration.

Hyperlipidemia compromises homing efficiency of systemically transplanted BMSCs and inhibits bone regeneration.

PURPOSE: Mesenchymal stem cells (MSCs) can selectively home to bone defects and play an essential role in promoting bone regeneration. As an adverse effect factor for bone metabolism, hyperlipidemia significantly impairs bone regeneration. In this study, bone marrow stromal cells (BMSCs) were systemically transplanted into a hyperlipidemic mouse model to explore the effect of hyperlipidemia on stem cell recruitment and bone regeneration. METHODS: Hyperlipidemia was established in ApoE-/- mice (on C57BL/6J background) fed with a high fat diet (HFD) for five weeks. C57BL/6 mice fed with the same diet served as controls. BMSCs labeled with the green fluorescent protein (GFP) were then injected via the tail vein and bone defects were created in the mandibles. The animals were sacrificed at weeks 1, 2 and 4 after surgery, and the fate of the transplanted BMSCs was monitored with a fluorescence microscope and immunohistochemical analysis. After hematoxylin and eosin (HE) staining and Masson's Trichrome (MT) staining, histomorphometric analysis was performed to evaluate bone regeneration. RESULTS: In both groups transplanted with BMSCs, the number of GFP-positive BMSCs detected in the bone defects reached its peak at 1 week after surgery and was decreased thereafter. However, at all time points, less GFP+ cells were detected in the ApoE-/- mice than in the corresponding control mice. BMSCs transplantation significantly enhanced new bone formation, but to a lesser degree in the ApoE-/- mice when compared with the control mice. CONCLUSIONS: Hyperlipidemia compromises homing efficiency of systemically transplanted BMSCs and inhibits bone regeneration.

Effect of umbilical cord mesenchymal stem cell in peri-implant bone defect after immediate implant: an experiment study in beagle dogs.

BACKGROUND: For the sake of reducing post extraction resorption, getting optimal positioning of the implant and shortening treatment time, immediate implant placement following tooth extraction has been proposed as a treatment option. However, the large bone defect peri-implant has a negative influence on the process of bone healing. In this study, umbilical cord mesenchymal stem cells (UCMSCs) were transplanted into the bone defect peri-implant inbeagle dogs and the effect of UCMSCs on bone regeneration in peri-implant were assessed. METHODS: The mandibular second, third and fourth premolars of 8 beagle dogs were extracted bilaterally. The defects in one side were filled with platelet-rich fibrin (PRF) and then UCMSCs were injected into the defect area, while the defects in the other side were filled with PRF only as control group. The titanium implant was placed into the distal root socket of each extracted tooth. The animals were sacrificed at week 2, 4 and 8 post operative. The bone defects adjacent to the implant which are 4 mm in height, 4 mm in the mesio-distal direction and 3.5 mm in the bucco-lingual direction were made after immediate implant. Histomorphometric analysis was performed using methylene blue-fuchsin acid staining and hematoxylin and eosin (HE) staining to evaluate bone regeneration. RESULTS: The direct bone-to-implant contact (BIC) in the experiment after 4 and 8 weeks was 56.47±1.18% and 76.23±2.08%; and in the control group was40.79±0.65% and 61.17±2.79%, respectively. The percentage of newly formed bone after 2, 4 and 8 weeks was 17.60±1.5%, 49.82±4.02% and 67.16±2.1% in experiment group; and in control group 14.30±1.25%, 37.04±2.29% and 58.83±3.36%, respectively. These results represented significant differences statistically. CONCLUSION: Intra-bone marrow injection of UCMSCs can promote new bone formation. UCMSCs can be used to as excellent seed cells to repair the large defect peri-implant after immediate implant.

Effect of umbilical cord mesenchymal stem cell in peri-implant bone defect after immediate implant: an experiment study in beagle dogs.

BACKGROUND: For the sake of reducing post extraction resorption, getting optimal positioning of the implant and shortening treatment time, immediate implant placement following tooth extraction has been proposed as a treatment option. However, the large bone defect peri-implant has a negative influence on the process of bone healing. In this study, umbilical cord mesenchymal stem cells (UCMSCs) were transplanted into the bone defect peri-implant in beagle dogs and the effect of UCMSCs on bone regeneration in peri-implant were assessed. METHODS: The mandibular second, third and fourth premolars of 8 beagle dogs were extracted bilaterally. The defects in one side were filled with platelet-rich fibrin (PRF) and then UCMSCs were injected into the defect area, while the defects in the other side were filled with PRF only as control group. The titanium implant was placed into the distal root socket of each extracted tooth. The animals were sacrificed at week 2, 4 and 8 post operation. The bone defects adjacent to the implant which are 4 mm in height, 4 mm in the mesio-distal direction and 3.5 mm in the bucco-lingual direction were made after immediate implant. Histomorphometric analysis was performed using methylene blue-fuchsin acid staining and hematoxylin and eosin (HE) staining to evaluate bone regeneration. RESULTS: The direct bone-to-implant contact (BIC) in the experiment after 4 and 8 weeks was 56.47 ± 1.18% and 76.23 ± 2.08%; and in the control group was40.79 ± 0.65% and 61.17 ± 2.79%, respectively. The percentage of newly formed bone after 2, 4 and 8 weeks was 17.60 ± 1.5%, 49.82 ± 4.02% and 67.16 ± 2.1% in experiment group; and in control group 14.30 ± 1.25%, 37.04 ± 2.29% and 58.83 ± 3.36%, respectively. These results represented significant differences statistically. CONCLUSION: Intra-bone marrow injection of UCMSCs can promote new bone formation. UCMSCs can be used to as excellent seed cells to repair the large defect peri-implant after immediate implant.