Role and therapeutic perspectives of extracellular vesicles derived from liver and adipose tissue in metabolic dysfunction-associated steatotic liver disease.

The global epidemic of metabolic diseases has led to the emergence of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), which pose a significant threat to human health. Despite recent advances in research on the pathogenesis and treatment of MASLD/MASH, there is still a lack of more effective and targeted therapies. Extracellular vesicles (EVs) discovered in a wide range of tissues and body fluids encapsulate different activated biomolecules and mediate intercellular communication. Recent studies have shown that EVs derived from the liver and adipose tissue (AT) play vital roles in MASLD/MASH pathogenesis and therapeutics, depending on their sources and intervention types. Besides, adipose-derived stem cell (ADSC)-derived EVs appear to be more effective in mitigating MASLD/MASH. This review presents an overview of the definition, extraction strategies, and characterisation of EVs, with a particular focus on the biogenesis and release of exosomes. It also reviews the effects and potential molecular mechanisms of liver- and AT-derived EVs on MASLD/MASH, and emphasises the contribution and clinical therapeutic potential of ADSC-derived EVs. Furthermore, the future perspective of EV therapy in a clinical setting is discussed.

Oxidative Tandem Cyclization of Aromatic Acids with (Benzo)thiophenes: One-Pot Access to Planar Sulfur-Containing Polycyclic Heteroarenes for Lipid-Droplet-Targeted Probes.

The efficient construction of π-conjugated polycyclic heteroarenes represents a significant task in the field of functional materials. A one-step oxidative tandem cyclization of aromatic acids with (benzo)thiophenes was developed to access planar sulfur-containing polycyclic heteroarenes. This protocol undergoes intermolecular cross-dehydrogenative coupling followed by intramolecular Friedel-Crafts acylation and provides a facile pathway to planar polycyclic compounds from inexpensive reactants. The synthesized heteroarenes serving as lipid-droplet-targeted probes exhibit outstanding performance with favorable biocompatibility and photostability.

Exploring the Impact of Coconut Peat and Vermiculite on the Rhizosphere Microbiome of Pre-Basic Seed Potatoes under Soilless Cultivation Conditions.

Soilless cultivation of potatoes often utilizes organic coconut peat and inorganic vermiculite as growing substrates. The unique microbial communities and physicochemical characteristics inherent to each substrate significantly influence the microecological environment crucial for potato growth and breeding. This study analyzed environmental factors within each substrate and employed Illumina sequencing alongside bioinformatics tools to examine microbial community structures, their correlation with environmental factors, core microbial functions, and the dynamics of microbial networks across various samples. These included pure coconut peat (CP1) and pure vermiculite (V1), substrates mixed with organic fertilizer for three days (CP2 and V2), and three combinations cultivated with potatoes for 50 days (CP3, V3, and CV3-a 1:1 mix of coconut peat and vermiculite with organic fertilizer). Vermiculite naturally hosts a more diverse microbial community. After mixing with fertilizer and composting for 3 days, and 50 days of potato cultivation, fungal diversity decreased in both substrates. Coconut peat maintains higher bacterial diversity and richness compared to vermiculite, harboring more beneficial bacteria and fungi, resulting in a more complex microbial network. However, vermiculite shows lower bacterial diversity and richness, with an accumulation of pathogenic microorganisms. Among the 11 environmental factors tested, water-soluble nitrogen (WSN), total nitrogen (TN), available potassium (AK), total organic carbon (TOC) and air-filled porosity (AFP) were significantly associated with microbial succession in the substrate.The nutritional type composition and interaction patterns of indigenous microorganisms differ between vermiculite and coconut peat. Adding abundant nutrients significantly affects the stability and interaction of the entire microbial community, even post-potato cultivation. When using vermiculite for soilless cultivation, precise control and adjustment of nutrient addition quantity and frequency are essential.

Blockade of V-domain immunoglobulin suppressor of T-cell activation reprograms tumour-associated macrophages and improves efficacy of PD-1 inhibitor in gastric cancer.

BACKGROUND AND AIMS: In gastric cancer, the response rate of programmed cell death protein-1 (PD-1) inhibitor is far from satisfactory, indicating additional nonredundant pathways might hamper antitumour immunity. V-domain immunoglobulin suppressor of T-cell activation (VISTA) has been reported in several malignancies as a novel immune-checkpoint. Nevertheless, the role of VISTA in gastric cancer still remains obscure. Our purpose is to explore the clinical significance and potential mechanism of VISTA in affecting gastric cancer patients' survival and immunotherapeutic responsiveness. METHODS: Our study recruited eight independent cohorts with a total of 1403 gastric cancer patients. Immunohistochemistry, multiplex immunofluorescence, flow cytometry or intracellular flow cytometry, quantitative polymerase chain reaction, western blotting, fluorescence-activated cell sorting, magnetic-activated cell sorting, smart-seq2, in vitro cell co-culture and ex vivo tumour inhibition assays were applied to investigate the clinical significance and potential mechanism of VISTA in gastric cancer. RESULTS: VISTA was predominantly expressed on tumour-associated macrophages (TAMs), and indicated poor clinical outcomes and inferior immunotherapeutic responsiveness. VISTA+ TAMs showed a mixed phenotype. Co-culture of TAMs and CD8+ T cells indicated that VISTA+ TAMs attenuated effective function of CD8+ T cells. Blockade of VISTA reprogrammed TAMs to a proinflammatory phenotype, reactivated CD8+ T cells and promoted apoptosis of tumour cells. Moreover, blockade of VISTA could also enhance the efficacy of PD-1 inhibitor, suggesting that blockade of VISTA might synergise with PD-1 inhibitor in gastric cancer. CONCLUSIONS: Our data revealed that VISTA was an immune-checkpoint associated with immunotherapeutic resistance. Blockade of VISTA reprogrammed TAMs, promoted T-cell-mediated antitumour immunity, and enhanced efficacy of PD-1 inhibitor, which might have implications in the treatment of gastric cancer.

In Vitro Study of Thymosin Beta 4 Promoting Transplanted Fat Survival by Regulating Adipose-Derived Stem Cells.

BACKGROUND: Autologous fat grafting (AFG) has emerged as a highly sought-after plastic surgery procedure, although its success has been hampered by the uncertain fat survival rate. Current evidence suggests that adipose-derived stem cells (ADSCs) may contribute to fat retention in AFG. In previous studies, it was confirmed that thymosin beta 4 (Tß4) could enhance fat survival in vivo, although the precise mechanism remains unclear. METHODS: ADSCs were isolated from patients undergoing liposuction and their proliferation, apoptosis, anti-apoptosis, and migration were analyzed under Tß4 stimulation using cell counting kit-8, flow cytometry, wound healing assay, and real-time quantitative PCR. The mRNA levels of genes relating to angiogenesis and Hippo signaling were also determined. RESULTS: Tß4 at 100 ng/mL (p-value = 0.0171) and 1000 ng/mL (p-value = 0.0054) significantly increased ADSC proliferation from day 1 compared to the control group (0 ng/mL). In addition, the mRNA levels of proliferation-associated genes were elevated in the Tß4 group. Furthermore, Tß4 enhanced the anti-apoptotic ability of ADSCs when stimulated with Tß4 and an apoptotic induction reagent (0 ng/mL vs. 1000 ng/mL, p-value = 0.011). Crucially, the mRNA expression levels of angiogenesis-related genes and critical genes in the Hippo pathway were affected by Tß4 in ADSCs. CONCLUSIONS: Tß4 enhances adipose viability in AFG via facilitating ADSC proliferation and reducing apoptosis, and acts as a crucial positive regulator of ADSC-associated angiogenesis. Additionally, Tß4 could be accountable for the phenotypic adjustment of ADSCs by regulating the Hippo pathway. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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 .

Immune inactivation by VISTA predicts clinical outcome and therapeutic benefit in muscle-invasive bladder cancer.

BACKGROUND: V domain Immunoglobulin suppressor of T cell activation (VISTA) has been proved to be a novel immune checkpoint molecule that positively regulates T cell infiltration in several malignancies. However, the clinical impact of VISTA on muscle-invasive bladder cancer (MIBC) patients remains relatively obscure. METHODS: This study enrolled 135 MIBC patients from Zhongshan Hospital (ZSHS) and 391 patients from The Cancer Genome Atlas (TCGA) to examine the VISTA expression and immune contexture based on immunohistochemistry (IHC) staining and CIBERSORT algorithm. Additionally, IMvigor210 Cohort included 195 bladder-derived urothelial carcinoma patients to evaluate the efficacy of immunotherapy. Kaplan-Meier curve and Cox regression analyses were conducted to assess clinical outcomes. RESULTS: MIBC patients with high VISTA+ immune cells (ICs) possessed poor overall survival and inferior therapeutic responsiveness to adjuvant chemotherapy (ACT), but superior responsiveness to PD-L1 inhibitor. VISTA+ ICs infiltration shaped an immunoevasive context featured by regulatory T cells (Tregs), M2 macrophages, mast cells and exhausted CD8+ T cells infiltration, with increased interleukin 10 (IL-10), transforming growth factor-ß (TGF-ß) and interferon-γ (IFN-γ), but also elevated T-cell immunoglobulin mucin-3 (TIM-3), lymphocyte activation gene 3 (LAG-3) and T-cell immunoglobulin and ITIM domain (TIGIT), which was also mainly presented in basal-squamous and luminal-infiltrated subtypes of MIBC. CONCLUSION: VISTA+ ICs infiltration could be an independent predictor to identify poor prognosis and therapeutic responses (PD-L1 blockade and ACT) in MIBC patients, which was associated with immunoevasive contexture. The novel immune checkpoint VISTA might be utilized as a candidate treatment biomarker in MIBC patients.

The preliminary study of exosomes derived from thymosin beta 4-treated adipose-derived stem cells in fat grafting.

BACKGROUND: The retention rate in autologous fat grafting is an increasing concern for surgeons and patients. Our previous research verified that thymosin beta 4 (Tß4) positively affected fat survival, while the mechanism was unknown. The endothelial cells (ECs) and exosomes derived from adipose-derived stem cells (ADSCs) were regarded to play a critical role in fat transplantation. OBJECTIVE: This study aimed to evaluate the effect of exosomes derived from Tß4-treated ADSCs on EC proliferation and to identify the exosomal microRNA (miRNA) profile compared with the Tß4-untreated group. Additionally, this research intended to recognize the related molecules and signaling pathways in the Tß4-treated group with potential roles in fat transplants. METHODS: ADSCs were collected from patients who underwent liposuction surgery. Depending on whether the medium was supplemented with exogenous Tß4 or not, exosomes derived from cultured ADSCs were divided into the Tß4-Exos group and Con-Exos group. Exosome uptake and cell counting kit-8 (CCK-8) assays assessed the influence of Tß4-Exos on EC proliferation. The exosomal miRNAs of the two groups were analyzed by next-generation sequencing. With the criteria at the |log2 (fold change)| ≥ 1 and p-value < 0.05, up-regulated and down-regulated differentially expressed miRNAs (DEMs) were obtained. Prediction databases were used to predict the downstream mRNAs for DEMs. And then, overlapping genes for the up-regulated DEMs and the down-regulated were screened out, followed by enrichment analysis, protein-protein interaction network construction, and the gene cluster and hub gene identification. RESULTS: ADSCs were obtained from four female patients. The exosome uptake and CCK-8 assays showed that the Tß4-Exos could increase cell growth rate compared with the control group (DMEM-H + PBS). In Tß4-Exos and Con-Exos groups, 2651 exosomal miRNAs were recognized, with 80 up-regulated and 99 down-regulated DEMs according to the criteria. After the prediction, 621 overlapping genes for the up-regulated and 572 for the down-regulated DEMs were screened. The subsequent bioinformatics analysis found specific molecules and pathways related to the positive effect on fat survival. CONCLUSIONS: The exosomes derived from Tß4-treated ADSCs probably positively affect EC proliferation. Compared with the Con-Exos group, several exosomal DEMs, genes, and pathways were distinguished. These findings of this exploratory study provide the potential direction for future in-depth research on fat grafting.

Manual Lymphatic Drainage for Breast Cancer-related Lymphedema: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: The purpose of this systematic review was to meta-analyze the effectiveness of manual lymphatic drainage (MLD) in breast cancer-related lymphedema (BCRL) patients. METHODS: The following databases: the Cochrane Library, the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Web of Science, ClinicalTrials.gov were systematically searched. All English publications before April 2021 have been retrieved without any restrictions of countries, time, or article type. We included randomized controlled trials (RCTs) examining the effectiveness of MLD versus control group without MLD of women with BCRL. The outcomes were (1) the incidence of lymphedema, (2) volumetric changes of lymphedema, (3) pain, (4) quality of life. Review Manager 5.3 was used to perform statistical analysis. RESULTS: In total, 11 RCTs involving 1564 patients were included, in which 10 trials were deemed viable for inclusion in the meta-analysis. Due to the effects of MLD for BCRL, statistically significant improvements were found on the incidence of lymphedema (RR = 0.58, 95% CI [0.37, 0.93], P =.02) and pain intensity (SMD = -0.72, 95% CI [-1.34, -0.09], P = .02). Besides, the meta-analysis carried out implied that the effects that MLD had on volumetric changes of lymphedema and quality of life, were not statistically significant. CONCLUSION: The current evidence based on the RCTs shows that pain of BCRL patients undergoing MLD is significantly improved, while our findings do not support the use of MLD in improving volumetric of lymphedema and quality of life. Note that the effect of MLD for preventing BCRL is worthy of discussion.

The Value of BMI for Breast Reconstructions with the SIEA Flaps: Predicting the Ideal Intercostal Plane for the End-to-End Microvascular Anastomosis and the Possibility of Utilizing the TDA as a Salvage Recipient Choice.

BACKGROUND: The superficial inferior epigastric artery (SIEA) diameter and the matching degree between the donor and the recipient arteries in terms of diameter are key factors affecting the outcome of the procedure in breast reconstructions with the SIEA flaps. A diameter of the SIEA ≥ 1.5 mm and a matching degree ≥ 1:2 (50%) of the diameters of the donor and the recipient arteries are recognized standards for the SIEA and the internal mammary artery (IMA) to achieve an end-to-end anastomosis. However, further refinements of the population characteristics and the ideal microscopic anastomosis intercostal planes are currently lacking for the criteria. METHODS: In this study, based on 20 sides of hemiabdomen with computed tomography angiography (CTA) data suggesting the presence of the SIEA, we analysed the diameters of the donor and the recipient arteries as well as their matching degrees. The correlations between the parameters above and body mass index (BMI) were assessed. Based on the lower bounds of the 95% confidence intervals of the matching degrees and the two critical nodes of 50% and 67%, we theoretically evaluated the possibility of an end-to-end anastomosis of the SIEA and the IMA at different levels of BMIs and intercostal spaces, and predicted the possible intraoperative management measures for the SIEA. RESULTS: The SIEA diameter, the thoracodorsal artery (TDA) diameter, and the diameters of the IMA at the 2nd to the 5th intercostal levels were positively correlated with the BMI (p < 0.05). A value of BMI ≥ 24 kg/m2 could indirectly reflect the application premise of the diameter of the SIEA ≥ 1.5 mm. The matching degrees of the SIEA with the TDA or the IMA at the 2nd to the 5th intercostal level were linearly and positively correlated with the BMI (p < 0.001). Based on the confidence interval analysis, we predicted different management techniques that might be needed intraoperatively for the SIEA at different BMI levels, when the SIEA and the IMA or the TDA were to be anastomosed in an end-to-end way. CONCLUSION: For patients with preoperative CTA data suggesting the presence of the SIEA in the second-stage breast reconstructions, when a value of BMI ≥ 24 kg/m2 is met, the SIEA and the IMA can theoretically achieve an end-to-end anastomosis at the 3rd to the 5th intercostal level, and when 24 kg/m2 ≤ BMI ≤ 25 kg/m2, due to the large difference in diameters, the SIEA and the IMA at the 2nd intercostal level might need to adopt an end-to-side anastomosis or switch to the TDA recipient site. Based on this study's findings and aesthetic effect considerations, we think that the 3rd and the 4th intercostal planes are ideal choices for the end-to-end anastomosis. As a salvage recipient option, the TDA can theoretically achieve an end-to-end anastomosis with the SIEA at a value of BMI ≥ 24 g/m2. LEVEL OF EVIDENCE IV: 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 .

Prediction of the Postoperative Fat Volume Retention Rate After Augmentation Mammoplasty with Autologous Fat Grafting: From the Perspective of Preoperative Inflammatory Level.

BACKGROUND: Postoperative fat volume retention rate (PFVRR) after augmentation mammoplasty with autologous fat grafting is highly variable on an individual basis and challenging to be predicted. However, at present, there is a lack of further research on the relevant preoperative patient's self-related influencing factors. The early inflammatory response degree, directly influenced by preoperative inflammatory level, is an indispensable part of angiogenesis, which is a key factor in adipocyte survival. METHODS: A retrospective review was conducted of patients who underwent breast augmentation with autologous fat grafting performed by a senior surgeon. Preoperative patient demographics and laboratory findings relevant to inflammatory level, such as monocyte to lymphocyte ratio (MLR), were included as the independent variables. The PFVRR more than 3 months after the operation was included as the dependent variable. Key factors influencing the PFVRR were analyzed. RESULTS: Sixty-three patients were included. The total volume of bilateral fat injection was 375.00 (range, 320.00-400.00) mL, and the long-term bilateral volumetric change was 106.98 (range, 69.90-181.58) mL. The mean PFVRR was 35.36% ± 15.87%, and the preoperative MLR was an independent positive influencing factor of it, while the lymphocyte (L) count was negative. By ROC curve analysis, a value of MLR equal to 0.23 was the diagnostic cut-off point for whether PFVRR was greater than 50%, and its area under the curve was 0.870, with a sensitivity of 93.33% and a specificity of 81.25%. The other hematological parameters and demographics such as age, body mass index, and donor site were not significantly correlated with the PFVRR. CONCLUSION: Preoperative peripheral blood inflammatory indicators can influence the PFVRR, with the MLR positively and L count negatively. Based on the diagnostic threshold of MLR = 0.23 derived from this study, clinicians can make reasonable predictions of whether half of the injected fat volume would be retained based on preoperative blood routine tests that are readily available. LEVEL OF EVIDENCE IV: 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 .

An Intraoperative Measurement Method of Breast Symmetry Using Three-Dimensional Scanning Technique in Reduction Mammaplasty.

BACKGROUND: Intraoperative symmetrical assessment plays a decisive role in the aesthetic results of reduction mammaplasty, but it depends mostly on the surgeons' experience that may be biased by individual subjective factors. This study was intended to propose an objective method based on a hand-held three-dimensional (3D) scanner to assist intraoperative symmetrical assessment, aiming to achieve better aesthetic results in reduction mammaplasty. METHODS: Sixty patients were enrolled in the study from April 2018 to January 2020. Intraoperative 3D scanning was routinely performed on 29 patients (study group) to assist symmetrical adjustments during breast shaping. 3D surface scanning data of both groups were obtained at 3 months postoperatively to objectively assess breast symmetry. Postoperative symmetry scores in five aspects, including nipple-areolar complex position, inframammary-fold height, breast size, shape, and footprint, were rated by six independent observers based on anonymized photographs to subjectively evaluate pre- and postoperative breast symmetry of the two groups. RESULTS: The bilateral breast volume difference of the study group was significantly smaller than the control group (39.1 vs. 113.3 cm3, p = 0.001), as well as the difference in nipple to inframammary-fold distance (2.79 vs. 7.43 mm, p = 0.01). The observer-reported results showed that breast reduction significantly improved postoperative symmetry in all five aspects compared with preoperative symmetry in the study group (P<0.001). Furthermore, postoperative symmetrical ratings of all five aspects in the study group were statistically better than the control group (P<0.05). CONCLUSIONS: Intraoperative 3D scanning provided a reliable method to assist symmetry adjustments and ensure better postoperative breast symmetry in reduction mammaplasty. LEVEL OF EVIDENCE IV: 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 .

Endoscopic subcutaneous mastectomy plus liposuction via a single axillary incision for gynecomastia in Asian patients: A report of 45 cases.

BACKGROUND: Most techniques for surgical correction of gynecomastia are performed by anterior and/or lateral chest incisions, showing an "operated" appearance. Our initial experience was introduced in gynecomastia with a combination of endoscopic subcutaneous mastectomy and liposuction via an axillary single incision. METHODS: Between September 2018 and July 2019, a series of 45 male patients who had Simon grade I or II gynecomastia were enrolled in this study. The demographics, operative data, and postoperative complications were recorded in detail. Four independent observers gave their ratings by assigning scores of 1 to 5 for 6 main aesthetic aspects based on pre and postoperative photographs. RESULTS: Endoscopic subcutaneous mastectomy combined with liposuction via an axillary single incision was performed successfully in all cases. Mean operative duration was 82.6 minutes for each side (37.5-132.5 minutes). The weight of the resected glandular tissue of the 89 breasts was 26 to 130 g and the aspiration volume was 60 to 700 mL. Three unilateral subcutaneous seromas (3.3%), 5 unilateral hematomas (5.6%), and 1 bilateral minimal skin redundancy (2.2%) were encountered. Observer-reported outcomes indicated that patients with grade Ⅰ gynecomastia had significantly better aesthetic results than those with grade Ⅱb in the aspects of symmetry, shape of nipple, shape of areola, contour regularity, and overall appearance (P < .001). Patients with grade Ⅱa gynecomastia also witnessed better improvement than grade Ⅱb in shape of nipple, contour regularity, and overall appearance (P < .05). CONCLUSION: Endoscopic subcutaneous mastectomy combined with liposuction via an axillary single incision is a feasible minimally invasive technique for the treatment of gynecomastia. The combined method is effective in achieving satisfied aesthetic results for Simon grades I and Ⅱa gynecomastia, and it can also be an alternative choice for grade Ⅱb.

Postoperative Health-related Quality of Life in Reduction Mammaplasty: A Systematic Review and Meta-Analysis.

BACKGROUND: Breast hypertrophy is a chronic health problem. Until now, reduction mammaplasty is still a critical treatment for this disease. Given the publications, which reviewed the relationship between operation and quality of life, based on nonrandomized controlled studies and how low their quality are. Thus, we aimed to assess the effectiveness of reduction mammaplasty in improving health-related quality of life based on high-quality randomized-controlled trials. METHOD: A systematic search of the following databases: PubMed (MEDLINE), the Cochrane Library, the Cochrane Central Register of Controlled Trials, Web of Science, EMBASE, ClinicalTrials.gov, BIOSIS previews, and GreyNet. All the English publications have been searched without any restrictions of time, countries, or article type. Studies examining the effects of breast reduction versus control group on postoperative quality of life were included. Data on studies, patient characteristics, outcome measures were extracted. Statistical analysis was performed using Review Manager 5.3. RESULTS: In all, 7 randomized-controlled trials involving 285 participants were included, in which 4 studies were pooled in the meta-analysis. Because of the effect of reduction mammaplasty, statistically significant improvements were found on pain (standardised mean difference [SMD], -1.29; 95% confidence interval [CI], -1.63 to -0.96; P < 0.00001), physical function (SMD, 0.97; 95% CI, 0.69-1.25; P < 0.00001) and psychological function (SMD, -0.79; 95% CI, -1.07 to -0.52; P < 0.00001). CONCLUSIONS: Our findings based on the randomized-controlled trials suggest that the quality of life of women undergoing breast reduction surgery is significantly improved. Reduction mammaplasty is an effective treatment for symptomatic breast hypertrophy.

Predicting the Feasibility of Utilizing SIEA Flap for Breast Reconstruction with Preoperative BMI and Computed Tomography Angiography (CTA) Data.

BACKGROUND: Diameters greater than 1.5 mm are considered one of the generally accepted criteria for utilizing superficial epigastric artery (SIEA) flaps for breast reconstruction. However, this standard fails to consider individual differences among patients or deep inferior epigastric perforator (DIEP) perfusion of the same angiosome as the SIEA. This study combined the SIEA system with the DIEP system and explored the relationship between the two systems and body mass index (BMI) to theoretically provide a reference for flap choice in the preoperative surgical plan. METHODS: This study analysed preoperative computed tomography angiography (CTA) data from patients who received systematically postoperative treatment for unilateral breast cancer and were scheduled for breast reconstruction from 2013 to 2018 in our centre. All patients included had no past medical history that might have influenced the diameter of the SIEA, and their CTA data showed the presence of SIEA. RESULTS: Twenty-five females with a mean BMI of 23.6 ± 3.3 kg/m2 were included. A total of 30 hemi-abdomens identified with the SIEA were assessed. The measured mean diameter of the SIEA was 1.63 ± 0.55 mm, showing a highly linear correlation with BMI (r = 0.73, p < 0.001), while the maximum diameter of the deep inferior epigastric perforator (DIEPmax) and the number of dominant perforators originating from the deep inferior epigastric artery (DIEA) were not related to BMI. It was analysed from the equation between the calibre of the SIEA and BMI that when the BMI was greater than or equal to 24 kg/m2, the minimum diameter of the SIEA was at least 1.5 mm; when the BMI was 25 kg/m2, the diameter of the SIEA was, at most, 2.0 mm. Based on the linear correlation described above, we proposed that if the diameter of the SIEA was greater than or equal to 2.0 mm, a BMI ≥ 25 kg/m2 could be fully guaranteed. In terms of the advantageous single pedicle for reconstruction, the ratio of the SIEA diameter to DIEPmax (SIEA/DIEPmax) showed a significant linear correlation with BMI (r = 0.82, p < 0.001), and when the BMI was greater than or equal to 25 kg/m2, the lower limit of its predicted value was above 1.0; in other words, the SIEA diameter was advantageous compared with DIEPmax for the use of a single pedicle. In terms of perfusion, the SIEA system was positively correlated with BMI (p < 0.001), while the DIEP system was not. The difference in perfusion level between the SIEA and DIEP systems showed a positive correlation with BMI (p = 0.001), while the sum of the two systems only tended to be correlated, without statistical significance (p = 0.06). CONCLUSIONS: For patients with a BMI ≥ 25 kg/m2 or an SIEA diameter ≥ 2.0 mm, application of an SIEA flap is theoretically a preferable choice in preoperative surgical planning for breast reconstruction. And the patients should meet two conditions: the first one is the absence of past medical history that might potentially influence the diameter of the SIEA; the second is the presence of the SIEA, which has already been shown by the preoperative imaging data. Through perfusion-related studies, we propose that the SIEA is likely a compensatory vessel that is inclined to present in people with larger BMIs. LEVEL OF EVIDENCE IV: 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 .

Therapeutic potential of human minor salivary gland epithelial progenitor cells in liver regeneration.

Liver disease is a serious problem affecting millions of people with continually increasing prevalence. Stem cell therapy has become a promising treatment for liver dysfunction. We previously reported on human minor salivary gland mesenchymal stem cells (hMSGMSCs), which are highly self-renewable with multi-potent differentiation capability. In this study, keratinocyte-like cells with self-regeneration and hepatic differentiation potential were isolated and characterized, and named human minor salivary gland epithelial progenitor cells (hMSG-EpiPCs). hMSG-EpiPCs were easily obtained via minor intraoral incision; they expressed epithelial progenitor/stem cell and other tissue stem cell markers such as CD29, CD49f, cytokeratins, ABCG2, PLET-1, salivary epithelial cell markers CD44 and CD166, and the Wnt target related gene LGR5 and LGR6. The cells were induced into functional hepatocytes in vitro which expressed liver-associated markers ALB, CYP3A4, AAT, and CK18. Upon transplantation in vivo, they ameliorated severe acute liver damage in SCID mice caused by carbon tetrachloride (CCl4) injection. In a two-thirds partial hepatectomy mouse model, the transplanted cells survived at least 4 weeks and exhibited hepatic potential. These findings demonstrate that hMSG-EpiPCs have potential as a cellular therapy basis for hepatic diseases, physiological and toxicology studies and regenerative medicine.

Characterization of a Self-renewing and Multi-potent Cell Population Isolated from Human Minor Salivary Glands.

Adult stem cells play an important role in maintaining tissue homeostasis. Although these cells are found in many tissues, the presence of stem cells in the human minor salivary glands is not well explored. Using the explant culture method, we isolated a population of cells with self-renewal and differentiation capacities harboring that reside in the human minor salivary glands, called human minor salivary gland mesenchymal stem cells (hMSGMSCs). These cells show embryonic stem cell and mesenchymal stem cell phenotypes. Our results demonstrate that hMSGMSCs have the potential to undergo mesodermal, ectodermal and endodermal differentiation in conditioned culture systems in vitro. Furthermore, in vivo transplantation of hMSGMSCs into SCID mice after partial hepatectomy shows that hMSGMSCs are able to survive and engraft, characterized by the survival of labeled cells and the expression of the hepatocyte markers AFP and KRT18. These data demonstrate the existence of hMSGMSCs and suggest their potential in cell therapy and regenerative medicine.