Association of glucagon-like peptide-1 receptor agonists with risk of cancers-evidence from a drug target Mendelian randomization and clinical trials.

BACKGROUND: Glucagon-like peptide-1 receptor (GLP1R) agonists have been approved by Food and Drug Administration for management of obesity. However, the causal relationship of GLP1R agonists (GLP1RA) with cancers still unclear. METHODS: The available cis-eQTLs for drugs target genes (GLP1R) were used as proxies for exposure to GLP1RA. Mendelian randomizations (MR) were performed to reveal the association of genetically-proxied GLP1RA with 14 common types cancer from large-scale consortia. Type 2 diabetes was used as positive control, and the GWASs data including 80 154 cases and 853 816 controls. Replicating the findings in the FinnGen study and then pooled with meta-analysis. Finally, all the related randomized controlled trails (RCTs) on GLP1RA were systematically searched from PubMed, Embase, and the Cochrane Library to comprehensively synthesize the evidence to validate any possible association with cancers. RESULT: A total of 22 significant cis-eQTL single-nucleotide polymorphisms were included as genetic instrument. The association of genetically-proxied GLP1RA with significantly decreased type 2 diabetes risk [OR (95%)=0.82 (0.79-0.86), P<0.001], which ensuring the effectiveness of identified genetic instruments. The authors found favorable evidence to support the association of GLP1RA with reduced breast cancer and basal cell carcinoma risk [0.92 (0.88-0.96), P<0.001, 0.92 (0.85-0.99), P=0.029, respectively], and with increased colorectal cancer risk [1.12 (1.07-1.18), P<0.001]. In addition, there was no suggestive evidence to support the association of GLP1RA with ovarian cancer [0.99 (0.90-1.09), P=0.827], lung cancer [1.01 (0.93-1.10), P=0760], and thyroid cancer [0.83 (0.63-1.10), P=0.187]. Our findings were consistent with the meta-analysis. Finally, 80 RCTs were included in the systematic review, with a low incidence of different kinds of cancer. CONCLUSIONS: Our study suggests that GLP1RA may decrease the risk of breast cancer and basal cell carcinoma, but increase the risk of colorectal cancer. However, according to the systematic review of RCTs, the incidence of cancer in patients treated with GLP1RA is low. Larger sample sizes of RCTs with long-term follow-up are necessary to establish the incidence of cancers and evaluate the risk-benefit ratios.

The prevalence, complications, and risk factors for infantile hemangioma: a systematic review and meta-analysis.

The epidemiological landscape of infantile hemangioma (IH) has been extensively explored through diverse data sources; however, a scarcity of systematically pooled and quantified evidence from comprehensive global studies persists. In this meta-analysis, we systematically review available literature to elucidate the prevalence, distribution of lesions, complications, and risk factors associated with IH. A meticulous search encompassing the Cochrane Library, PubMed, Embase, and Web of Science identified 3206 records, of which 55 studies met the inclusion criteria. We found that the overall prevalence of IH is 2.8% [95% confidence interval (CI): 1.5-4.4%] (31,274,396 infants), and IH was located more frequently in the head and neck with a prevalence of 47.4% (95% CI: 39.5-55.4%). The overall prevalence of complications of IH is 24.3% (95% CI: 18.6-30.5%), ulceration is 16.0% (95% CI: 10.4-21.2%), bleeding is 5.6% (95% CI: 3.3-8.5%), visual impairment is 5.6% (95% CI: 3.0-8.9%), infection is 2.8% (95% CI: 1.5-4.8%), subglottic obstruction is 1.5% (95% CI: 0.5-3.0%), respectively. Through 27 studies, we have evaluated 35 factors encompassing perinatal factors, socioeconomic factors, maternal complications, drug factors, and antepartum procedures, and identified 18 risk factors that increase the prevalence of IH. These findings can greatly assist clinicians and family members in effectively evaluating the risk of IH, and determining whether pregnant women should undergo intensified monitoring or preventive measures.

Validating Operating Stability and Biocompatibility Toward Safer Zinc-Based Batteries.

Wearable and implantable electronics are standing at the frontiers of science and technology, driven by the increasing demands from modernized lifestyles. Zinc-based batteries (ZBs) are regarded as ideal energy suppliers for these biocompatible electronics, but the corresponding biocompatibility validation is still in the initial stage. Meanwhile, complicated working conditions and some extreme electrolyte environments raise strict challenges, leaving less choices for safe ZBs. Toward higher operating stability and biocompatibility, this work proposes a hydrogel electrolyte featuring the moisture maintaining ability and a robust interface, which could further provide a milder environment for Zn-MnO2 batteries and Zn-air batteries. The cytotoxicity and tissue injury of batteries are evaluated with human cell lines and battery implantations on the animal models, which demonstrate the high biocompatibility of ZBs, while preliminary wearable devices implementation further verifies their operating stability. This work may provide a pathway for developing and validating biocompatible ZBs, contributing to their future practical employment in relevant fields.

Peripheral Blood CD8+T Cell as a Prognostic Biomarker for Hospitalised COVID-19 Patients Without Antiviral Treatment.

Background: The status of T lymphocyte subset counts in patients with COVID-19 remains uncertain. This study aimed to assess alterations in peripheral blood CD3+CD8+T (CD8+T) cells among hospitalized COVID-19 patients who have not received antiviral treatment and to evaluate their prognostic value within this patient population. Methods: A single-center, retrospective cohort study and a meta-analysis were conducted. The cohort study was performed at Xiangya Hospital from December 5, 2022, to January 31, 2023. We conducted a meta-analysis to explore the association between peripheral blood CD3+CD8+T cells and mortality in COVID-19 patients who did not receive antiviral therapy. All relevant studies in Embase, PubMed, Web of Science databases were systematically searched for meta-analysis. Results: The retrospective cohort study included 201 patients. A significant decrease in peripheral blood CD8+ T cell count was found to be associated with an increased risk of mortality (adjusted odds ratio [aOR]: 13.88; 95% confidence interval [CI]: 3.15-61.23), after adjusting for gender, age, comorbidities, severity at admission, steroid therapy, and antibiotic therapy. The threshold value for CD8+T cell counts, determined by the receiver operating characteristic (ROC) curve analysis, was 145.5 (area under the curve [AUC]: 0.828, specificity: 90.3%, sensitivity: 72.9%, P<0.001). Additionally, A total of 7 studies with 2765 participants were included in the meta-analysis. The meta-analysis reveals a significant association between lower CD8+ T cell counts and mortality (odds ratio [OR] = 3.543, 95% CI: 1.726 to 7.272; I2=93%). Conclusion: Peripheral blood CD8+ T cell can serve as a valuable prognostic biomarker for hospitalized patients who do not receive antiviral treatment.

High glucose environment induces NEDD4 deficiency that impairs angiogenesis and diabetic wound healing.

BACKGROUND: Healing of diabetic wounds, characterized by impaired angiogenesis, remains a clinical challenge. E3 ligase have been identified as potential therapeutic targets of wound healing. OBJECTIVE: We assessed the role of E3 ligase NEDD4 in the context of angiogenesis and diabetic wound healing. METHODS: The mRNA expression levels of NEDD4, TSP1 and VEGF were determined by real-time PCR. Western blotting was used to evaluate the protein expression of NEDD4, TSP1 and VEGF. The ubiquitination of TSP1 was evaluated by immunoprecipitation. MTT assay, wound healing assay and tube formation assay were performed to assess the proliferation, migration and angiogenic functions of endothelial cells. The epigenetic modification in the promoter of NEDD4 was confirmed using BSP assay and ChIP-qPCR assay. The role of NEDD4 in wound healing was further verified in diabetic mouse model. RESULTS: NEDD4 promotes proliferation, migration and tube formation of endothelial cells. It binds to and ubiquitinates TSP1, which lead to TSP1 degradation and thus increased VEGF expression. The inhibitory effect of NEDD4 silencing on the angiogenesis ability of endothelial cells can be restored by TSP1 knockdown. NEDD4 is reduced in diabetic patients, which may due to hypermethylation of NEDD4 promoter mediated via DNMT1 under high glucose condition. Furthermore, inhibition of NEDD4 represses wound healing in diabetic mouse model. CONCLUSION: NEDD4 might promote angiogenesis and wound healing by inhibiting TSP1 via ubiquitination in diabetic patients.

HI-MViT: A lightweight model for explainable skin disease classification based on modified MobileViT.

Objective: To develop an explainable lightweight skin disease high-precision classification model that can be deployed to the mobile terminal. Methods: In this study, we present HI-MViT, a lightweight network for explainable skin disease classification based on Modified MobileViT. HI-MViT is mainly composed of ordinary convolution, Improved-MV2, MobileViT block, global pooling, and fully connected layers. Improved-MV2 uses the combination of shortcut and depth classifiable convolution to substantially decrease the amount of computation while ensuring the efficient implementation of information interaction and memory. The MobileViT block can efficiently encode local and global information. In addition, semantic feature dimensionality reduction visualization and class activation mapping visualization methods are used for HI-MViT to further understand the attention area of the model when learning skin lesion images. Results: The International Skin Imaging Collaboration has assembled and made available the ISIC series dataset. Experiments using the HI-MViT model on the ISIC-2018 dataset achieved scores of 0.931, 0.932, 0.961, and 0.977 on F1-Score, Accuracy, Average Precision (AP), and area under the curve (AUC). Compared with the top five algorithms of ISIC-2018 Task 3, Marco's average F1-Score, AP, and AUC have increased by 6.9%, 6.8%, and 0.8% compared with the suboptimal performance model. Compared with ConvNeXt, the most competitive convolutional neural network architecture, our model is 5.0%, 3.4%, 2.3%, and 2.2% higher in F1-Score, Accuracy, AP, and AUC, respectively. The experiments on the ISIC-2017 dataset also achieved excellent results, and all indicators were better than the top five algorithms of ISIC-2017 Task 3. Using the trained model to test on the PH2 dataset, an excellent performance score is obtained, which shows that it has good generalization performance. Conclusions: The skin disease classification model HI-MViT proposed in this article shows excellent classification performance and generalization performance in experiments. It demonstrates how the classification outcomes can be applied to dermatologists' computer-assisted diagnostics, enabling medical professionals to classify various dermoscopic images more rapidly and reliably.

GelMA-based bioactive hydrogel scaffolds with multiple bone defect repair functions: therapeutic strategies and recent advances.

Currently, the clinical treatment of critical bone defects attributed to various causes remains a great challenge, and repairing these defects with synthetic bone substitutes is the most common strategy. In general, tissue engineering materials that mimic the structural, mechanical and biological properties of natural bone have been extensively applied to fill bone defects and promote in situ bone regeneration. Hydrogels with extracellular matrix (ECM)-like properties are common tissue engineering materials, among which methacrylate-based gelatin (GelMA) hydrogels are widely used because of their tunable mechanical properties, excellent photocrosslinking capability and good biocompatibility. Owing to their lack of osteogenic activity, however, GelMA hydrogels are combined with other types of materials with osteogenic activities to improve the osteogenic capability of the current composites. There are three main aspects to consider when enhancing the bone regenerative performance of composite materials: osteoconductivity, vascularization and osteoinduction. Bioceramics, bioglass, biomimetic scaffolds, inorganic ions, bionic periosteum, growth factors and two-dimensional (2D) nanomaterials have been applied in various combinations to achieve enhanced osteogenic and bone regeneration activities. Three-dimensional (3D)-bioprinted scaffolds are a popular research topic in bone tissue engineering (BTE), and printed and customized scaffolds are suitable for restoring large irregular bone defects due to their shape and structural tunability, enhanced mechanical properties, and good biocompatibility. Herein, the recent progress in research on GelMA-based composite hydrogel scaffolds as multifunctional platforms for restoring critical bone defects in plastic or orthopedic clinics is systematically reviewed and summarized. These strategies pave the way for the design of biomimetic bone substitutes for effective bone reconstruction with good biosafety. This review provides novel insights into the development and current trends of research on GelMA-based hydrogels as effective bone tissue engineering (BTE) scaffolds for correcting bone defects, and these contents are summarized and emphasized from various perspectives (osteoconductivity, vascularization, osteoinduction and 3D-bioprinting). In addition, advantages and deficiencies of GelMA-based bone substitutes used for bone regeneration are put forward, and corresponding improvement measures are presented prior to their clinical application in near future (created with BioRender.com).

The value of cuproptosis-related differential genes in guiding prognosis and immune status in patients with skin cutaneous melanoma.

Background: Skin cutaneous melanoma (SKCM) is one of the most common cutaneous malignancies, which incidence is increasing. Cuproptosis is a new type of programming cell death recently reported, which may affect the progression of SKCM. Method: The mRNA expression data of melanoma were obtained from the Gene Expression Omnibus and the Cancer Genome Atlas databases. We constructed a prognostic model according to the cuproptosis-related differential genes in SKCM. Finally, real-time quantitative PCR was performed to verify the expression of cuproptosis-related differential genes in patients with different stages of cutaneous melanoma. Results: We detected 767 cuproptosis-related differential genes based on 19 cuproptosis-related genes, and screened out 7 differential genes to construct a prognostic model, which including three high-risk differential genes (SNAI2, RAP1GAP, BCHE), and four low-risk differential genes (JSRP1, HAPLN3, HHEX, ERAP2). Kaplan-Meier analysis indicated that SKCM patients with low-risk differential genes signals had better prognosis. The Encyclopedia of Genomes results manifested that cuproptosis-related differential genes are not only involved in T cell receptor signaling channel, natural killer cell mediated cytotoxicity, but also chemokine signaling pathway and B cell receptor signaling pathway. In our risk scoring model, the receiver operating characteristic (ROC) values of the three-time nodes are 0.669 (1-year), 0.669 (3-year) and 0.685 (5-year), respectively. Moreover, the tumor burden mutational and immunology function, cell stemness characteristics and drug sensitivity have significant differences between low-risk group and high-risk group. The mRNA level of SNAI2, RAP1GAP and BCHE in stage Ⅲ+Ⅳ SKCM patients was significantly higher than that in stage Ⅰ+Ⅱ patients, while the level of JSRP1, HAPLN3, HHEX and ERAP2 in stage Ⅰ+Ⅱ SKCM patients was more remarkable higher than that in stage Ⅲ+Ⅳ SKCM patients. Conclusion: In summary, we suggest that cuproptosis can not only regulate the tumor immune microenvironment but also affect the prognosis of SKCM patients, and may offer a basic theory for SKCM patients survival studies and clinical decision-making with potentially therapeutic drugs.

Efficacy and Safety of Photodynamic Therapy for the Treatment of Actinic Keratoses: A Meta-Analysis Update of Randomized Controlled Trials.

BACKGROUND: Actinic keratoses (AKs) are common and some may evolve into squamous cell carcinoma. Photodynamic therapy (PDT), imiquimod, cryotherapy, and other methods have been reported to have good effects. However, which treatment is the most effective with the best cosmetic results and fewest complications is uncertain. OBJECTIVE: To evaluate which method has the best efficacy and cosmetic results with less adverse events and recurrence rate. MATERIALS AND METHODS: All relevant articles up to July 31, 2022 were searched from Cochrane, Embase, and PubMed databases. Extract and analyze the data of efficacy, cosmetic results, local reactions, and adverse effects. RESULTS: Twenty-nine articles with 3,,850 participants and 24,747 lesions were included. Quality of evidence was generally high. The efficacy of PDT was better in complete response (CR) (lesions CR; risk ratio (RR) 1.87; 95% confidence interval (CI) 1.55-1.87/patient CR; RR 3.07; 95% CI 2.07-4.56), overall preference, and cosmetic results. The time cumulative meta-analysis showed that the curative effect was gradually increasing before 2004, and then gradually stabilizing. Two groups showed no statistically significant differences in recurrence. CONCLUSION: Compared with other methods, PDT is significantly more effective for AK with excellent cosmetic results and reversible adverse effects.

"Less is better-Full-incision double-eyelid blepharoplasty with rapid recovery".

SUMMARY: Full-incision double eyelid blepharoplasty is effective, but its postoperative complications, such as local trauma and persistent tissue swelling, are major concerns for patients. Since tissue swelling is caused by the obstruction of blood and lymphatic flow, the authors modified the conventional full-incision method by minimizing the trauma as much as possible. Twenty-five patients underwent the modified procedure. There was minor swelling immediately after the surgery, which subsided 1-5 days after the surgery. No patient reported loss of the double eyelid crease. Only 2 patients underwent a second operation due to a low crease. The satisfactory ratio was 92% (23 of 25). According to our understanding of this technique, LESS trauma is the key to obtaining BETTER results under certain conditions.

Melanoma molecular subtyping and scoring model construction based on ligand-receptor pairs.

Melanoma is a malignancy of melanocytes, responsible for a high percentage of skin cancer mortality. Ligand-Receptor pairs, a type of cellular communication, are essential for tumor genesis, growth, metastasis, and prognosis. Yet, the role of Ligand-Receptor pairs in melanoma has not been fully elucidated. Our research focused on the function of Ligand-Receptor pairs in melanoma prognosis. We screened 131 melanoma prognosis corresponded ligand-receptor pairs by analyzing the TCGA data of melanoma and the 2293 LR pairs retrieved from the connectomeDB2020 database. And further developed subtypes of melanoma according to the expression of these ligand-receptor pairs by Consensus Clustering. Then we using lasso cox regression and stepwise multivariate regression analysis established a ligand-receptor pairs-based scoring model for the evaluation of melanoma prognosis. Our study demonstrated that the ligand-receptor pairs are vital to the molecular heterogeneity of melanoma, and characterized three different melanoma ligand-receptor pairs subtypes. Among them, the C3 subtype showed a better prognosis, while the C1 subtype exhibited a low prognosis state. And our analysis then found out that this could be related to the differed activation and inhabitation of the cell cycle and immune-related pathways. Using lasso cox regression and stepwise multivariate regression analysis, we further identified 9 key ligand-receptor pairs and established a scoring model that effectively correlated with the prognosis, immune pathways, and therapy of melanoma, showing that the LR.score model was a trustworthy and independent biomarker for melanoma prognosis evaluation. In sum, we found that ligand-receptor pairs are significantly associated with the prognosis and therapy of melanoma. And our ligand-receptor-based scoring model showed potential for the evaluation of melanoma prognosis and immune therapy outcome prediction, which is crucial to the survival for the patients.

Application of septal extension grafts with auricular cartilage in rhinoplasty. / 耳廓软骨鼻中隔延伸支架移植物在鼻整形术中的应用.

OBJECTIVES: Rhinoplasty is one of the most common cosmetic surgeries in China. Septal extension grafts (SEG) have been widely used in rhinoplasty, but there are few reports on SEG derived from ear cartilage. This study aims to explore the effectiveness and stability of auricular cartilage nasal SEG transplantation in Chinese rhinoplasty. METHODS: A retrospective analysis of 35 rhinoplasty patients admitted from September 2019 to March 2022 has been conducted. Among them, 29 patients underwent rhinoplasty for the first time and 6 patients underwent rhinoplasty with the age of 18-32 (average 22.4) years old. The postoperative follow-up was 3-28 (average 18.5) months. The improvement of the nose shape was observed. The changes of the nose tip angle, nasolabial angle, and nasofrontal angle were compared between before and after the operation, and the complications were recorded. RESULTS: All patients who underwent rhinoplasty with a septal extension grafts constructed from the concha cavity and concha cartilage showed significant improvement in nasal contour. The preoperative nasal tip angle, nasolabial angle, and nasofrontal angle were significantly improved compared with 3 months after operation (all P<0.001), and there was no significant difference between 3 months and 14 months after operation (all P>0.05). The appearance of nasal cavity was satisfactory in 32 patients after operation. Columella deviation occurred in 2 patients and 1 patient complained of downward rotation of the nasal tip, which was satisfied after readjustment of the graft. CONCLUSIONS: The simplified SEG derived from auricular cartilage can provide stable support for the nasal tip, the nasal shape is natural after operation, and minimal trauma of unilateral auricle cartilage transplantation remains.

Effectiveness and safety of stem cell therapy for diabetic foot: a meta-analysis update.

BACKGROUND: Diabetic foot (DF) is one of the most common and serious complications of diabetes mellitus (DM), which brings great psychological and economic pressure to patients. This study aimed to evaluate the efficacy of stem cells in the treatment of diabetic foot. METHODS: All relevant studies in Cochrane, Embase, PubMed, Web of Science, China National Knowledge Infrastructure, and WanFang databases were systematically searched for meta-analysis. The outcomes consisted of ulcer or wound healing rate, amputation rate, new vessels, ankle-brachial index (ABI), transcutaneous oxygen pressure (TcPO2), pain-free walking distance, and rest pain score. Dichotomous outcomes were described as risk ratios (RR) with 95% confidence intervals (CIs), while continuous data were presented as standardized mean differences (SMDs) with 95% CIs. Statistical analysis was performed with RevMan 5.3 software. RESULTS: A total of 14 studies with 683 participants were included in the meta-analysis. Meta-analysis showed that stem cell therapy was more effective than conventional therapy in terms of ulcer or wound healing rate [OR = 8.20 (5.33, 12.62)], improvement in lower extremity ischemia(new vessels) [OR = 16.48 (2.88, 94.18)], ABI [MD = 0.13 (0.04, 0.08)], TcO2[MD = 4.23 (1.82, 6.65)], pain-free walking distance [MD = 220.79 (82.10, 359.48)], and rest pain score [MD = - 1.94 (- 2.50, - 1.39)], while the amputation rate was significantly decreased [OR = 0.19 (0.10, 0.36)]. CONCLUSIONS: The meta-analysis of the current studies has shown that stem cells are significantly more effective than traditional methods in the treatment of diabetic foot and can improve the quality of life of patients after treatment. Future studies should conduct large-scale, randomized, double-blind, placebo-controlled, multicenter trials with high-quality long-term follow-up to demonstrate the most effective cell types and therapeutic parameters for the treatment of diabetic foot.

A case of nevoid basal cell carcinoma syndrome dominated by facial basal cell carcinoma. / é¢éƒ¨åŸºåº•ç»†èƒžç™Œä¸ºä¸»çš„ç—£æ ·åŸºåº•ç»†èƒžç™Œç»¼åˆå¾1例.

Nevus-like basal cell carcinoma syndrome (NBCCS) is a rare autosomal dominant disease characterized by the occurrence of multiple maxillofacial keratocysts, basal cell carcinoma, child medulloblastoma, and various skeletal and soft tissue dysplasia. In 2020, a patient with NBCCS dominated by facial basal cell carcinoma was admitted to Xiangya Hospital of Central South University. The patient was an elderly woman. Ten years ago, the systemic mass appeared, especially on the face, but it was not treated. Later, these masses gradually increased in volume and number, and showed invasive properties. The nasal mass was broken and suppurated, seriously affecting the patient's life quality. The patient came to the hospital to improve the symptoms. Staphylococcus aureus and Providencia rettgeri were cultured in the patient's nasal secretions. Nasal sinus enhanced MRI showed that the subcutaneous soft tissue of the right cheek and the anterolateral mucosa of the left nasal cavity were invaded, indicating multiple malignant skin lesions. After admission, local anesthesia was performed and some masses were removed. Pathological examination of the mass showed basal cell carcinoma. After general anesthesia, multiple masses were resected. The postoperative pathological examination showed that multiple basal cell carcinoma invaded the deep dermis near subcutaneous fat layer. Combined with the results of clinical and immunohistochemical examination, the patient was diagnosed as NBCCS. There were no clear tumor thrombus in the vessel and no nerve invasion. No recurrence or new tumor was found after 1 year follow-up. The incidence rate of NBCCS is low and clinical symptoms are different. The patient's life quality is poor and the patient needs long-term individualized treatment.

Hemangioma Endothelial Cells and Hemangioma Stem Cells in Infantile Hemangioma.

BACKGROUND: Hemangioma is one of the most common benign tumors in infants and young children. The 2 most important cells in the course of infantile hemangioma (IH) are hemangioma stem cells (HemSCs) and hemangioma endothelial cells (HemECs). Infantile hemangioma is characterized by massive proliferation of HemECs, but current studies indicate that HemSCs play an important role in pathogenesis of IH. OBJECTIVE: This review aimed to identify molecules that influence HemSC differentiation and HemEC proliferation and apoptosis to help clarify the pathogenesis of IH and provide novel drug targets for the treatment of IH. METHODS: Relevant basic science studies related to IH were identified by searching Google Scholar, Embase, PubMed, MEDLINE, and peer-reviewed journal articles. RESULT: Hemangioma stem cells can differentiate into HemECs, pericytes, and adipocytes. In the proliferating phase of IH, HemSCs mainly differentiate into HemECs and pericytes to promote angiogenesis. In the regressive phase, they mainly differentiate into adipocytes. Therefore, increasing the proportion of HemSCs differentiating into adipocytes, inhibiting the proliferation of HemECs, and promoting the apoptosis of HemECs can facilitate the regression of IH.

Advances in wound repair and regeneration: Systematic comparison of cell free fat extract and platelet rich plasma.

Background: Previous studies showed Cell free fat extract (CEFFE) and Platelet rich plasma (PRP) could effectively accelerate wound healing. However, the comparative study on curative effect is still lacking. A systematic comparison could provide more theoretical support and laboratory basis for the clinical application of CEFFE and PRP. Objective: To compare the efficacy of CEFFE and PRP in promoting skin wound repair. Methods: CEFFE and PRP were prepared according to the literature. The wound repair related factors were measured and compared. In vitro, the effects of both on cell migration, proliferation and tube formation were compared. In vivo, wound healing rate was measured on the 1st, 3rd, 9th, and 12th days after skin injury and treatment. Then the specimens were cut off for histological analysis. Results: Although the total protein content of PRP was significantly around 19 times higher than that of CEFFE, there was no statistical difference in the content of BDNF, EGF and VEGF between CEFFE and PRP. Even the NT-3 content of CEFFE was just slightly higher than that of PRP. The concentration of b-FGF, HGF and TGF-ß and PDGF-BB in PRP is higher than that in CEFFE, but there is only a very small difference between them. In vitro, PRP showed better efficacy than CEFFE in promoting fibroblast proliferation while there was no significant difference in promoting angiogenesis and fibroblast migration. Both PRP and CEFFE could significantly promote wound healing in mice. There was no statistical difference in wound healing between CEFFE and PRP groups in vivo. Immunohistochemical staining of Ki67&CD31 showed that there was no significant difference between PRP and CEFFE groups. Conclusion: The effect of PRP and CEFFE in promoting wound healing was similar. In clinical practice, the acquisition of PRP is relatively more convenient. Containing no cells, CEFFE has the advantage of easier preservation. For patients who have discarded adipose tissue, or contraindications to PRP technology, CEFFE technology may provide a new option for skin wound repair.

A Novel Fat Making Strategy With Adipose-Derived Progenitor Cell-Enriched Fat Improves Fat Graft Survival.

BACKGROUND: A low survival rate is one of the main challenges in fat grafting. OBJECTIVES: This study aimed to evaluate whether microfat obtained by a novel strategy promoted the survival and retention of fat grafts. METHODS: A 5-mm-diameter blunt tip cannula with large side holes (~30 mm2/hole) was used to obtain macrofat. A novel strategy based on a newly invented extracorporeal cutting device was then used to cut the macrofat into microfat, which was named adipose-derived progenitor cell enrichment fat (AER fat); Coleman fat was used as the control. Aliquots (0.5 mL) of both types of fat were transplanted into 10 nude mice and analyzed 10 weeks later. Western blotting, flow cytometry, and immunofluorescence were performed to assess the AER fat characteristics and underlying mechanisms. RESULTS: The retention rate of fat grafts in AER fat-treated animals was significantly higher than that in the Coleman group (mean [standard deviation] 54.6% [13%] vs 34.8% [9%]; P < 0.05) after 10 weeks. AER fat contained more dipeptidyl peptidase-4-expressing progenitor cells (3.3 [0.61] × 103 vs 2.0 [0.46] × 103 cells/mL; P < 0.05), adipose-derived plastic-adherent cells (6.0 [1.10] × 104 vs 2.6 [0.17] × 104 cells/mL; P < 0.001), and viable adipocytes than Coleman fat. Moreover, histologic analysis showed that AER fat grafts had better histologic structure and higher capillary density. CONCLUSIONS: AER fat transplantation is a potential strategy to improve the survival and long-term retention of fat grafts. AER fat contained more dipeptidyl peptidase-4-expressing progenitor cells.

[Nucleosides-based identification model for Fritillariae Cirrhosae Bulbus].

A high performance liquid chromatography( HPLC) method was established for the fast,and precise determination of ten nucleosides in Fritillariae Cirrhosae Bulbus and its counterfeits. Then multivariate statistical analyses,such as clustering analysis,principal component analysis( PCA),and Fisher' s linear discriminant analysis( LDA),were conducted to establish a discriminant function model for an integrated analysis. The results indicated that data acquisition time of a single sample was shortened within 16 min by the HPLC method. In the range of 5-1 000 mg·kg~(-1),the mass concentrations of all nucleosides exhibited good linear relationships with the corresponding peak areas( R2> 0. 999). The spiked recoveries were in the range of 93. 83%-108. 9% with RSDs of0. 12%-1. 3%( n = 5). The limit of quantitation( LOQ) was 0. 98-4. 13 mg·kg~(-1). As revealed by the clustering analysis,Fritillariae Cirrhosae Bulbus and the counterfeits could be discriminated into two clusters based on the content of nucleosides. Fisher's LDA could achieve this discrimination,while PCA dimension reduction failed. The accuracy of the discriminant function model established on the screened characteristic indicators reached 97. 5%. The present study proposed a new identification method of Fritillariae Cirrhosae Bulbus with one-dimensional indicators,which is simple,accurate,and reliable. It can provide a scientific basis for further optimizing the identification techniques for Fritillariae Cirrhosae Bulbus and inspiration for quality control strategy development of Chinese medicinal materials.