Effects of miR126 Expressing Adipose-Derived Stem Cells on Fat Graft Survival and Angiogenesis.

BACKGROUND: Fat transplantation supported by supplementation with ASCs has become a reliable procedure for treating soft tissue defects. However, the unpredictable survival rates for grafted fat remains a challenge with post-transplantation ischemia causing tissue loss. MiR126, which regulates VEGF signaling, is an endothelial cell-specific miRNA known to play an essential role in angiogenesis. We hypothesized that increased miR126 expression in grafted ASCs may promote fat survival within an autologous fat transfer model. METHODS: Rat adipose-derived stem cells were isolated, expanded ex vivo for three passages and then transduced with miR126. We used PCR to verify lentiviral transduction and ELISA to confirm VEGF expression. We then mixed autologous fat tissues from our rat model with transduced ASCs, augmented with a nonsense control or miR126 expression vector. These mixtures were used in the fat grafting procedure, completed via subcutaneous injection at three paravertebral points in each rat. Fat grafts were then harvested on days 4, 7, 14, and 28 post-transplant and evaluated for survival, neovascularization, and protein expression via western blot. RESULTS: VEGF expression levels in ASCs, Con-ASCs, and miR126-ASCs were not significantly different. However, miR126-ASCs experienced significantly improved survival on days 7, 14, and 28 when compared with the other groups. These ASCs also presented with the greatest capillary density on days 7, 14, and 28 post-transplantation as well as increased p-ERK and p-AKT expression when compared to the other groups. CONCLUSION: This data suggests that miR126 augmentation of ASCs may help to enhance the survival and angiogenic capacity of transplanted fat tissues, and that this augmentation was not dependent on VEGF but rather the activation of the ERK/AKT 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 .

Clinical, Pathological Complete Response, and Prognosis Characteristics of HER2-Low Breast Cancer in the Neoadjuvant Chemotherapy Setting: A Retrospective Analysis.

BACKGROUND: The present study was conducted to evaluate the clinical, pathological response, and prognosis characteristics of human epidermal growth factor receptor 2 (HER2)-low breast cancer in the neoadjuvant chemotherapy setting. METHODS: Patients with HER2-negative breast cancer who received neoadjuvant chemotherapy from January 2017 to December 2019 were retrospectively analyzed. HER2-negative breast cancer was divided into two groups: HER2-zero (defined as immunohistochemistry [IHC] 0) and HER2-low (defined as IHC 1+, or IHC 2+ and fluorescence in-situ hybridization-negative. RESULTS: Overall, 314 patients with HER2-negative breast cancer were analyzed. The proportion of HER2-low patients with hormone receptor (HR)-positive disease was higher than in triple-negative breast cancer (TNBC; 75.3% vs. 63.2%, p = 0.032). In HR-positive breast cancer, HER2-low tumors presented less nodal involvement (p = 0.023) and earlier clinical stage (p = 0.015) compared with HER2-zero tumors; however, in TNBC, HER2-low patients had a later clinical stage (p = 0.028). With the pathological complete response (pCR) defined as ypTis/0ypN0, there was no difference in pCR rates among the entire cohort, HR-positive disease, and TNBC. However, with the pCR defined as ypT0ypN0, the pCR rate in HER2-low breast cancer was significantly lower than HER2-zero breast cancer in the entire cohort (24.3% vs. 36.4%, p = 0.032) and the HR-positive subgroup (18.7% vs. 32.1%, p = 0.035), but not for TNBC. Multivariate analysis demonstrated that HER2 status (low vs. zero) was an independent predictive factor for pCR (p = 0.013) in HR-positive breast cancer. There were no statistically significant differences in 3-year disease-free survival and overall survival between HER2-low and HER2-zero breast cancer among the entire cohort, HR-positive disease, and TNBC. CONCLUSIONS: HER2-low breast cancer exhibits specific clinical features and different response to treatment associated with HR status in the neoadjuvant chemotherapy setting.

Protein Subcellular Localization with Gaussian Kernel Discriminant Analysis and Its Kernel Parameter Selection.

Kernel discriminant analysis (KDA) is a dimension reduction and classification algorithm based on nonlinear kernel trick, which can be novelly used to treat high-dimensional and complex biological data before undergoing classification processes such as protein subcellular localization. Kernel parameters make a great impact on the performance of the KDA model. Specifically, for KDA with the popular Gaussian kernel, to select the scale parameter is still a challenging problem. Thus, this paper introduces the KDA method and proposes a new method for Gaussian kernel parameter selection depending on the fact that the differences between reconstruction errors of edge normal samples and those of interior normal samples should be maximized for certain suitable kernel parameters. Experiments with various standard data sets of protein subcellular localization show that the overall accuracy of protein classification prediction with KDA is much higher than that without KDA. Meanwhile, the kernel parameter of KDA has a great impact on the efficiency, and the proposed method can produce an optimum parameter, which makes the new algorithm not only perform as effectively as the traditional ones, but also reduce the computational time and thus improve efficiency.

High-Frequency Ultrasound-Guided Temporal Fat Transplantation: A Safe and Visualized Approach.

SUMMARY: Autologous fat injection is one of the most popular methods for the treatment of temporal depression; however, accurate puncture into the target layer without vascular compromise is hard to achieve. With the aid of high-frequency ultrasonography, the authors performed autologous fat transplantation after visualization in five cases, with satisfactory results. The authors observed the course of superficial temporal vessels, the orbitozygomatic artery, and sentinel veins preoperatively, and used high-frequency ultrasonography to guide lipotransfer into the desired layer intraoperatively, to avoid intravascular injection. With the aid of high-frequency ultrasonography, the authors can easily prevent vascular complications and personalize surgical procedures, as anatomical variations of vasculature can also be detected by means of this method.

A real-world study of anlotinib as third-line or above therapy in patients with her-2 negative metastatic breast cancer.

Background: Antiangiogenic agents provides an optional treatment strategy for patients with metastatic breast cancer. The present study was conducted to evaluate the efficacy and safety of anlotinib as third-line or above therapy for patients with HER-2 negative metastatic breast cancer. Methods: Patients with HER-2 negative metastatic breast cancer who have failed from prior therapy and treated with anlotinib monotherapy or combined with chemotherapy or immunotherapy from June 2018 to December 2020 were retrospectively analyzed based on real-world clinical practice. The primary end point was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Results: 47 patients with HER-2 negative metastatic breast cancer received anlotinib monotherapy or combination therapy as third-line or above therapy. In the general population, 10 patients achieved PR, 25 patients had SD and 12 patients had PD. The overall ORR and DCR were 21.3% and 74.5%, respectively. Subgroup analysis suggested that there were no statistically significant differences in ORR and DCR with respect to HR status (positive vs. negative), treatment programs (monotherapy vs. combination) and treatment type in combination group (chemotherapy vs. immunotherapy). The patients who did not received previously anti-angiogenesis therapy had superior DCR (84.8% vs. 50.0%, P=0.012). Median PFS and OS were 5.0 months (95% CI=4.3-5.7) and 21.0 (95% CI=14.9-27.1) months, respectively. The PFS (6.5m vs. 3.5m, P=0.042)and OS (28.2m vs. 12.6m, P=0.040) were better in HR positive patients than HR negative patients. And simultaneously, patients who received anlotinib combination therapy obtained better PFS (5.5m vs. 3.0m, P=0.045). The incidence of Grade 3-4 adverse events(AEs) was 31.9%. Conclusions: Anlotinib monotherapy or combination therapy provide a viable third-line or above therapeutic strategy in patients with HER-2 negative metastatic breast cancer, a median PFS of 5.0 months was obtained with well tolerated toxicity.

HER2-low expression does not affect the clinical outcomes of metastatic breast cancer treated with CDK4/6 inhibitor: A real-world study.

Background: There is accumulating evidence support human epidermal growth factor receptor 2 (HER2)-low as a biologically distinct subtype of breast cancer. The present study was conducted to explore whether HER2-low expression will affect the clinical efficacy of cyclin-dependent kinase (CDK) 4/6 inhibitor for patients with hormone receptor (HR)-positive, HER-2 negative metastatic breast cancer. Methods: Patients with HR+/HER2- metastatic breast cancer who were treated with palbociclib from January 2019 to June 2021 were retrospectively analyzed based on real-world clinical practice. HER2-zero was defined as immunohistochemistry (IHC) 0, and HER2-low was defined as IHC 1+ or IHC 2+/fluorescence in situ hybridization (FISH) negative. The primary end point was progression free survival (PFS), and the secondary end points were objective response rate (ORR), disease control rate (DCR), overall survival(OS) and safety. Results: 45 patients received palbociclib plus aromatase inhibitor (AI) or fulvestrant therapy, including 24 HER-2-zero and 21 HER-2-low patients. There were no statistically significant differences in clinicopathological characteristics between the two groups. No significant differences were observed in ORR (41.7% vs. 28.6%, P=0.360) and DCR (79.2% vs. 76.2%, P=0.811) between HER-2-zero and HER-2-low patients. And simultaneously, HER2-zero and HER2-low patients obtained similar median PFS (16.2m vs. 14.1m, P=0.263). The median OS was not reached. Neutropenia and leukopenia were the most common adverse events. Grade 3-4 adverse events(AEs) occurred in 58.3% and 57.1% of patients, respectively. Conclusions: HER2-low expression does not affect the clinical efficacy of palbociclib and our present study did not support incorporating HER2-low into systemic therapy decisions for patients with HR+/HER2- metastatic breast cancer treated with CDK4/6 inhibitor.

[Fibrin glue embolization treating intra-operative type I endoleak of endovascular repair of abdominal aortic aneurysm: long-term result].

OBJECTIVES: To analyze the long-term results of fibrin glue embolization to eliminate type I endoleaks after endovascular aneurysm repair (EVAR), and to assess the feasibility and durability of this technique. METHODS: From August 2002 to June 2010, among the 953 EVAR patients, 51 (5.4%) patients underwent intraoperative transcatheter fibrin glue sac embolization to resolve type I endoleak persisting after initial intraoperative maneuvers to close the leak or in necks too short or angulated for cuff placement. Computed tomographic angiography was performed to assess the outcome after 3, 6, and 12 months and annually thereafter. A retrospective study was conducted, and characteristics of the patients, intra-sac pressure, hospital course, and long-term outcomes were recorded. RESULTS: Among the 51 patients, 19 (37.3%) patients had proximal necks long < 10 mm, and 6 (11.8%) patients had proximal neck angulation > 60°; 22 patients (3 additional iliac extension, 14 cuffs, and/or 8 stents) had been placed with additional devices. After fibrin glue injection, 50 (98.0%) of the 51 endoleaks were successfully resolved, and intra-sac pressure (including systolic, diastolic, mean pressures, pulse pressure, and the mean pressure indexes) decreased significantly in these cases. The patient who failed embolotherapy was converted to open surgery (2.0%); he died 2 months later from multiorgan failure. And other two (4.8%) patients died in the peri-operative period from myocardial infarction. The median of follow-up of 48 patients was 45 months (range 4 - 106 months). The mean maximal aneurysm diameter fell from the baseline (61.5 ± 15.2) mm to (48.8 ± 10.1) mm (P = 0.000). Three (6.2%) patients died in the follow-up duration (1 aneurysm-related, died of renal failure which was caused by the compromised renal artery). Cumulative survival was 97.9% at 1 year, 94.5% at 3 years, and 90.8% at 4 years. No recurrent type I endoleak or glue-related complications were observed in follow-up. CONCLUSIONS: Fibrin glue embolization to eliminate type I endoleak after EVAR has yielded promising results in this study, and it can effectively and durable resolve the type I endoleaks. Balloon occlusion of the inflow of the endoleak must be done during glue injection, to enhance the safety and facilitate formation of a structured fibrin clot.

Effect of Subcostal Anterior Quadratus Lumborum Block vs. Oblique Subcostal Transversus Abdominis Plane Block after Laparoscopic Radical Gastrectomy.

OBJECTIVE: To evaluate the analgesic effect of ultrasound-guided subcostal anterior quadratus lumborum block (QLB) for laparoscopic radical gastrectomy surgery. METHODS: Patients (aged 20-65 years, ASA I - II, and weighing 40-75 kg) scheduled for elective laparoscopic radical gastrectomy were enrolled in the current study. Sixty patients were randomly assigned to two groups by computer-generated randomization codes: an ultrasound-guided oblique subcostal transversus abdominis plane block (TAPB) group (group T, n=30) or an ultrasound-guided subcostal anterior QLB group (group Q, n=30). In both groups, bilateral ultrasound-guided oblique subcostal TAPB and subcostal anterior QLB were performed before general anesthesia with 0.25% ropivacaine 0.5 mL/kg. For postoperative management, all patients received patient-controlled intravenous analgesia (PCIA) with nalbuphine and sufentanil after surgery, maintaining visual analogue scale (VAS) scores ≤4 within 48 h. The intraoperative consumption of remifentanil, the requirement for sufentanil as a rescue analgesic, and the VAS scores at rest and coughing were recorded at 1, 6, 12, 24 and 48 h after surgery. The recovery (extubation time after surgery, first ambulation time, first flatus time and length of postoperative hospital stay) and the adverse events (nausea and vomiting, skin pruritus, respiratory depression and nerve-block related complications) were observed and recorded. The primary outcome was the perioperative consumption of opioids. RESULTS: Compared with group T, the intraoperative consumption of remifentanil, requirement for sufentanil and the frequency of PCIA were reduced in group Q. Meanwhile, VAS scores at all points of observation were significantly lower in group Q than in group T. Patients in group Q were also associated with shorter time to first out-of-bed activity and flatus, and shorter length of postoperative hospital stay than group T (P<0.05). There were no skin pruritus, respiratory depression or nerve-block related complications in both groups. CONCLUSION: Compared with ultrasound-guided oblique subcostal TAPB, ultrasound-guided subcostal anterior QLB provided greater opioid-sparing effect, lower visual analogue scores, and shorter postoperative hospital stay for laparoscopic radical gastrectomy.

Treatment of type I endoleak after endovascular repair of infrarenal abdominal aortic aneurysm: success of fibrin glue sac embolization.

PURPOSE: To analyze a single-center experience of fibrin glue sac embolization to eliminate type I endoleaks after endovascular aneurysm repair (EVAR), assessing the feasibility and effectiveness of the technique in long-term follow-up. METHODS: A retrospective study was conducted involving 783 EVAR patients treated between August 2002 and February 2009. Under a standardized protocol, 42 (5.4%) patients (37 men; mean age 73 ± 8 years) underwent intraoperative transcatheter fibrin glue sac embolization to resolve type I endoleak persisting after initial intraoperative maneuvers to close the leak or in necks too short or angulated for cuff placement. Intrasac pressure was measured before and after glue injection. Computed tomographic angiography was performed to assess the outcome after 3, 6, and 12 months and annually thereafter. RESULTS: In this type I endoleak cohort, 16 (38.1%) patients had proximal necks <10 mm long, and 5 (11.9%) patients had proximal neck angulation >60°; 22 additional devices (8 stents, 14 cuffs) had been placed in the initial attempts to resolve the endoleaks. After fibrin glue injection, 41 (97.6%) of the 42 endoleaks were resolved using a mean 15 ± 10 mL of glue. Intrasac pressure decreased significantly in successfully treated cases. The patient who failed embolotherapy was converted to open surgery (2.4%); he died 2 months later from multiorgan failure. Two (4.8%) patients died in the perioperative period from myocardial infarction. One (2.4%) patient developed right lower extremity ischemia unrelated to the fibrin glue treatment. There were no allergic reactions. Over a median follow-up of 39.9 months (range 10-88), 3 (7.1%) patients died (1 aneurysm-related). Cumulative survival was 90.5% at 1 year, 87.0% at 3 years, and 82.6% at 5 years. The mean maximal aneurysm diameter fell from the baseline 59.5 ± 14.7 mm to 49.0 ± 11.6 mm (p<0.001). Of the 4 patients with increased aneurysm diameter during follow-up, 1 was converted, 2 are being observed due to advanced age, and 1 died of renal failure. No recurrent type I endoleak or glue-related complications were observed in follow-up. CONCLUSION: Fibrin glue sac embolization to eliminate type I endoleak after EVAR yielded excellent results in our experience, effectively and durably resolving the leaks. Balloon occlusion of the proximal aorta must be done during glue injection to block proximal flow and facilitate formation of a structured fibrin clot.

Long non-coding RNA CACNA1G-AS1 promotes proliferation and invasion and inhibits apoptosis by regulating expression of miR-205 in human keloid fibroblasts.

BACKGROUND: Keloid is a fibrous tissue proliferative disease in which proliferative scars grow beyond the boundary of the original wound skin. Long non-coding RNAs (lncRNAs), as competing endogenous RNAs (ceRNAs), bind to microRNAs (miRNAs) to regulate various biological processes. The present study was aim to illuminate the mechanism of calcium voltage-gated channel subunit alpha1 G antisense RNA 1 (CACNA1G-AS1) in human keloid fibroblasts. METHODS: CACNA1G-AS1 and miR-205 levels were detected using quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK-8) assay was used to measure the proliferation and transwell assay was performed to evaluate cell invasion. Furthermore, the apoptosis rates of cells were evaluated by flow cytometry analysis, and the activity of caspase-3 in keloid fibroblasts was tested by Caspase-3 activity assay. Dual luciferase reporter assay was carried out to examine the relationship between CACNA1G-AS1 and miR-205 and RNA immunoprecipitation (RIP) assay was conducted to further confirm the relation. RESULTS: CACNA1G-AS1 level was up-regulated in keloid tissues and keloid fibroblasts. CACNA1G-AS1 overexpression promoted proliferation and invasion and suppressed apoptosis of keloid fibroblasts. Moreover, miR-205 was targeted by CACNA1G-AS1 and miR-205 was markedly decreased in keloid tissues and keloid fibroblasts. Also, miR-205 expression was negatively regulated by CACNA1G-AS1 and miR-205 silencing enhanced proliferation and invasion and inhibited apoptosis. Furthermore, CACNA1G-AS1 and miR-205 played the antagonistic role in miR-205 expression, proliferation, invasion, and apoptosis of keloid fibroblasts. CONCLUSION: CACNA1G-AS1 suppressed miR-205 expression to promote proliferation and invasion and inhibit apoptosis in human keloid fibroblasts.

Intralesional injection of bleomycin in the treatment of xanthelasma palpebrarum: A clinical study.

BACKGROUND: Xanthelasma palpebrarum (XP) is the most common type of cutaneous xanthoma and has been treated with intralesional injection of pingyangmycin effectively. However, bleomycin, which has the same effect in antitumor activity as pingyangmycin, has not been applied in the treatment of XP. AIMS: To explore and assess the treatment of xanthelasma by intralesional injection of bleomycin, which has been widely used as an antitumor antibiotic, for the replacement of pingyangmycin. METHODS: Intralesional injection of different concentrations of bleomycin was administered to 44 xanthelasma lesions of 24 patients who have never been treated before, divided into two groups according to age. Photographs were taken and analyzed to assess the therapeutic efficiency. Patients were then followed up for 6-24 months. RESULTS: All the lesions resolved after 1 month of treatment with the intralesional injection of different concentrations of bleomycin. There was no significant difference observed between the two groups. No severe complications had occurred. CONCLUSION: The treatment of XP with intralesional injection of bleomycin is minimally invasive, safe, and effective. Consequently, it also has good cosmetic outcome with no adverse effects.

Synthesis of Carbon Dots with Multiple Color Emission by Controlled Graphitization and Surface Functionalization.

Multiple-color-emissive carbon dots (CDots) have potential applications in various fields such as bioimaging, light-emitting devices, and photocatalysis. The majority of the current CDots to date exhibit excitation-wavelength-dependent emissions with their maximum emission limited at the blue-light region. Here, a synthesis of multiple-color-emission CDots by controlled graphitization and surface function is reported. The CDots are synthesized through controlled thermal pyrolysis of citric acid and urea. By regulating the thermal-pyrolysis temperature and ratio of reactants, the maximum emission of the resulting CDots gradually shifts from blue to red light, covering the entire light spectrum. Specifically, the emission position of the CDots can be tuned from 430 to 630 nm through controlling the extent of graphitization and the amount of surface functional groups, COOH. The relative photoluminescence quantum yields of the CDots with blue, green, and red emission reach up to 52.6%, 35.1%, and 12.9%, respectively. Furthermore, it is demonstrated that the CDots can be uniformly dispersed into epoxy resins and be fabricated as transparent CDots/epoxy composites for multiple-color- and white-light-emitting devices. This research opens a door for developing low-cost CDots as alternative phosphors for light-emitting devices.

Applied Anatomy of the Femoral Veins in Macaca fascicularis / Anatomía Aplicada de las Venas Femorales en Macaca fascicularis

The aim was to understand the anatomical features of the venous valve in Macaca fascicularis and to compare it with that of humans. The bilateral lower limbs (24 limbs from 12 animals) of Macaca fascicularis cadavers were dissected, and the femoral veins (FVs) were equally divided into distal, intermediate, and proximal sections. The external diameter of the FV in each section was measured. The venous valves were observed microscopically and stained with hematoxylin and eosin as well as trichrome. Data describing the human venous valve were collected from the current literature. No great saphenous veins were found among the 24 lower limbs from the Macaca fascicularis cadavers. The external diameters of the FVs in the distal, intermediate, and proximal sections were 3.53 ± 0.37 mm, 3.42 ± 0.55 mm, and 3.37 ± 0.54 mm, respectively. In most cases, there was one venous bivalve located in the FV approximately 0-2.71 mm below the junction of the FV and the deep femoral vein. Endothelium covered the luminal and sinusal surfaces of the leaflets. Abundant collagen fibers were found under the endothelial cells beneath the luminal surface of the leaflets. An elastin fiber network was located under the sinus endothelial surface. Smooth muscle cells in the FV extend to the edge of the valve. The venous valve of Macaca fascicularis is similar to that of humans, both morphologically and histologically. However, there is only one venous bivalve and no great saphenous vein in Macaca fascicularis.

El objetivo fue comprender las características anatómicas de la válvula venosa en Macaca fascicularis y compararla con la de los humanos. Fueron disecados bilateralmente los miembros pélvicos (24 miembros de 12 animales) de cadáveres de Macaca fascicularis; las venas femorales (VF) fueron divididas en secciones distal, media y proximal. Se midió el diámetro externo de las VFs en cada sección. Las válvulas venosas se observaron microscópicamente y se tiñeron con H-E y tricrómico. Los datos para describir la válvula venosa humana se obtuvieron desde la literatura. No se encontraron venas safenas magnas entre los 24 miembros inferiores. Los diámetros externos de las VFs en las secciones distal, media y proximal fueron 3,53±0,37 mm, 3,42 mm±0,55, y 3,37±0,54 mm, respectivamente. En la mayoría de los casos, hubo vena bivalva situada aproximadamente 0-2,71 mm debajo de la unión de la VF y la vena femoral profunda. El endotelio cubrió las superficies luminal y sinusal. Se observaron abundantes fibras de colágeno en las células endoteliales bajo la superficie luminal de las válvulas. Una red de fibras de elastina se encontró bajo la superficie del seno endotelial. Las células musculares lisas en las VFs se extiendían hasta el margen de la válvula. La válvula venosa del Macaca fascicularis es similar a la de los seres humanos, morfológica e histológicamente. Sin embargo, sólo hubo una vena bivalvular, y no se observaron venas safenas en Macaca fascicularis.