Metagenomic analysis reveals altered gut virome and diagnostic potential in pancreatic cancer.

Pancreatic cancer (PC) is a highly aggressive malignancy with a poor prognosis, making early diagnosis crucial for improving patient outcomes. While the gut microbiome, including bacteria and viruses, is believed to be essential in cancer pathogenicity, the potential contribution of the gut virome to PC remains largely unexplored. In this study, we conducted a comparative analysis of the gut viral compositional and functional profiles between PC patients and healthy controls, based on fecal metagenomes from two publicly available data sets comprising a total of 101 patients and 82 healthy controls. Our results revealed a decreasing trend in the gut virome diversity of PC patients with disease severity. We identified significant alterations in the overall viral structure of PC patients, with a meta-analysis revealing 219 viral operational taxonomic units (vOTUs) showing significant differences in relative abundance between patients and healthy controls. Among these, 65 vOTUs were enriched in PC patients, and 154 were reduced. Host prediction revealed that PC-enriched vOTUs preferentially infected bacterial members of Veillonellaceae, Enterobacteriaceae, Fusobacteriaceae, and Streptococcaceae, while PC-reduced vOTUs were more likely to infect Ruminococcaceae, Lachnospiraceae, Clostridiaceae, Oscillospiraceae, and Peptostreptococcaceae. Furthermore, we constructed random forest models based on the PC-associated vOTUs, achieving an optimal average area under the curve (AUC) of up to 0.879 for distinguishing patients from controls. Through additional 10 public cohorts, we demonstrated the reproducibility and high specificity of these viral signatures. Our study suggests that the gut virome may play a role in PC development and could serve as a promising target for PC diagnosis and therapeutic intervention. Future studies should further explore the underlying mechanisms of gut virus-bacteria interactions and validate the diagnostic models in larger and more diverse populations.

Comparison of outcomes and characteristics of patients admitted to the ICU with COVID-19 and other community-acquired pneumonia based on propensity score matching.

OBJECTIVE: To compare the similarities and differences between patients with Coronavirus Disease 2019 (COVID-19) and those with other community-acquired pneumonia (CAP) admitted to the intensive care unit (ICU), utilizing propensity score matching (PSM), regarding hospitalization expenses, treatment options, and prognostic outcomes, aiming to inform the diagnosis and treatment of COVID-19. METHODS: Patients admitted to the ICU of the Third People's Hospital of Datong City, diagnosed with COVID-19 from December 2022 to February 2023, constituted the observation group, while those with other CAP admitted from January to November 2022 formed the control group. Basic information, clinical data at admission, and time from symptom onset to admission were matched using PSM. RESULTS: A total of 70 patients were included in the COVID-19 group and 119 in the CAP group. The patients were matched by the propensity matching method, and 37 patients were included in each of the last two groups. After matching, COVID-19 had a higher failure rate than CAP, but the difference was not statistically significant (73% vs. 51%, p = 0.055). The utilization rate of antiviral drugs (40% vs. 11%, p = 0.003), γ-globulin (19% vs. 0%, p = 0.011) and prone position ventilation (PPV) (27% vs. 0%, p < 0.001) in patients with COVID-19 were higher than those in the CAP, and the differences were statistically significant. The total hospitalization cost of COVID-19 patients was lower than that of CAP patients, and the difference was statistically significant (27889.5 vs. 50175.9, p = 0.007). The hospital stay for COVID-19 patients was shorter than for CAP patients, but the difference was not statistically significant (10.9 vs. 16.6, p = 0.071). CONCLUSION: Our findings suggest that limited medical resources influenced patient outcomes during the COVID-19 pandemic. Addressing substantial demands for ICU capacity and medications during this period could have potentially reduced the mortality rate among COVID-19 patients.

Predicting Bloodstream Infection in High-risk Groups of Liver Failure Patients with Artificial Liver Support System.

Background: Liver failure is a rare, life-threatening disease that has a high mortality rate and affects many organ systems. Bloodstream bacterial infection has played a key role in liver failure patients with plasma exchange-centered artificial liver support systems, but the predicted risk factors of infection have not been fully understood. Objective: We aimed to predict bloodstream bacterial infection in high-risk groups of liver failure patients during a plasma exchange-centered artificial liver support system. Design: This was a prospective cohort study. Setting: This study was performed in Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School. Participants: 118 liver failure patients with plasma exchange-centered artificial liver support system therapy from Nanjing Drum Tower Hospital from November 2019 to November 2020 were selected. Interventions: We used a stepwise binary logistic regression model to select the optimal risk factors of infection with minimum Akaike information criterion, and the Nomogram prognostic model for bloodstream infection was constructed for visualization. Primary Outcome Measures: Risk factors of bloodstream infection (2) predictive accuracy of the constructed nomogram model. Results: Among the 118 liver failure patients, 22 (18.64%) were diagnosed with bloodstream bacterial infection. The univariable and multivariate logistic regression analyses suggested that culture level, glucocorticoids use, number of punctures, blood platelet counts, white blood cell counts, and indwelling catheter time were the sex predictors of bloodstream infection for liver failure patients during plasma exchange-centered artificial liver support system (P = .042, P = .013, P = .025, P = .003, P = .024 and P = .026). The nomogram predictive model was established with high prediction accuracy, of which the area under the curve was 0.935 (95% confidence interval: 0.884-0.986), the sensitivity was 0.955, and the specificity was 0.854. Conclusion: The constructed nomogram prognostic model can recognize the risk factors and accurately predict bloodstream infection for liver failure patients during plasma exchange-centered artificial liver support system.

Effects of Liraglutide on Leptin Promoter Methylation in Ovarian Granulosa Cells of Patients with Polycystic Ovary Syndrome and Obesity.

OBJECTIVE: The aim of the study was to explore the impacts of liraglutide on leptin (LEP) promoter methylation in ovarian granulosa cells of patients with polycystic ovary syndrome and obesity. METHODS: A total of 30 patients with polycystic ovary syndrome and obesity were retrospectively analyzed. According to the method of random grouping, the patients were divided into an observation group and a control group. The control group received metformin, and the observation group received a subcutaneous injection of liraglutide. The therapeutic effects of patients in the two groups were compared. RESULTS: After therapy, the levels of glucose metabolism, lipid metabolism-related indicators, body mass index, LEP, and visfatin of patients were less than those before therapy, and the levels in the observation group were less than the control group (p < 0.05). After therapy, the FSH, E2 and LH levels of patients in the two groups were less than those before therapy, and those in the observation one were less than the control group (p < 0.05). After therapy, the LEP promoter methylation in luteinized granulosa cells in the observation group was less than the control group (p < 0.05). The menstrual cycle establishment ratio, normal ovulation rate, and natural pregnancy ratio of the observation group were greater than the control group (p < 0.05). CONCLUSION: Liraglutide has a therapeutic effect on patients with polycystic ovary syndrome and obesity by reducing the methylation of LEP promoter in luteinized granulosa cells and improving the natural pregnancy rate.

NPTX1 Mediates the Facilitating Effects of Hypoxia-Stimulated Human Adipocytes on Adipose-Derived Stem Cell Activation and Autologous Adipose Graft Survival Rate.

BACKGROUND: Autologous adipose tissue is an ideal material for soft tissue filling and transplantation; however, high volumes of fat absorption over time lead to a relatively low overall survival percentage. The survival and differentiation of adipose-derived stem cells (ADSCs) in the transplanted microenvironment might improve adipose graft survival. Adipocytes have been reported to affect ADSC activation. However, its underlying mechanisms remain unclear. METHODS: Human ADSCs were incubated in a culture medium supplemented with hypoxic or normoxic conditioned culture medium (CM) derived from human adipocytes. Neuronal Pentraxin 1 (NPTX1) was overexpressed or knocked down in human adipocytes using an overexpression vector (NPTX1 OE) or small interfering RNA (siRNA) transfection, respectively. ADSC differentiation and paracrine secretion were assessed. Nude mice were implanted with human adipocytes and ADSCs. The adipose tissue was subsequently evaluated by histological analysis. RESULTS: CM from hypoxic-stimulated human adipocytes significantly facilitated the differentiation ability and paracrine levels of ADSCs. NPTX1 was significantly up-regulated in human adipocytes exposed to hypoxic conditions. In vitro, CM derived from hypoxia-stimulated human adipocytes or NPTX1-overexpressing human adipocytes exposed to normoxia promoted ADSC differentiation and paracrine; after silencing NPTX1, the facilitating effects of hypoxia-treated human adipocytes on ADSC activation were eliminated. Similarly, in vivo, the NPTX1 OE + normoxia-CM group saw improved histological morphology and fat integrity, less fibrosis and inflammation, and increased vessel numbers compared with the OE NC + normoxia-CM group; the adipocyte grafts of the si-NC + hypoxia-CM group yielded the most improved histological morphology, fat integrity, and the most vessel numbers. However, these enhancements of ADSC activation and adipose graft survival were partially abolished by NPTX1 knockdown in human adipocytes. CONCLUSION: NPTX1 might mediate the facilitating effects of hypoxia-stimulated human adipocytes on ADSC activation, thereby improving adipose tissue survival rate after autologous fat transplantation and the effectiveness of autologous fat transplantation through promoting ADSC activation. LEVEL OF EVIDENCE III: 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 .

Implications of Long-Term Double Eyelid Tape Use.

BACKGROUNDS: The widespread adoption of double eyelid tapes (DET) to achieve the desired double eyelid aesthetic has prompted investigations into their long-term effects. Given the delicate and complex anatomy of the eyelid, concerns have emerged about the impact of DETs on eyelid structure and the outcomes of subsequent surgical procedures. METHODS: A cohort of 267 outpatients from our department was recruited between January 2022 and January 2024 to participate in a survey assessing the usage of double eyelid tape (DET). Eyelid laxity was subsequently tested in all outpatients using the Vertical Lid Pull and Parallel Lid Pull methods. Among all participants, 33 underwent double eyelid surgery, with 22 having a history of excessive DET usage and 11 with no DET usage. Post-operative outcomes, including operation duration, satisfaction levels, and complications were recorded. Additionally excised eyelid skin tissues during surgery underwent Masson's staining and EVG staining to analyze collagen and elastic fibers. RESULTS: Among surveyed outpatients (mean age: 23.79 ± 3.71 years, 99.63% female, mean BMI: 21.56 ± 1.75 kg/m2), 56.55% had oculopathy with ametropia being predominant (53.93%). Hooded eyelids were the most prevalent congenital condition (62.54%). Nearly half (49.44%) used Double Eyelid Tapes (DET) for 1-2 years, with 70.04% experiencing discomfort and 70.79% reporting permanent eyelid shape change. Lid pull measurements showed no significant difference in vertical pulls between DET users and non-users, but parallel pulls varied significantly (p<0.05). Complications like asymmetry, numbness, and hypertrophic scars were exclusive to DET users. Physician evaluations favored non-DET users significantly (p<0.05). Histological analysis revealed an interesting finding that individuals using DET have higher collagen levels and notable changes in skin structure when compared to non-users. CONCLUSIONS: Prolonged use of double eyelid tape (DET) may result in eyelid laxity, impacting ocular health and complicating blepharoplasty procedures. 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 .

A New Classification of Pollybeak Deformity and Its Treatment in Asian Rhinoplasty.

BACKGROUND: Supratip deformity, also known as pollybeak deformity, is a common complication of primary and secondary rhinoplasty, characterized by fullness in the supratip region. The correction of pollybeak deformity is a challenging procedure, and its management requires a thorough understanding of the pathogenic mechanism of pollybeak deformity. OBJECTIVES: This study aimed to evaluate the effectiveness of surgical methods for correcting pollybeak deformity in Asian rhinoplasty. METHODS: A retrospective chart review was conducted for 53 patients who underwent pollybeak correction between 2021 and 2022. A modified classification system for pollybeak deformity, the Supratip Fullness Rating Scale (SFRS), was developed to evaluate supratip fullness. The aesthetic outcomes of the patients were assessed by surgeons using the visual analog scale (VAS), and patient was self-assessed using the Rhinoplasty Outcome Evaluation (ROE) scale. RESULTS: The study demonstrated that our surgical method resulted in satisfactory outcomes, with a mean SFRS score change from 2.34[0.65] to 0.23[0.42], a decrease in VAS score from 7.47[1.73] to 1.79[1.67] and a high satisfaction rate of 77.36%, calculated by ROE score. No complications were reported. CONCLUSION: Our surgical method for correcting pollybeak deformity in Asian rhinoplasty can result in satisfactory outcomes, particularly in terms of aesthetic appearance, without any side effects. The use of the modified classification system (SFRS) can provide an objective evaluation of supratip fullness, thereby aiding in the management of this challenging complication. 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 .

Radiographic Study of the Nasal Valve in Different CT Evaluation Method in Asian Patients with Unilateral Cleft Lip Nose.

OBJECTIVE(S): It was the first study to apply and compare two CT methods to assess the validity and clinical significance of structural alterations of the nasal valve in patients with cleft lip nose for assessing nasal ventilation disturbance. METHODS: The study collected data from the NOSE score, as well as internal nasal valve area, internal nasal valve angle, external nasal valve area, and septal deviation angle, to evaluate the differences and correlations between those factors in patients with cleft lip and nose. RESULTS: There were significant differences among INV transverse and coronal area and INV angle on different axial standardized planes between clefted side and non-clefted side. There were statistically significant negative correlations between NOSE scores and those indicators of standard plane and acoustic-axis standardized coronal plane. NOSE score and NSD angle were the indicators of significant differences in the measured data of different complications groups (p = 0.002, p = 0.017). The correlation comparison showed that two standardized CT imaging transverse planes have similar correlations in NOSE score, NSD angle, and complications. CONCLUSION: The results of the two CT evaluation methods showed that there was a significant difference in nasal valve area on the cleft and non-cleft sides, which was significantly associated with nasal ventilation disturbance. The CT evaluation method based on standard axial 3D reconstruction is more convenient to use in the clinic, can be used for pre-surgical evaluation of nasal repair in patients with secondary nasal deformities of unilateral cleft lip, and is valuable for treatment. 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 .

Electroacupuncture may alleviate diabetic neuropathic pain by inhibiting the microglia P2X4R and neuroinflammation.

Diabetic neuropathic pain (DNP) is a common and destructive complication of diabetes mellitus. The discovery of effective therapeutic methods for DNP is vitally imperative because of the lack of effective treatments. Although 2 Hz electroacupuncture (EA) was a successful approach for relieving DNP, the mechanism underlying the effect of EA on DNP is still poorly understood. Here, we established a rat model of DNP that was induced by streptozotocin (STZ) injection. P2X4R was upregulated in the spinal cord after STZ-injection. The upregulation of P2X4R was mainly expressed on activated microglia. Intrathecal injection of a P2X4R antagonist or microglia inhibitor attenuated STZ-induced nociceptive thermal hyperalgesia and reduced the overexpression of brain-derived neurotrophic factor (BDNF), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in the spinal cord. We also assessed the effects of EA treatment on the pain hypersensitivities of DNP rats, and further investigated the possible mechanism underlying the analgesic effect of EA. EA relieved the hyperalgesia of DNP. In terms of mechanism, EA reduced the upregulation of P2X4R on activated microglia and decreased BDNF, IL-1ß and TNF-α in the spinal cord. Mechanistic research of EA's analgesic impact would be beneficial in ensuring its prospective therapeutic effect on DNP as well as in extending EA's applicability.

Different Techniques and Quantitative Measurements in Upper lip lift: A Systematic Review.

BACKGROUND: The upper lip area is an important component of facial aesthetics, and aging produces an increase in the vertical height of the upper lip. Different upper lip lifting techniques are described in the literature. OBJECTIVES: This systematic review aimed to assess both invasive and noninvasive upper lip lifting techniques with patient satisfaction, adverse effects, and quantitative measurements of lifting efficiency. METHODS: This study was conducted per PRISMA guidelines. MEDLINE (via PubMed), EMBASE (OvidSP), and Cochrane Library database were searched from September 14, 2022, to October 12, 2022. Inclusion criteria were reporting on upper lip lift efficiency with quantitative measurements of the lifting degree. RESULTS: Out of 495 studies through the search strategy, nine articles were included in the systematic review, eight for surgical procedures and one for nonsurgical. Surgical procedures seem to have better longevity than nonsurgical techniques. Reported patient satisfaction for both surgical and nonsurgical treatments was good with no severe complaints. The quantitative measures differ between researches and may be classified into two metrics: anatomy ratio computation using photographic analysis or direct height measurement with a caliper and precise parameters utilizing a three-dimensional method. CONCLUSION: In general, surgical therapies seem to have a longer-lasting lifting effect on upper lip lifts with an inevitable scar, while nonsurgical techniques are minimally invasive but temporary. There was a lack of consistency in the measurements used to assess lifting efficiency. A consistent quantitative assessment can be beneficial for both clinical decision-making and high-level evidence research. LEVEL OF EVIDENCE III: 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 .

A Retrospective Study on the Reconstruction of Nasal Septal Mucosal Defects after Asian Rhinoplasty.

BACKGROUND: Nasal septal mucosal defects following rhinoplasty in Asian patients are uncommon complications. However, the reconstruction of such defects presents a challenging task in plastic surgery. The aim of this study was to present comprehensive surgical strategies for the reconstruction of nasal septal mucosal defect after rhinoplasty. METHODS: Thirteen cases presenting with nasal septal mucosal defects between January 2016 and October 2021 were retrospectively reviewed. The size, location, and severity of the defect as well as the extent of cartilage exposure were taken into consideration during evaluation, and surgical approaches were employed for repair accordingly. Patient satisfaction was evaluated using a questionnaire with visual analog scale (VAS) and nasal obstruction symptom evaluation scale (NOSE). RESULTS: The average postoperative follow-up period in this study group was 10.15 months. Reconstruction of nasal septal mucosal defects resulted in successful treatment for all patients. There was no evidence of flap failure or nasal valve stenosis. All patients were satisfied with the reconstruction outcome. CONCLUSIONS: The successful application of surgical techniques for nasal septal mucosal defects after rhinoplasty requires comprehensive consideration. The utilization of the retrograde-flow superior labial artery mucosal flap appears to be a secure, efficient, and effective technique for nasal septal mucosal defect reconstruction in rhinoplasty, particularly in cases with cartilage exposure. 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 .

SAV4 is required for ethylene-induced root hair growth through stabilizing PIN2 auxin transporter in Arabidopsis.

Root hair development is regulated by hormonal and environmental cues, such as ethylene and low phosphate. Auxin efflux carrier PIN2 (PIN-FORMED 2) plays an important role in establishing a proper auxin gradient in root tips, which is required for root hair development. Ethylene promotes root hair development through increasing PIN2 abundance in root tips, which subsequently leads to enhanced expression of auxin reporter genes. However, how PIN2 is regulated remains obscure. Here, we report that Arabidopsis thaliana sav4 (shade avoidance 4) mutant exhibits defects in ethylene-induced root hair development and in establishing a proper auxin gradient in root tips. Ethylene treatment increased SAV4 abundance in root tips. SAV4 and PIN2 co-localize to the shootward plasma membrane (PM) of root tip epidermal cells. SAV4 directly interacts with the PIN2 hydrophilic region (PIN2HL) and regulates PIN2 abundance on the PM. Vacuolar degradation of PIN2 is suppressed by ethylene, which was weakened in sav4 mutant. Furthermore, SAV4 affects the formation of PIN2 clusters and its lateral diffusion on the PM. In summary, we identified SAV4 as a novel regulator of PIN2 that enhances PIN2 membrane clustering and stability through direct protein-protein interactions. Our study revealed a new layer of regulation on PIN2 dynamics.

Annealing temperature effect on the performances of porous ZnO nanosheet-based self-powered UV photodetectors.

Porous ZnO nanosheets (ZnO NSs) may play an important role in self-powered UV photodetectors due to their excellent properties, and their porosity feature affects the photoresponse performance greatly. Porous ZnO NSs were prepared by the hydrothermal method followed with a one-step annealing treatment. The effects of the annealing temperature on the microstructure and photoresponse of porous ZnO NSs and n-ZnO NSs/p-PEDOT:PSS self-powered UV photodetectors were investigated. The results show that the pore density and size of ZnO NSs can be tuned by changing the annealing temperature. At an optimum annealing temperature of 450°C, ZnO NSs exhibit greater absorption capacity for the suitable pore density and size. Meanwhile, more crystal defects due to surface contractile properties increase the number of photogenerated carriers. On this basis, the n-ZnO NSs/p-PEDOT:PSS photodetector presents a larger photocurrent and fast photodetection speed without external bias voltage, indicating the self-powered performance. The higher light absorption and large number of electron-hole pairs resulting from dense pores and surface defects in porous ZnO NSs might account for the enhanced performances.

Generating Daily Soil Moisture at 16 m Spatial Resolution Using a Spatiotemporal Fusion Model and Modified Perpendicular Drought Index.

Soil moisture (SM) is an important parameter in land surface processes and the global water cycle. Remote sensing technologies are widely used to produce global-scale SM products (e.g., European Space Agency's Climate Change Initiative (ESA CCI)). However, the current spatial resolutions of such products are low (e.g., >3 km). In recent years, using auxiliary data to downscale the spatial resolutions of SM products has been a hot research topic in the remote sensing research area. A new method, which spatially downscalesan SM product to generate a daily SM dataset at a 16 m spatial resolution based on a spatiotemporal fusion model (STFM) and modified perpendicular drought index (MPDI), was proposed in this paper. (1) First, a daily surface reflectance dataset with a 16 m spatial resolution was produced based on an STFM. (2) Then, a spatial scale conversion factor (SSCF) dataset was obtained by an MPDI dataset, which was calculated based on the dataset fused in the first step. (3) Third, a downscaled daily SM product with a 16 m spatial resolution was generated by combining the SSCF dataset and the original SM product. Five cities in southern Hebei Province were selected as study areas. Two 16 m GF6 images and nine 500 m MOD09GA images were used as auxiliary data to downscale a timeseries 25 km CCI SM dataset for nine dates from May to June 2019. A total of 151 in situ SM observations collected on 1 May, 21 May, 1 June, and 11 June were used for verification. The results indicated that the downscaled SM data with a 16 m spatial resolution had higher correlation coefficients and lower RMSE values compared with the original CCI SM data. The correlation coefficients between the downscaled SM data and in situ data ranged from 0.45 to 0.67 versus 0.33 to 0.54 for the original CCI SM data; the RMSE values ranged from 0.023 to 0.031 cm3/cm3 versus 0.027 to 0.032 cm3/cm3 for the original CCI SM data. The findings described in this paper can ensure effective farmland management and other practical production applications.

Application of Three-Dimensional Technology in Evaluating the Lower Face Lifting by Regional Platysma Injection with Botulinum Toxin-A.

BACKGROUND: Botulinum toxin-A (BTX-A) injection of regional platysma has been utilized in the lower-part elevation and mandibular contour sculpture. However, the relative research, especially in quantitative assessment appears very spare. Our aim is to investigate the efficacy of three-dimensional (3D) technology as a method for regional platysma injection with BTX-A. MATERIALS AND METHODS: From October 2019 to September 2020, patients with mild or moderate degrees of facial sagging on the lower face were recruited to regional platysma BTX-A injection, and 3D scanning and measurement technology was used to evaluate the difference of curved distances and angels. Patients' improvement was assessed by the global aesthetic improvement scale (GAIS). RESULTS: A total of 57 patients underwent regional platysma BTX-A injection and 32 patients were followed up successfully. Compared with Pre-operative, postoperative facial reference curves distance and cervico-mental angles had statistical differences (p < 0.05). GAIS suggested that the 3D imaging measurement technology could improve satisfaction. CONCLUSION: 3D technology can evaluate the improvement of the lower face with BTX-A. It provides effective measurement methods and raises satisfaction. 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 .

Phytochrome A inhibits shade avoidance responses under strong shade through repressing the brassinosteroid pathway in Arabidopsis.

In dense canopy, a reduction in red to far-red (R/FR) light ratio triggers shade avoidance responses (SARs) in Arabidopsis thaliana, a shade avoiding plant. Two red/far-red (R/FR) light photoreceptors, PHYB and PHYA, were reported to be key negative regulators of the SARs. PHYB represses the SARs under normal light conditions; however, the role of PHYA in the SARs remains elusive. We set up two shade conditions: Shade and strong Shade (s-Shade) with different R/FR ratios (0.7 and 0.1), which allowed us to observe phenotypes dominated by PHYB- and PHYA-mediated pathway, respectively. By comparing the hypocotyl growth under these two conditions with time, we found PHYA was predominantly activated in the s-Shade after prolonged shade treatment. We further showed that under s-Shade, PHYA inhibits hypocotyl elongation partially through repressing the brassinosteroid (BR) pathway. COP1 and PIF4,5 act downstream of PHYA. After prolonged shade treatment, the nuclear localization of COP1 was reduced, while the PIF4 protein level was much lower in the s-Shade than that in Shade. Both changes occurred in a PHYA-dependent manner. We propose that under deep canopy, the R/FR ratio is extremely low, which promotes the nuclear accumulation of PHYA. Activated PHYA reduces COP1 nuclear speckle, which may lead to changes of downstream targets, such as PIF4,5 and HY5. Together, these proteins regulate the BR pathway through modulating BES1/BZR1 and the expression of BR biosynthesis and BR target genes.

Knockdown of TRIM15 inhibits the proliferation, migration and invasion of esophageal squamous cell carcinoma cells through inactivation of the Wnt/ß-catenin signaling pathway.

TRIM15 is a member of tripartite motif-containing protein (TRIM) protein family, which plays important roles in several cancers. The aim of the present study was to evaluate the role of TRIM15 in esophageal squamous cell carcinoma (ESCC). Our results showed that TRIM15 was upregulated in human ESCC tissues and cell lines. In vitro studies showed that knockdown of TRIM15 significantly inhibited the proliferation, migration, and invasion of ESCC cells. Knockdown of TRIM15 caused a significant increase in E-cadherin expression, as well as decreases in expression of N-cadherin and Vimentin proteins. Moreover, in vivo assay proved that tumor growth was suppressed by knockdown of TRIM15. Furthermore, the protein expression levels of ß-catenin, C-myc, and CyclinD1 were markedly decreased in sh-TRIM15-infected ESCC cells. Additionally, treatment with LiCl reversed the inhibitory effects of TRIM15 knockdown on ESCC cells. In conclusion, these findings indicated that knockdown of TRIM15 blocked the growth and metastasis of ESCC in part through inhibiting the Wnt/ß-catenin signaling pathway. Thus, TRIM15 might serve as a promising therapeutic target for ESCC.

Discovery and validation of FBLN1 and ANT3 as potential biomarkers for early detection of cervical cancer.

BACKGROUND: To validate markers for cervical carcinoma (CC) and precancerous lesions related with HPV infections. METHODS: Three different cervical cancer cell lines C-33A, SiHa and Caski were used for secretome profiling by label-free quantitative proteomics. Cervical exfoliated cells and matching serum samples were collected from 284 patients with normal control (n = 75, 26.41 %), precancerous lesions (n = 88, 30.99 %) and early stage cervical squamous carcinoma (n = 121, 42.61 %). HPV subtyping and quantification was performed by PCR and hybridization. 20 candidate proteins identified in previous screening studies (tissue, plasma, cells) were quantified by ELISA. Finally, highly quantitative parallel reaction monitoring mass spectrometry was used to assess the specificities and sensitivities of candidate serum markers. RESULTS: While CC was found to be associated with high-risk HPV subtypes, serum antibodies for high risk HPV were not significantly related to the progression of cervical cancer. Significant differences between patient groups were detected for the four proteins CLU, APOA4, APOE and MLH3, but none would allow clinical application due to insufficient sensitivity and specificity and large variability. Subsequent proteomic secretome analysis of cervical cancer cell lines identified a set of 729 common proteins. Cross referencing this dataset with ELISA measurements revealed six candidate proteins of which two, FBLN1 and ANT3, showed co-occurrence with HPV infection (75.7 % and 85 %, respectively) and had promising diagnostic ability in terms of sensitivity and specificity. After the loss of E6/E7 by using CRISPR/Cas9 gene editing, the content of ANT3 and FBLN1 in KoE6/E7 SiHa were downregulated, which indicated the expression of ANT3 and FBLN1 in cervical cancer may be affected by HPV infection. CONCLUSIONS: FBLN1 and ANT3 might be potential tumor- and HPV-associated serum markers.

Tissue factor-bearing microparticles are a link between acute promyelocytic leukemia cells and coagulation activation: a human subject study.

Acute promyelocytic leukemia (APL) cells constitutively express a large amount of tissue factor (TF) antigen, most of which is present in the cytoplasm. Coagulopathy may persist after induction therapy. We evaluated the overall role of circulating microparticles (MPs) in coagulation activation in APL-associated coagulopathy before and during induction therapy. Eleven adult patients with ≥ World Health Organization's (WHO) grade 2 bleeding events and 11 sex- and age-matched healthy controls were selected. All patients received arsenic trioxide alone as induction therapy. MP-associated TF (MP-TF) activity and MP procoagulant activity (MP-PCA) and 12 coagulation- and anticoagulation-associated indexes were measured before, during, and after induction therapy. Correlation between MP-associated indexes and the other 12 indexes was analyzed in patients. The MP-TF activity was negligible in controls, whereas it markedly increased in patients, dropped rapidly after treatment, and returned to normal at the end of induction therapy. The MP-PCA was similar between patients and controls. The correlation analysis revealed that TF-bearing MPs in patients mainly originated from APL cells. Partially differentiated APL cells could also release TF-bearing MPs, and the higher the degree of APL cell differentiation, the lower the ability of APL cells to release TF-bearing MPs. MP-TF was the main source of active TF in plasma and an important contributor for the coagulation activation in APL-associated coagulopathy. It was MPs released by APL cells/partially differentiated APL cells that served as the vehicle to transfer the large amount of TF to plasma to activate coagulation.

An Efficacy Study of a New Radical Treatment for Acne Vulgaris Using Fat Injection.

BACKGROUND: Fat grafting is a popular operative approach for rejuvenation. Some patients requiring facial fat grafting also have acne. Fat grafting may improve acne in some patients. OBJECTIVES: The aim of this study was to assess whether fat grafting can improve acne and to analyze the mechanism of action by which such improvement occurs. METHODS: Preoperative and postoperative digital photographs were examined retrospectively in 229 patients who underwent fat grafting to compare the numbers of inflammatory acne lesions. In addition, 18 patients with acne who were treated by injection of subdermal stromal vascular fraction gel (SVF-gel) were examined prospectively. The numbers of inflammatory acne lesions before and after treatment were measured, and changes in the levels of CD4+ T-cell infiltration were determined from immunohistochemical staining. RESULTS: Of the 229 retrospectively evaluated patients who underwent fat grafting, 22 had acne and had complete follow-up data; in these patients, the numbers of acne lesions were significantly lower after than before treatment. The 18 patients who received subdermal SVF-gel injection showed evident improvements in inflammatory lesions after more than 1 year of follow-up. CD4+ T-cell infiltration was significantly decreased at week 4. CONCLUSIONS: Facial fat grafting can improve inflammatory acne lesions, perhaps because adipose-derived stem cells, which are plentiful in SVF-gel, reduce CD4+ T-cell-mediated inflammation responses.