Peceleganan Spray for the Treatment of Skin Wound Infections: A Randomized Clinical Trial.

Importance: Peceleganan spray is a novel topical antimicrobial agent targeted for the treatment of skin wound infections. However, its efficacy and safety remain unclear. Objective: To assess the safety and efficacy of peceleganan spray for the treatment of wound infections. Design, Setting, and Participants: This multicenter, open-label, phase 3 randomized clinical trial recruited and followed up 570 adult patients diagnosed with secondary open wound infections from 37 hospitals in China from August 23, 2021, to July 16, 2022. Interventions: Patients were randomized to 2 groups with a 2:1 allocation. One group received treatment with 2% peceleganan spray (n = 381) and the other with 1% silver sulfadiazine (SSD) cream (n = 189). Main Outcomes and Measures: The primary efficacy outcome was the clinical efficacy rate (the number of patients fulfilling the criteria for efficacy of the number of patients receiving the treatment) on the first day following the end of treatment (day 8). The secondary outcomes included the clinical efficacy rate on day 5 and the bacterial clearance rate (cases achieving negative bacteria cultures after treatment of all cases with positive bacteria cultures before treatment) on days 5 and 8. The safety outcomes included patients' vital signs, physical examination results, electrocardiographic findings, blood test results, and adverse reactions. Results: Among the 570 patients randomized to 1 of the 2 groups, 375 (98.4%) in the 2% peceleganan treatment group and 183 (96.8%) in the 1% SSD control group completed the trial (n = 558). Of these, 361 (64.7%) were men, and the mean (SD) age was 48.6 (15.3) years. The demographic characteristics were similar between groups. On day 8, clinical efficacy was achieved by 339 patients (90.4%) in the treatment group and 144 (78.7%) in the control group (P < .001). On day 5, clinical efficacy was achieved by 222 patients (59.2%) in the treatment group and 90 (49.2%) in the control group (P = .03). On day 8, bacterial clearance was achieved by 80 of 334 patients (24.0%) in the treatment group and in 75 of 163 (46.0%) in the control group (P < .001). On day 5, bacterial clearance was achieved by 55 of 334 patients (16.5%) in the treatment group and 50 of 163 (30.7%) in the control group (P < .001). The adverse events related to the application of peceleganan spray and SSD cream were similar. Conclusions and Relevance: This randomized clinical trial found that peceleganan spray is a safe topical antimicrobial agent with a satisfactory clinical efficacy rate for the treatment of skin wound infections, while the effectiveness of bacterial clearance remains uncertain. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2100047202.

Transcriptomics reveals age-related changes in ion transport-related factors in yak lungs.

Yaks inhabit high-altitude, low-oxygen regions, where ion transport functions play a crucial role in maintaining intracellular and extracellular ionic balance and regulating pulmonary vascular tension. These functions affect pulmonary ventilation and blood flow rate, aiding tissue development and enhancing oxygen transfer efficiency, thus facilitating better adaptation to hypoxic environments. To investigate the regulatory mechanisms of ion transport-related factors on the growth and development of yak lungs, we employed RNA sequencing (RNA-seq)for sequencing the transcriptome in the lung tissues of neonatal (1-day-old), juvenile (1-year-old), and adult (4-year-old) yaks. We also performed differential gene expression and functional analyses. The results yielded 26 genes associated with ion transport, mainly enriched in the salivary and pancreatic secretion pathways. Finally, we used several methods including quantitative polymerase chain reaction (qRT-PCR), and Western blotting (WB), immunohistochemical (IHC) and immunofluorescence (IF) staining to determine the distribution of the expression of the ion transport genes FOXI1, KCNMA1, and SLC12A2 in yak lung tissues. qRT-PCR and WB results indicated that mRNA and protein relative expression levels of FOXI1 and SLC12A2 were significantly higher in neonatal yaks than in juvenile and adult yaks (all p < 0.05), whereas those of KCNMA1 were significantly higher in adult yaks than in neonatal and juvenile yaks (all p < 0.05). IHC and IF results demonstrated that FOXI1, KCNMA1, and SLC12A2 were distributed among the epithelial mucosal layers (including ciliated, goblet, and Clara cells) of the yaks' bronchi and their branches in the lungs across different age groups of yak. Therefore, our results suggested that FOXI1, KCNMA1, and SLC12A2 may be strongly associated with the development and aging processes in yak lungs. These results provide insights into the molecular mechanisms underlying the yak's adaptation to high-altitude environments and valuable references for further research.

Exploring the role of psychological assistance hotlines in improving mental health problems among Chinese adult women: A perspective based on social expectations and gender roles.

This paper looks at how social expectations and gender roles affect the mental health of Chinese women. Traditional Chinese culture, influenced by Confucianism and patriarchy, still has a negative impact on women's mental well-being, despite efforts for gender equality. Women's mental health is vital for both individuals and society, and this study aims to understand these issues better to help shape policies and interventions.

Comparable Effects on Healing between Autologous Diabetic Adipose-Derived Stem Cells and Allogeneic Normal Counterparts.

BACKGROUND: Adipose-derived stem cell (ASC) therapy is considered a promising strategy for improving impaired wound healing, especially in diabetics. Although the therapeutic potential of allogeneic ASCs from healthy donors is naturally limited, that of autologous ASCs from diabetic patients is questionable. The aim of this study was to investigate the impact of diabetic ASCs in the treatment of diabetic wounds. METHODS: Diabetic ASCs (DMA) and nondiabetic ASCs were isolated from db/db and C57BL/6J mice, and characterized by immunocytochemistry, proliferation, differentiation, and gene expression assays. The effects of both ASCs on healing were investigated using 36 male 10- to 12-week-old db/db mice. Wound size was measured semiweekly until day 28, and histologic and molecular analyses were performed at day 14. RESULTS: Both ASCs had fibroblast-like morphology and were CD44 + /CD90 + /CD34 - /CD45 - at passage 4. Compared with nondiabetic ASCs in vitro, DMA proliferative capability was restored by passage 4 ( P > 0.05). Although DMA osteogenesis was attenuated ( P < 0.01), both ASCs had similar adipogenesis and expressions of PPARγ/LPL/OCN/RUNX2 ( P > 0.05). In vivo experiments showed that, compared with phosphate-buffered saline control, both ASCs are comparable in improving wound healing ( P < 0.0001), angiogenesis ( P < 0.05), epithelial cell proliferation ( P < 0.05), and granulation tissue formation ( P < 0.0001). CONCLUSIONS: In both in vitro and in vivo murine models, DMAs have shown a comparable therapeutic capacity to normal ASCs in promoting diabetic wound healing by improving angiogenesis, reepithelialization, and granulation tissue formation. These results support clinical applications of autologous ASCs in diabetic wound treatments. CLINICAL RELEVANCE STATEMENT: This work has particular surgical relevance as it highlights a theoretical and clinical pathway to use diabetic patients' own ASCs to treat their wounds, bypassing any concerns of cross-host sourcing issues in regenerative medicine.

Balance of Gata3 and Ramp2 in hepatocytes regulates hepatic vascular reconstitution in postoperative liver regeneration.

BACKGROUND & AIMS: Post-hepatectomy liver failure (PHLF) leads to poor prognosis in patients undergoing hepatectomy, with hepatic vascular reconstitution playing a critical role. However, the regulators of hepatic vascular reconstitution remain unclear. In this study, we aimed to investigate the regulatory mechanisms of hepatic vascular reconstitution and identify biomarkers predicting PHLF in patients undergoing hepatectomy. METHODS: Candidate genes that were associated with hepatic vascular reconstitution were screened using adeno-associated virus vectors in Alb-Cre-CRISPR/Cas9 mice subjected to partial hepatectomy. The biological activities of candidate genes were estimated using endothelial precursor transfusion and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) models. The level of candidates was detected in biopsies from patients undergoing ALPPS. Risk factors for PHLF were also screened using retrospective data. RESULTS: Downregulation of Gata3 and upregulation of Ramp2 in hepatocytes promoted the proliferation of liver sinusoidal endothelial cells and hepatic revascularization. Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor A (VEGFA) played opposite roles in regulating the migration of endothelial precursors from bone marrow and the formation of new sinusoids after hepatectomy. Gata3 restricted endothelial cell function in patient-derived hepatic organoids, which was abrogated by a Gata3 inhibitor. Moreover, overexpression of Gata3 led to higher mortality in ALPPS mice, which was improved by a PEDF-neutralizing antibody. The expression of Gata3/RAMP and PEDF/VEGFA tended to have a negative correlation in patients undergoing ALPPS. A nomogram incorporating multiple factors, such as serum PEDF/VEGF index, was constructed and could efficiently predict the risk of PHLF. CONCLUSIONS: The balance of Gata3 and Ramp2 in hepatocytes regulates the proliferation of liver sinusoidal endothelial cells and hepatic revascularization via changes in the expression of PEDF and VEGFA, revealing potential targets for the prevention and treatment of PHLF. IMPACT AND IMPLICATIONS: In this study, we show that the balance of Gata3 and Ramp2 in hepatocytes regulates hepatic vascular reconstitution by promoting a shift from pigment epithelium-derived factor (PEDF) to vascular endothelial growth factor A (VEGFA) expression during hepatectomy- or ALLPS (associating liver partition and portal vein ligation for staged hepatectomy)-induced liver regeneration. We also identified serum PEDF/VEGFA index as a potential predictor of post-hepatectomy liver failure in patients who underwent hepatectomy. This study improves our understanding of how hepatocytes contribute to liver regeneration and provides new targets for the prevention and treatment of post-hepatectomy liver failure.

Exploring the causal relationship between inflammatory cytokines and inflammatory arthritis: A Mendelian randomization study.

OBJECTIVES: Previous studies have reported an association between inflammatory cytokines and inflammatory arthritis, including Ankylosing spondylitis (AS), rheumatoid arthritis (RA), and psoriatic arthritis (PsA). This study aims to explore the causal relationship between inflammatory cytokines and AS, RA, and PsA using Mendelian randomization (MR). METHODS: We conducted a bidirectional two-sample MR analysis using genetic summary data from a publicly available genome-wide association study (GWAS) that included 41 genetic variations of inflammatory cytokines, as well as genetic variant data for AS, RA, and PsA from the FinnGen consortium. The main analysis method used was Inverse variance weighted (IVW) to investigate the causal relationship between exposure and outcome. Additionally, other methods such as MR Egger, weighted median (WM), simple mode, and weighted mode were employed to strengthen the final results. Sensitivity analysis was also performed to ensure the reliability of the findings. RESULTS: The results showed that macrophage colony-stimulating factor (MCSF) was associated with an increased risk of AS (OR = 1.163, 95 % CI = 1.016-1.33, p = 0.028). Conversely, high levels of TRAIL and beta nerve growth factor (ß-NGF) were associated with a decreased risk of AS (OR = 0.892, 95 % CI = 0.81-0.982, p = 0.002; OR = 0.829, 95 % CI = 0.696-0.988, p = 0.036). Four inflammatory cytokines were found to be associated with an increased risk of PsA: vascular endothelial growth factor (VEGF) (OR = 1.161, 95 % CI = 1.057-1.275, p = 0.002); Interleukin 12p70 (IL12p70) (OR = 1.189, 95 % CI = 1.049-1.346, p = 0.007); IL10 (OR = 1.216, 95 % CI = 1.024-1.444, p = 0.026); IL13 (OR = 1.159, 95 % CI = 1.05-1.28, p = 0.004). Interleukin 1 receptor antagonist (IL-1rα) was associated with an increased risk of seropositive RA (OR = 1.181, 95 % CI = 1.044-1.336, p = 0.008). Similarly, genetic susceptibility to inflammatory arthritis was found to be causally associated with multiple inflammatory cytokines. Lastly, the sensitivity analysis supported the robustness of these findings. CONCLUSIONS: This study provides additional insights into the relationship between inflammatory cytokines and inflammatory arthritis, and may offer new clues for the etiology, diagnosis, and treatment of inflammatory arthritis.

Adult female callers' characteristics and mental health status: a retrospective study based on the psychological assistance hotline in Hangzhou.

OBJECTIVE: This study aims to analyze the basic characteristics and mental health status of adult female callers to the psychological assistance helpline in Hangzhou City, in order to provide targeted services for effectively intervening in the psychological crises of this group. METHODS: Data from adult female callers to a helpline in Hangzhou City were collected between 2019 and 2022, encompassing demographic information and discussed issues. The data were analyzed according to age groups, marital status, and call times. The mental health status of the adult female population was measured by two indicators-mood status and suicide risk. RESULTS: The study included 15,580 adult female callers. Among them, 52.2% were aged 30 and below, 62.1% were unmarried, and 42.6% were from other provinces. The primary types of calls were related to mental health (56.5%), romantic relationships (11%), and marriage/family issues (13%). Adults aged 30 and below had more consultations about romantic relationships, work, and study-related issues compared to those over 30. Those over 30 sought more advice on marriage/family and child education. Younger callers displayed higher levels of depression and suicide risk compared to older callers. Unmarried callers had a higher proportion of moderate depression and suicide risk than married callers. Higher education levels were associated with lower depression levels (OR = 0.631,95%CI:0.439-0.906, P = 0.013) and high-risk proportions (OR = 0.328,95%CI:0.147-0.733, P = 0.007). Late evening callers had a higher high-risk proportion (OR = 5.326,95%CI:2.633-10.775, P < 0.001), and employed individuals had lower high-risk proportions compared to unemployed callers (OR = 0.536,95%CI:0.320-0.897, P = 0.018). CONCLUSION: The mental health status of female callers aged 30 and below, unemployed individuals, and those calling in the latter part of the night have relatively poorer mental health and are more likely to be at risk for suicide, which needs to be taken seriously, and more professional and targeted intervention services need to be enhanced in the hotline.

How environmental leadership shapes green innovation performance: A resource-based view.

Considering rapid climate change and its effects, an increasing number of enterprises are paying more attention to environmental protection behavior in order to realize their green innovation activities. However, environmental leadership is critical for delivering green innovation in business and industry. As such, can environmental leadership promote the green innovation performance of enterprises? If so, what is the influence mechanism? In the previous research on environmental leadership, the impact of environmental leadership on the green innovation performance of enterprises had not yet been effectively explored. Therefore, drawing on a resource-based view, this study explored the mechanism through which environmental leadership influences a firm's green innovation performance. In this study, with the help of the mature scale at home and abroad, variables were measured, and the relationship between variables was verified by multiple regression analysis using samples collected from 224 heavy-polluting enterprises in western China at multiple time points. It was found that (1) environmental leadership has significant positive effects on green product innovation performance and green process innovation performance; (2) proactive environmental strategies partly mediate the relationships between environmental leadership and green product, as well as green process innovation performance; and (3) a firm's organizational structure positively moderates the relationship between environmental leadership and proactive environmental strategies. Therefore, the results of our study provide theoretical and practical contributions for research on environmental leadership and proactive environmental strategies.

Federated Visualization: A Privacy-Preserving Strategy for Aggregated Visual Query.

We present a novel privacy preservation strategy for aggregated visual query of decentralized data. The key idea is to imitate the flowchart of the federated learning framework, and reformulate the visualization process within a federated infrastructure. The federation of visualization is fulfilled by leveraging a shared global module that composes the encrypted externalizations of transformed visual features of data pieces in local modules. We design two implementations of federated visualization: a prediction-based scheme, and a query-based scheme. We demonstrate the effectiveness of our approach with a set of visual forms, and verify its robustness with evaluations. We report the value of federated visualization in real scenarios with an expert review.

Visual Diagnostics of Parallel Performance in Training Large-Scale DNN Models.

Diagnosing the cluster-based performance of large-scale deep neural network (DNN) models during training is essential for improving training efficiency and reducing resource consumption. However, it remains challenging due to the incomprehensibility of the parallelization strategy and the sheer volume of complex data generated in the training processes. Prior works visually analyze performance profiles and timeline traces to identify anomalies from the perspective of individual devices in the cluster, which is not amenable for studying the root cause of anomalies. In this paper, we present a visual analytics approach that empowers analysts to visually explore the parallel training process of a DNN model and interactively diagnose the root cause of a performance issue. A set of design requirements is gathered through discussions with domain experts. We propose an enhanced execution flow of model operators for illustrating parallelization strategies within the computational graph layout. We design and implement an enhanced Marey's graph representation, which introduces the concept of time-span and a banded visual metaphor to convey training dynamics and help experts identify inefficient training processes. We also propose a visual aggregation technique to improve visualization efficiency. We evaluate our approach using case studies, a user study and expert interviews on two large-scale models run in a cluster, namely, the PanGu- α 13B model (40 layers), and the Resnet model (50 layers).

Distribution and Expression of Pulmonary Ionocyte-Related Factors CFTR, ATP6V0D2, and ATP6V1C2 in the Lungs of Yaks at Different Ages.

In order to reveal the distribution and expression characteristics of the pulmonary ionocyte-related factors CFTR, ATP6V0D2, and ATP6V1C2 in the lungs of yaks of different ages. Explore the possible regulation of these pulmonary ionocyte-related factors in the yak lung for adaptation to high-altitude hypoxia. The localization and expression of CTFR, ATP6V0D2, and ATP6V1C2 in the lungs of newborn, juvenile, adult, and elderly yaks were studied using immunohistochemistry, quantitative reverse transcription PCR, and Western blotting. Immunohistochemistry showed that CFTR, ATP6V0D2 and ATP6V1C2 were mainly localized in the ciliated cells and club cells of the epithelial mucosal layer of the bronchus and its branches in the lungs. For the qRT-PCR, expression of CFTR, ATP6V0D2 and ATP6V1C2 in the yak lungs varied according to age. For Western blotting, CFTR expression in the newborn group was significantly higher than in the other three groups. ATP6V0D2 expression of the adult group was significantly higher. ATP6V1C2 expression was the highest in the juvenile group (p < 0.05). This study showed that ciliated cells and club cells were related to the pulmonary ionocytes in yaks. CFTR, ATP6V0D2, and ATP6V1C2 were related to adaptations of yak lungs to high altitude hypoxia, through prevention of airway damage.

Pressure does not affect fibrotic function of dermal fibroblast through an in vitro 3D hydrogel culture model.

Pressure therapy has been used for the prevention and treatment of hypertrophic scars for decades. However, the cellular and molecular mechanisms of this treatment modality have not been fully elaborated, leading to long-lasting controversies regarding its clinical effectiveness. In this current study, we adopted an in vitro 3D culture and compression model to explore the effect of pressure force on fibroblasts, in order to further explain the working mechanism of compression force during pressure treatment. Human dermal fibroblasts were cultured in the 3D culture hydrogel and treated with 1.5 atm of external compression force through a syringe tube device, for 4, 8, and 20 h respectively. RNA-seq identified 437 differentially regulated genes after an 8-h compression intervention compared with control cells, among which 256 genes were up-regulated and 181 genes were down-regulated. Further q-PCR analysis confirmed that early growth response 1(EGR1) and c-fos were down-regulated after an 8-h compression intervention. However, the down-regulation of EGR1 and c-fos at the mRNA level does not lead to altered protein synthesis through western blot, for both 8 and 20-h time points after pressure intervention. Genes closely related to the fibrotic function of fibroblasts including type I collagen (COL1), type III collagen (COL3), transforming growth factor ß1(TGF-ß1), matrix metallopeptidase 1 (MMP1), matrix metallopeptidase 1 (TIMP1), connective tissue growth factor (CTGF), α smooth muscle actin (α-SMA), and fibronectin 1 (FN1), were also unaffected after pressure treatment for 8 h. The current study indicated that in our 3D hydrogel culture model, pressure does not directly affect the fibrotic function of dermal fibroblast in vitro. Indirect regulation including reducing oedema, blood perfusion, and tension could be a more possible mechanism of pressure therapy.

To close or open the tank input water valve: Secondary water-supply systems with double tanks will induce a higher microbial risk.

Secondary water supply systems (SWSSs) are widely used to supply water to high-rise households in urban residential buildings. A special mode of double tanks with one used while another was spared was noted in SWSSs, which would facilitate microbial growth due to longer water stagnation in the spare tank. There are limited studies on the microbial risk of water samples in such SWSSs. In this study, the input water valves of the operational SWSSs consisting of double tanks were artificially closed and opened on time. Propidium monoazide-qPCR and high-throughput sequencing were performed to systematically investigate the microbial risks in water samples. After closing the tank input water valve, it may take several weeks to replace the bulk water in the spare tank. The residual chlorine concentration in the spare tank decreased by up to 85 % within 2-3 days compared with that in the input water. The microbial communities in the spare and used tank water samples clustered separately. High bacterial 16S rRNA gene abundance and pathogens-like sequences were detected in the spare tanks. Most antibiotic-resistant genes (11/15) in the spare tanks showed an increase in their relative abundance. Moreover, when both tanks within one SWSS were in use, the water quality of the used tank water samples deteriorated to varying degrees. Overall, running SWSSs with double tanks will reduce the replacement rate of water in one storage tank, and consumers who use taps served by the presented SWSSs may have a higher microbial risk.

Efficacy and Safety of PL-5 (Peceleganan) Spray for Wound Infections: A Phase IIb Randomized Clinical Trial.

OBJECTIVE: To assess the safety and efficacy of antimicrobial peptide PL-5 (Peceleganan) spray in the treatment of wound infections. BACKGROUND: Antimicrobial peptide PL-5 spray is a novel topical antimicrobial agent. METHODS: We conducted a multicenter, open-label, randomized, controlled phase IIb clinical trial to evaluate the efficacy and safety of PL-5 spray, as compared with silver sulfadiazine, in patients with skin wound infections. The primary efficacy outcome was the clinical efficacy rate on the first day after ending the treatment (D8). The secondary efficacy outcome was the clinical efficacy rate on the fifth day posttreatment (D5), the bacteria clearance rate, and the overall efficacy rate at the mentioned 2 time points. The safety outcomes included adverse reactions and pharmacokinetic analysis posttreatment. RESULTS: A total of 220 patients from 27 hospitals in China were randomly assigned to 4 groups. On D8, the efficacy rate was 100.0%, 96.7%, 96.7% for the 1‰ PL-5, 2‰ PL-5, 4‰ PL-5 groups, respectively, as compared with 87.5% for the control group. The efficacy rate among the 4 groups was significantly different ( P <0.05). On D5, the efficacy rate was 100.0%, 93.4%, 98.3% for the 1‰ PL-5, 2‰ PL-5, 4‰ PL-5 groups, respectively, as compared with 82.5% for the control group. The efficacy rate among the 4 groups was significantly different ( P <0.05). The blood concentration of PL-5 was not detectable in pharmacokinetic analysis. No severe adverse event related to the application of PL-5 was reported. CONCLUSIONS: Antimicrobial peptide PL-5 spray is safe and effective for the treatment of skin wound infections. TRIAL REGISTRATION: ChiCTR2000033334.

A Predictive Clinical-Radiomics Nomogram for Differentiating Tuberculous Spondylitis from Pyogenic Spondylitis Using CT and Clinical Risk Factors.

Objective: The study aimed to develop and validate a nomogram model with clinical risk factors and radiomic features for differentiating tuberculous spondylitis (TS) from pyogenic spondylitis (PS). Methods: A total of 254 patients with TS (n = 141) or PS (n = 113) were randomly divided into training (n = 180) and validation (n = 74) groups. In addition, 43 patients (TS = 22 and PS = 21) were collected to construct a test cohort. t-test analysis, de-redundancy analysis, and minimum absolute shrinkage and selection operator (lasso) algorithm were utilized on the training set to obtain the optimal radiomics features from computed tomography (CT) for constructing the radiomics model and determine the radiomics score (Rad-score). Eight clinical risk predictors were identified to develop the clinical model. Combined with clinical risk predictors and Rad-scores, a nomogram model was constructed using multivariate logistic regression analysis. Results: A total of 1781 features were extracted, and 12 optimal radiomic features were utilized to construct the radiomic model and determine the Rad-score. The combined clinical radiomics model revealed good discrimination performance in both the training cohort and the validation cohort (AUC = 0.891 and 0.830) and was superior to the clinical (AUC = 0.807 and 0.785) and radiomics (AUC = 0.796 and 0.811) models. The calibration curve and DCA also depicted that the nomogram had better clinical efficacy. The discriminative performance of the model is well validated in the test cohort (AUC=0.877). Conclusion: The clinical radiomic nomogram could serve as a promising predictive tool for differentiating TS from PS, which could be helpful for clinical decision-making.

In situ scarless skin healing of a severe human burn wound induced by a hCTLA4Ig gene-transferred porcine skin graft.

Preventing fibrosis or hypertrophic scar formation following tissue damage is still a big challenge despite the numerous approaches clinicians currently use. Hitherto, no written account was available of a successful case of scarless skin healing after a severe burn injury. Here, we report the first case of the "perfect regenerative healing" of a severe burn wound with no hypertrophic scar formation in which a postage stamp skin autograft was covered with human cytotoxic-T-lymphocyte associated antigen4-immunoglobulin (hCTLA4Ig) gene-transferred pig skin. We also discuss the mechanisms involved in the scarless healing of human burn wounds.

Hepatocyte-derived VEGFA accelerates the progression of non-alcoholic fatty liver disease to hepatocellular carcinoma via activating hepatic stellate cells.

Non-alcoholic fatty liver disease (NAFLD) is emerging as an epidemic risk factor for hepatocellular carcinoma (HCC). The progression of NAFLD to HCC is closely associated with paracrine communication among hepatic cells. Vascular endothelial growth factor A (VEGFA) plays a key role in NAFLD and HCC; however, the cellular communication of VEGFA in the pathological transition from NAFLD to HCC remains unclear. Here, we found that VEGFA elevation was considerably distributed in hepatocytes of clinical and murine NAFLD-HCC specimens. Notably, progression from NAFLD to HCC was attenuated in hepatocyte-specific deletion of Vegfa (VegfaΔhep) mice. Mechanistically, VEGFA activated human hepatic stellate cell (HSC) LX2 into a fibrogenic phenotype via VEGF-VEGFR signaling in fatty acid medium, and HSC activation was largely attenuated in VegfaΔhep mice during NAFLD-HCC progression. Additionally, a positive correlation between VEGFA and hepatic fibrosis was observed in the NAFLD-HCC cohort, but not in the HBV-HCC cohort. Moreover, LX2 cells could be activated by conditioned medium from NAFLD-derived organoids, but not from HBV livers, whereas this activation was blocked by a VEGFA antibody. In summary, our findings reveal that hepatocyte-derived VEGFA contributes to NAFLD-HCC development by activating HSCs and highlight the potential of precisely targeting hepatocytic VEGFA as a promising therapeutic strategy for NAFLD-HCC.

The clinical effectiveness and safety of using epidermal growth factor, fibroblast growth factor and granulocyte-macrophage colony stimulating factor as therapeutics in acute skin wound healing: a systematic review and meta-analysis.

Background: Promoting wound healing is crucial to restore the vital barrier function of injured skin. Growth factor products including epidermal growth factor (EGF), fibroblast growth factor (FGF) and granulocyte-macrophage colony stimulating factor (GM-CSF) have been used for decades although no systematic evaluation exists regarding their effectiveness and safety issues in treating acute skin wounds. This has resulted in a lack of guidelines and standards for proper application regimes. Therefore, this systematic review and meta-analysis was performed to critically evaluate the effectiveness and safety of these growth factors on skin acute wounds and provide guidelines for application regimes. Methods: We searched PubMed/Medline (1980-2020), Cochrane Library (1980-2020), Cochrane CENTRAL (from establishment to 2020), ClinicalTrials.gov (from establishment to 2020), Chinese Journal Full-text Database (CNKI, 1994-2020), China Biology Medicine disc (CBM, 1978-2019), Chinese Scientific Journal Database (VIP, 1989-2020) and Wanfang Database (WFDATA, 1980-2019). Randomized controlled trials (RCTs), quasi-RCTs and controlled clinical trials treating patients with acute skin wounds from various causes and with those available growth factors were included. Results: A total of 7573 papers were identified through database searching; 229 papers including 281 studies were kept after final screening. Administering growth factors significantly shortened the healing time of acute skin wounds, including superficial burn injuries [mean difference (MD) = -3.02; 95% confidence interval (CI):-3.31 ~ -2.74; p < 0.00001], deep burn injuries (MD = -5.63; 95% CI:-7.10 ~ -4.17; p < 0.00001), traumata and surgical wounds (MD = -4.50; 95% CI:-5.55 ~ -3.44; p < 0.00001). Growth factors increased the healing rate of acute skin wounds and decreased scar scores. The incidence of adverse reactions was lower in the growth factor treatment group than in the non-growth factor group. Conclusions: The studied growth factors not only are effective and safe for managing acute skin wounds, but also accelerate their healing with no severe adverse reactions.

Sintilimab plus chemotherapy achieved symptom relief in stage IV lung squamous cell carcinoma with superior vena cava syndrome: a case report.

Lung cancer is the second most common and mortality disease in the world. Most patients with lung cancer are already at the advanced stage when diagnosed. There are multiple treatments for advanced lung cancer. Among them, immunotherapy plus chemotherapy has gradually become the first-line treatment. Lung cancer has multiple complications, superior vena cava syndrome (SVCS) is a common complication of patients with advanced lung cancer. The current treatments include radiotherapy, chemotherapy, and stent implantation. Stent implantation has the disadvantages of invasiveness and poor efficacy. Immunotherapy, as an emerging treatment for tumors, has shown significant advantages in treating patients with advanced lung cancer. However, the treatment of advanced lung cancer with SVCS using immunotherapy has rarely been reported. Here, we reported a 48-year-old male patient with stage IV (T4N3M1) lung squamous cell carcinoma. After receiving 1 cycle (3 weeks) of comprehensive treatment with sintilimab plus chemotherapy, the tumor mass shrank by 30% to achieve partial response (PR), collateral circulation was formed, and most of the symptoms caused by SVCS disappeared. After 3 cycles of treatment, the tumor shrank by nearly 90%, and the superior and inferior vena cava opened larger than before. Our case provides a novel treatment strategy for such patients.

Towards Efficient Visual Simplification of Computational Graphs in Deep Neural Networks.

A computational graph in a deep neural network (DNN) denotes a specific data flow diagram (DFD) composed of many tensors and operators. Existing toolkits for visualizing computational graphs are not applicable when the structure is highly complicated and large-scale (e.g., BERT [1]). To address this problem, we propose leveraging a suite of visual simplification techniques, including a cycle-removing method, a module-based edge-pruning algorithm, and an isomorphic subgraph stacking strategy. We design and implement an interactive visualization system that is suitable for computational graphs with up to 10 thousand elements. Experimental results and usage scenarios demonstrate that our tool reduces 60% elements on average and hence enhances the performance for recognizing and diagnosing DNN models. Our contributions are integrated into an open-source DNN visualization toolkit, namely, MindInsight [2].