Microbiome dysbiosis occurred in hypertrophic scars is dominated by S. aureus colonization

BackgroundThe mechanisms of hypertrophic scar formation and its tissue inflammation remain unknown.MethodsWe collected 33 hypertrophic scar (HS) and 36 normal skin (NS) tissues, and detected the tissue inflammation and bacteria using HE staining, Gram staining, and transmission electronic microscopy (TEM), in situ hybridization and immunohistochemistry for MCP-1, TNF-α, IL-6 and IL-8. In addition, the samples were assayed by 16S rRNA sequencing to investigate the microbiota diversity in HS, and the correlation between the microbiota and the indices of Vancouver Scar Scale(VSS)score.ResultsHE staining showed that a dramatically increased number of inflammatory cells accumulated in HS compared with NS, and an enhanced number of bacteria colonies was found in HS by Gram staining, even individual bacteria could be clearly observed by TEM. In situ hybridization demonstrated that the bacteria and inflammation cells co-localized in the HS tissues, and immunohistochemistry indicated the expression of MCP-1, TNF-α, IL-6, and IL-8 were significantly upregulated in HS than that in NS. In addition, there was a significantly different microbiota composition between HS and NS. At the phylum level, Firmicutes was significantly higher in HS than NS. At the genus level, S. aureus was the dominant species, which was significantly higher in HS than NS, and was strongly correlated with VSS indices.ConclusionMicrobiome dysbiosis, dominated by S. aureus, occurred in HS formation, which is correlated with chronic inflammation and scar formation, targeting the microbiome dysbiosis is perhaps a supplementary way for future scar management

Huobahuagen tablet improves renal function in diabetic kidney disease: a real-world retrospective cohort study

ObjectiveWe aimed to explore the value of Huobahuagen tablet (HBT) in improving decreased renal function for patients with diabetic kidney disease (DKD) over time.MethodsThis was a single-center, retrospective, real-world study on eligible 122 DKD patients who continued to use HBT + Huangkui capsule (HKC) therapy or HKC therapy without interruption or alteration in Jiangsu Province Hospital of Chinese Medicine from July 2016 to March 2022. The primary observation outcomes included estimated glomerular filtration rate (eGFR) at baseline and 1-, 3-, 6-, 9-, and 12-month follow-up visits and changes in eGFR from baseline (ΔeGFR). Propensity score (PS) and inverse probability treatment weighting (IPTW) were used to control for confounders.ResultseGFR was significantly higher in the HBT + HKC group than in the HKC alone group at the 6-, 9-, and 12-month follow-up visits (p = 0.0448, 0.0002, and 0.0037, respectively), indicating the superiority of HBT + HKC over HBT alone. Furthermore, the ΔeGFR of the HBT + HKC group was significantly higher than that of the HKC alone group at the 6- and 12-month follow-up visits (p = 0.0369 and 0.0267, respectively). In the DKD G4 patients, eGFR was higher in the HBT + HKC group at the 1-, 3-, 6-, 9-, and 12-month follow-up visits compared with baseline, with statistically significant differences at the 1-, 3-, and 6- month follow-up visits (p = 0.0256, 0.0069, and 0.0252, respectively). The fluctuations in ΔeGFR ranged from 2.54 ± 4.34 to 5.01 ± 5.55 ml/min/1.73 m2. Change in the urinary albumin/creatinine ratio from baseline did not exhibit a significant difference between the two groups at any of the follow-up visits (p > 0.05 for all). Adverse event incidence was low in both groups.ConclusionThe findings of this study based on real-world clinical practice indicate that HBT + HKC therapy exhibited better efficacy in improving and protecting renal function with a favorable safety profile than HKC therapy alone. However, further large-scale prospective randomized controlled trials are warranted to confirm these results

GLP-1RAs caused gastrointestinal adverse reactions of drug withdrawal: a system review and network meta-analysis

BackgroundGlucagon-like peptide-1 receptor agonists (GLP-1RAs) significantly reduce postprandial blood glucose, inhibit appetite, and delay gastrointestinal emptying. However, it is controversial that some patients are intolerant to GLP-1RAs.MethodsPubMed, Embase, Web of Science, and Cochrane Library were searched for randomized controlled trials (RCTs) using GLP-1RAs with documented withdrawal due to gastrointestinal adverse reactions (GI AEs) from their inception to September 28, 2022. After extracting the information incorporated into the studies, a random-effects network meta-analysis was performed within a frequentist framework.Results64 RCTs were finally enrolled, which included six major categories of the GLP-1RA. The sample size of the GLP-1RAs treatment group was 16,783 cases. The risk of intolerable gastrointestinal adverse reactions of Liraglutide and Semaglutide was higher than that of Dulaglutide. Meanwhile, the higher the dose of the same GLP-1RA preparation, the more likely to cause these adverse reactions. These intolerable GI AEs were not significantly related to drug homology or formulations and may be related to the degree of suppression of the appetite center.ConclusionDulaglutide caused the lowest intolerable GI AEs, while Liraglutide and Semaglutide were the highest. For Semaglutide, the higher the dose, the more likely it is to drive GI AEs. Meanwhile, the risk of these GI AEs is independent of the different formulations of the drug. All these findings can effectively guide individualized treatment.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022359346, identifier CRD42022359346

Influencing factors of the high-quality economic development in China based on LASSO model

This paper constructs an index system for high-quality economic development in China from four dimensions: economic system, social system, environment system, and power system. The LASSO method was presented as screen indicators, then we use the panel fixed effect model to investigate the specific impact of key factors on high-quality economic development. The results indicate that: (1) Innovation-driven, infrastructure construction, green technology development, power supply, and efficient utilization of electrical equipment are the most important influencing factors to promote high-quality economic development. (2) Increasing financial expenditures for pollution prevention and control and strengthening the application of green technology will help to adjust the economic structure. (3) Building a complete green energy system will be an essential part of high-quality economic development. On this basis, heterogeneity analysis is carried out according to regional economic differences and power supply and demand positioning. These findings have great significance in high-quality economic development of China

Dynamic assessment of the carbon-neutral process based on FDA method

In this paper, the carbon-neutral process is constructed to measure the development level of a low-carbon economy in 30 provinces of China. The entropy weight method is used to measure the carbon neutralization level. The Functional Data Analysis and various curves are used to investigate potential dynamic changes. Finally, the heterogeneity analysis is carried out on the sample provinces. We find: (1) The carbon-neutral process’s performance of provinces is significantly different in China, the top three are: Guangzhou (0.6556), Shanghai (0.5559), Jiangsu (0.5095), and the last three are: Xinjiang (0.1583), Gansu (0.1475), Guizhou (0.1453); (2) The carbon-neutral process’s performance in China shows an obvious upward trend and the growth rate has usually been positive; (3) Through heterogeneity analysis, the performance of carbon neutralization process is different in the five regions. But all regions are currently in an upswing or recovery phase. These findings are significant for China to achieve’Carbon Peak in 2030, Carbon Neutrality in 2060’ as scheduled

Semi-Analytic Solution of Multiple Inhomogeneous Inclusions and Cracks in an Infinite Space

This work develops a semi-analytic solution for multiple inhomogeneous inclusions of arbitrary shape and cracks in an isotropic infinite space. The solution is capable of fully taking into account the interactions among any number of inhomogeneous inclusions and cracks which no reported analytic or semi-analytic solution can handle. In the solution development, a novel method combining the equivalent inclusion method (EIM) and the distributed dislocation technique (DDT) is proposed. Each inhomogeneous inclusion is modeled as a homogenous inclusion with initial eigenstrain plus unknown equivalent eigenstrain using the EIM, and each crack of mixed modes I and II is modeled as a distribution of edge climb and glide dislocations with unknown densities. All the unknown equivalent eigenstrains and dislocation densities are solved simultaneously by means of iteration using the conjugate gradient method (CGM). The fast Fourier transform algorithm is also employed to greatly improve computational efficiency. The solution is verified by the finite element method (FEM) and its capability and generality are demonstrated through the study of a few sample cases. This work has potential applications in reliability analysis of heterogeneous materials.ASTAR (Agency for Sci., Tech. and Research, S’pore

Phosphorylation: new star of pathogenesis and treatment in steatotic liver disease

Abstract Steatotic liver disease poses a serious threat to human health and has emerged as one of the most significant burdens of chronic liver disease worldwide. Currently, the research mechanism is not clear, and there is no specific targeted drug for direct treatment. Phosphorylation is widely regarded as the most common type of protein modification, closely linked to steatotic liver disease in previous studies. However, there is no systematic review to clarify the relationship and investigate from the perspective of phosphorylation. Phosphorylation has been found to mainly regulate molecule stability, affect localization, transform molecular function, and cooperate with other protein modifications. Among them, adenosine 5’-monophosphate-activated protein kinase (AMPK), serine/threonine kinase (AKT), and nuclear factor kappa-B (NF-kB) are considered the core mechanisms in steatotic liver disease. As to treatment, lifestyle changes, prescription drugs, and herbal ingredients can alleviate symptoms by influencing phosphorylation. It demonstrates the significant role of phosphorylation as a mechanism occurrence and a therapeutic target in steatotic liver disease, which could be a new star for future exploration