Fatty acid binding protein 4 (FABP4) induces chondrocyte degeneration via activation of the NF-κb signaling pathway.

The pathogenesis of osteoarthritis (OA) is still unclear. Fatty acid binding protein 4 (FABP4), a novel adipokine, has been found to play a role in OA. This study aimed to explore the role of NF-κB in FABP4-induced OA. In the in vivo study, four pairs of 12-week-old male FABP4 knockout (KO) and wild-type (WT) mice were included. The activation of NF-κB was assessed. In parallel, 24 6-week-old male C57/Bl6 mice were fed a high-fat diet (HFD) and randomly allocated to four groups: daily oral gavage with (1) PBS solution; (2) QNZ (NF-κB-specific inhibitor, 1 mg/kg/d); (3) BMS309403 (FABP4-specific inhibitor, 30 mg/kg/d); and (4) BMS309403 (30 mg/kg/d) + QNZ (1 mg/kg/d). The diet and treatment were sustained for 4 months. The knee joints were obtained to assess cartilage degradation, NF-κB activation, and subchondral bone sclerosis. In the in vitro study, a mouse chondrogenic cell line (ATDC5) was cultured. FABP4 was supplemented to stimulate chondrocytes, and the activation of NF-κB was investigated. In parallel, QNZ and NF-κB-specific siRNA were used to inhibit NF-κB. In vivo, the FABP4 WT mice had more significant NF-κB activation than the KO mice. Dual inhibition of FABP4 and NF-κB alleviated knee OA in mice. FABP4 has no significant effect on the activation of the JNK signaling pathway. In vitro, FABP4 directly activated NF-κB in chondrocytes. The use of QNZ and NF-κB-siRNA significantly alleviated the expression of catabolic markers of chondrocytes induced by FABP4. FABP4 induces chondrocyte degeneration by activating the NF-κB pathway.

Host specificity of plant-associated bacteria is negatively associated with genome size and host abundance along a latitudinal gradient.

Host specialization plays a critical role in the ecology and evolution of plant-microbe symbiosis. Theory predicts that host specialization is associated with microbial genome streamlining and is influenced by the abundance of host species, both of which can vary across latitudes, leading to a latitudinal gradient in host specificity. Here, we quantified the host specificity and composition of plant-bacteria symbioses on leaves across 329 tree species spanning a latitudinal gradient. Our analysis revealed a predominance of host-specialized leaf bacteria. The degree of host specificity was negatively correlated with bacterial genome size and the local abundance of host plants. Additionally, we found an increased host specificity at lower latitudes, aligning with the high prevalence of small bacterial genomes and rare host species in the tropics. These findings underscore the importance of genome streamlining and host abundance in the evolution of host specificity in plant-associated bacteria along the latitudinal gradient.

TRPV1+ neurons alter Staphylococcus aureus skin infection outcomes by affecting macrophage polarization and neutrophil recruitment.

BACKGROUND: The interaction between the nervous system and the immune system can affect the outcome of a bacterial infection. Staphylococcus aureus skin infection is a common infectious disease, and elucidating the relationship between the nervous system and immune system may help to improve treatment strategies. RESULTS: In this study, we found that the local release of calcitonin gene-related peptide (CGRP) increased during S. aureus skin infection, and S. aureus could promote the release of CGRP from transient receptor potential cation channel subfamily V member 1 (TRPV1+) neurons in vitro. The existence of TRPV1+ neurons inhibited the recruitment of neutrophils to the infected region and regulated the polarization of macrophages toward M2 while inhibiting polarization toward M1. This reduces the level of inflammation in the infected area, which aggravates the local infection. Furthermore, this study demonstrates that TRPV1 may be a target for the treatment of S. aureus skin infections and that botulinum neurotoxin A (BoNT/A) and BIBN4096 may reverse the inhibited inflammatory effect of CGRP, making them potential therapeutics for the treatment of skin infection in S. aureus. CONCLUSIONS: In S. aureus skin infection, TRPV1+ neurons inhibit neutrophil recruitment and regulate macrophage polarization by releasing CGRP. BoNT/A and BIBN4096 may be potential therapeutic agents for S. aureus skin infection.

Diversity and biogeography of plant phyllosphere bacteria are governed by latitude-dependent mechanisms.

Predicting and managing the structure and function of plant microbiomes requires quantitative understanding of community assembly and predictive models of spatial distributions at broad geographic scales. Here, we quantified the relative contribution of abiotic and biotic factors to the assembly of phyllosphere bacterial communities, and developed spatial distribution models for keystone bacterial taxa along a latitudinal gradient, by analyzing 16S rRNA gene sequences from 1453 leaf samples taken from 329 plant species in China. We demonstrated a latitudinal gradient in phyllosphere bacterial diversity and community composition, which was mostly explained by climate and host plant factors. We found that host-related factors were increasingly important in explaining bacterial assembly at higher latitudes while nonhost factors including abiotic environments, spatial proximity and plant neighbors were more important at lower latitudes. We further showed that local plant-bacteria associations were interconnected by hub bacteria taxa to form metacommunity-level networks, and the spatial distribution of these hub taxa was controlled by hosts and spatial factors with varying importance across latitudes. For the first time, we documented a latitude-dependent importance in the driving factors of phyllosphere bacteria assembly and distribution, serving as a baseline for predicting future changes in plant phyllosphere microbiomes under global change and human activities.

A mechanistic model for nitrogen-limited plant growth.

BACKGROUND AND AIMS: Nitrogen is often regarded as a limiting factor to plant growth in various ecosystems. Understanding how nitrogen drives plant growth has numerous theoretical and practical applications in agriculture and ecology. In 2004, Göran I. Ågren proposed a mechanistic model of plant growth from a biochemical perspective. However, neglecting respiration and assuming stable and balanced growth made the model unrealistic for plants growing in natural conditions. The aim of the present paper is to extend Ågren's model to overcome these limitations. METHODS: We improved Ågren's model by incorporating the respiratory process and replacing the stable and balanced growth assumption with a three-parameter power function to describe the relationship between nitrogen concentration (Nc) and biomass. The new model was evaluated based on published data from three studies on corn (Zea mays) growth. KEY RESULTS: Remarkably, the mechanistic growth model derived in this study is mathematically equivalent to the classical Richards model, which is the most widely used empirical growth model. The model agrees well with empirical plant growth data. CONCLUSIONS: Our model provides a mechanistic interpretation of how nitrogen drives plant growth. It is very robust in predicting growth curves and the relationship between Nc and relative growth rate.

Traditional use and safety evaluation of combination Traditional Chinese Medicine in European registration: with XiaoYao Tablets as an example.

Mental health disorders such as stress, anxiety, depression and insomnia caused by COVID-19 have attracted worldwide attention. Traditional Chinese medicines (TCMs) have been proven to be a safe and effective option for treating mental health disorders. Recently, after assessing its efficacy and safety fully, the Netherlands Medicines Evaluation Board approved XiaoYao Tablets as a traditional herbal medicinal product (THMP), indicated for an alternative self-care for patients in Europe to relieve the symptoms of mental stress and exhaustion. Despite the fact that TCMs have gradually become one of the therapeutic choices worldwide, to-date, only a few TCMs have been successfully registered in the European Union (EU) as THMPs, and XiaoYao Tablets is the first successfully registered combination TCM from China. In this article, traditional use efficacy and clinical safety of XiaoYao Tablets in the treatment of mental health disorders were summarized and analyzed from the perspective of traditional use registration (TUR). Additionally a safety evolution pathway of combination TCMs was established. This article will not only seek to enhance our understanding about traditional use efficacy and clinical safety of XiaoYao Tablets, but also summarize the experience of XiaoYao Tablets as the first successfully registered combination TCM from China, which could serve as role model for the others to overcome registration difficulties in the EU.

The complexity of trait-environment performance landscapes in a local subtropical forest.

That functional traits should affect individual performance and, in turn, determine fitness and population growth, is a foundational assumption of trait-based ecology. This assumption is, however, not supported by a strong empirical base. Here, we measured simultaneously two individual performance metrics (survival and growth), seven traits and 10 environmental properties for each of 3981 individuals of 205 species in a 50-ha stem-mapped subtropical forest. We then modelled survival/growth as a function of traits, environments and trait × environment interactions, and quantified their relative importance at both the species and individual levels. We found evidence of alternative functional designs and multiple performance peaks along environmental gradients, indicating the presence of complicated trait × environment interactions. However, such interactions were relatively unimportant in our site, which had relatively low environmental variations. Moreover, individual performance was not better predicted, and trait × environment interactions were not more likely detected, at the individual level than at the species level. Although the trait × environment interactions might be safely ignored in relatively homogeneous environments, we encourage future studies to test the interactive effects of traits and environments on individual performances and lifelong fitness at larger spatial scales or along experimentally manipulated environmental gradients.

Direct effects of selection on aboveground biomass contrast with indirect structure-mediated effects of complementarity in a subtropical forest.

Understanding the multiple biotic and abiotic controls of aboveground biomass (AGB) is important for projecting the consequences of global change and to effectively manage carbon storage. Although large-scale studies have identified the major environmental and biological controls of AGB, drivers of local-scale variation are less well known. Additionally, involvement of multiple causal paths and scale dependence in effect sizes potentially confounds comparisons among studies differing in methodology and sampling grain. We tested for scale dependence in evidence supporting selection, complementarity and environmental factors as the main determinants of AGB variation over a 50 ha study extent in subtropical China, modelling this at four sampling grains (0.01, 0.04, 0.25 and 1 ha). At each grain, we used piecewise structural equation models to quantify the direct and indirect effects of environmental (topographic and edaphic properties) and forest attributes (structure, diversity and functional traits) on AGB, while controlling for spatial autocorrelation. Direct scale-invariant effects on AGB were evident for structure and community-mean traits, supporting dominance of selection effects. However, diversity had strong indirect effects on AGB via forest structure, particularly at larger sampling grains (≥ 0.25 ha), while direct effects only emerged at the smallest grain size (0.01 ha). The direct and indirect effects of edaphic and topographic factors were also important for explaining both forest attributes and AGB across all scales. Although selection effects appeared to be more influential on ecosystem function, ignoring indirect causal pathways for diversity via structural attributes risks overlooking the importance of complementarity on ecosystem functioning, particularly as sampling grain increases.

Impact of CPAP treatment for obstructive sleep apnea on visceral adipose tissue: a meta-analysis of randomized controlled trials.

BACKGROUND: It is still controversial if the continuous positive airway pressure (CPAP) treatment for patients with obstructive sleep apnea (OSA) can markedly influence an effect on visceral adipose tissue (VAT). The current study aimed to assess the efficacy of CPAP interventions in reducing VAT in OSA patients. METHODS: The Web of Science, PubMed, Embase, and Cochrane Library (up to December, 2019) were searched for randomized trials that assessed the effect of CPAP therapy in decreasing VAT in OSA patients. Information on the study, pre- and post-CPAP treatment of VAT, and patient characteristics were extracted for analysis. The standardized mean difference (SMD) was applied to measure the summary estimates. The analysis was conducted with STATA 13.0 and RevMan v.5.3. RESULTS: Five studies (6 cohorts) that involved 169 patients were enrolled in the meta-analysis. There was no significant change of VAT in patients with OSA before and after CPAP treatment (SMD = - 0.00, 95% CI = - 0.21 to 0.21, z = 0.01, p = 0.99). Subgroup analyses further demonstrated that the results were not influenced by CPAP therapy duration, patient age, sample size, or baseline body mass index. CONCLUSIONS: Among the patients with OSA, our meta-analysis revealed that treatment with CPAP does not significantly lead to a reduction of VAT. High-quality randomized controlled trials may provide further clarifying information.

The role of circRNA derived from RUNX2 in the serum of osteoarthritis and its clinical value.

BACKGROUND: Circular RNA (circRNA) has been shown to affect the pathological process of osteoarthritis (OA) and is expected to become a potential marker for disease diagnosis. This study aimed to investigate the association between circRNA derived from the gene of runt-related transcription factor 2 (RUNX2) and OA risk. METHODS: The expression profile of RUNX2-derived circRNAs in serum of OA patients was detected. Then, the cytological localization of screened differential circRNAs was studied. Luciferase (LUC) reporter assay was used to identify the microRNA (miRNA) sponge capacity of the circRNAs. Bioinformatics analysis was used to construct the functional pathway of this circRNA-miRNAs network. And then, the diagnostic value of RUNX2-derived circRNAs in OA was evaluated. RESULTS: RUNX2-derived hsa_circ_0005526 (circ_RUNX2) is significantly highly expressed in OA serum and mainly located in the cytoplasm within the cartilage cell by sponging multiple miRNAs (miR-498, miR-924, miR-361-3p, and miR-665). Bioinformatics analysis showed ECM-receptor interaction pathway ranked the most significant pathway of circ_RUNX2-miRNAs regulatory network in KEGG database. The ROC curve showed that there may be good diagnostic value of serum circ_RUNX2 in OA. CONCLUSION: RUNX2-derived circ_RUNX2 may be involved in OA development via ECM-receptor interaction pathways and may be used as potential clinical indicator of OA.

Intra- and interspecific trait variations reveal functional relationships between specific leaf area and soil niche within a subtropical forest.

Background and Aims: How functional traits vary with environmental conditions is of fundamental importance in trait-based community ecology. However, how intraspecific variability in functional traits is connected to species distribution is not well understood. This study investigated inter- and intraspecific variation of a key functional trait, i.e. specific leaf area (leaf area per unit dry mass; SLA), in relation to soil factors and tested if trait variation is more closely associated with specific environmental regimes for low-variability species than for high-variability species. Methods: In a subtropical evergreen forest plot (50 ha, southern China), 106 700 leaves from 5335 individuals of 207 woody species were intensively collected, with 30 individuals sampled for most species to ensure a sufficient sample size representative of intraspecific variability. Soil conditions for each plant were estimated by kriging from more than 1700 observational soil locations across the plot. Intra- and interspecific variation in SLA were separately related to environmental factors. Based on the species-specific variation of SLA, species were categorized into three groups: low-, intermediate- and high-intraspecific variability. Intraspecific habitat ranges and the strength of SLA-habitat relationships were compared among these three groups. Key Results: Interspecific variation in SLA overrides the intraspecific variation (77 % vs. 8 %). Total soil nitrogen (TN, positively) and total organic carbon (TOC, negatively) are the most important explanatory factors for SLA variation at both intra- and interspecific levels. SLA, both within and between species, decreases with decreasing soil nitrogen availability. As predicted, species with low intraspecific variability in SLA have narrower habitat ranges with respect to soil TOC and TN and show a stronger SLA-habitat association than high-variability species. Conclusions: For woody plants low SLA is a phenotypic and probably adaptive response to nitrogen stress, which drives the predominance of species with ever-decreasing SLA towards less fertile habitats. Intraspecific variability in SLA is positively connected to species' niche breadth, suggesting that low-variability species may play a more deterministic role in structuring plant assemblages than high-variability species. This study highlights the importance of quantifying intraspecific trait variation to improve our understanding of species distributions across a vegetated landscape.

Association Between Suboptimal Health Status and Health-Related Productivity Loss in Primary Healthcare Workers in China: a Cross-Sectional Survey.

Objective: This study aimed to clarify the association between suboptimal health status and health-related productivity loss among primary healthcare workers in China. Material and Methods: A field questionnaire survey was conducted with a multistage sampling among primary healthcare workers. The data on sub-health and health-related productivity loss were collected using the Sub-health Measurement Scale Version 1.0 and Work Productivity and Activity Impairment Questionnaire: General Health, respectively. Ordinary least squares regression was used to evaluate the association of the suboptimal health and health-related productivity loss. Subgroup analyses were performed by occupation (physician and nurse). Results: Front-line primary healthcare workers (N = 1709) from 31 provinces in China responded to the survey. Of all participants, 73.43% experienced suboptimal health. The status of being in physical suboptimal health (Coef. = 0.050, p < 0.001, 95% CI = [0.031,0.070]) and mental suboptimal health (Coef. = 0.040, p < 0.001, 95% CI = [0.020,0.059]) status exerted significant effect on the extent of health-related productivity loss among primary healthcare workers in China. Nurses in social adaptation suboptimal health status (Coef. = 0.030, p = 0.027, 95% CI = [0.003,0.057]) had significant effect on health-related productivity loss. Conclusion: The prevalence of suboptimal health is high among the respondents. Providing support for primary healthcare workers from bio-psycho-social aspects is an effective measure to promote their occupational health and improve their productivity.

Discussion of the classification of pediatric drug clinical trials in children's hospitals in China.

Objectives: This study aimed to gain insights into pediatric clinical trials conducted in children's hospitals in China and provide valuable references for the development of children's hospitals and the research and development of pediatric drugs. Methods: A comprehensive search was performed on the Chinese Clinical Trial Registry (Chi CTR) and ChinaDrugTrials.org.cn to collect information on all clinical trials involving subjects under 18 years, including those conducted in children's hospitals. The retrieval period was extended until 31 December 2022. Results: A total of 459 pediatric clinical trials were collected, comprising 299 from Chi CTR and 160 from the Drug Clinical Trial Registration and Information Publicity Platform (Information Platform). Post-marketing drug studies and phase III clinical trials accounted for the majority of research stages. These trials covered a wide range of diseases/systems, with a particular focus on respiratory system disorders, tumors, endocrine disorders, and nutritional or metabolic diseases. Chemical drugs constituted the most extensively studied category, while traditional Chinese medicine/natural drugs received comparatively less attention. Clinical trial activities were primarily geographically focused on the eastern coastal regions of China, with multicenter trials being the most predominant. Ethics committee approval was obtained for 427 studies. Conclusion: The pediatric clinical trials conducted by children's hospitals in China have shown an overall upward trend; however, there is limited research focusing on traditional Chinese medicine, along with significant regional and institutional imbalances. Furthermore, there is still room for improvement regarding ethical review processes. It is recommended that children's hospitals enhance their scientific research capabilities while optimizing resource allocation to meet medical service demands effectively. Additionally, fostering more research-focused children's hospitals will contribute to the high-quality development of children's health in China.

Effectiveness, cost, and safety of four regimens recommended by WHO for RR/MDR-TB treatment: a cohort study in Eastern China.

BACKGROUND: To compare the effectiveness, cost, and safety of four regimens recommended by the World Health Organization (WHO) for rifampicin resistance/multidrug-resistance tuberculosis (RR/MDR-TB) Treatment in Eastern China. METHODS: We performed a cohort study among patients with RR/MDR between 2020 and 2022 in Jiangsu Province. The treatment success rate, cost, and drug adverse reaction rate were compared. RESULTS: Between 2020 and 2022, 253 RR/MDR-TB patients were enrolled in the study. 37 (14.62%), 76 (30.04%), 74 (29.25%), and 66 (26.09%) patients had the short-term regimens, the new long-term oral regimens, the new long-term injectable regimens, and the traditional long-term regimens, respectively. The treatment success rate was the highest among patients treated with the short-term regimen (75.68%) and was the lowest among patients treated with the traditional long-term regimens (60.61%). The estimated mean cost per favorable outcome was 142.61 thousand Chinese Yuan (CNY), and the short-term regimens showed the lowest cost in the four regimes (88.51 thousand CNY vs. 174.24 thousand CNY, 144.00 thousand CNY, and 134.98 thousand CNY). Incremental cost-effectiveness ratios of the short-term regimens, the new long-term oral regimen, and the new long-term injectable regimens were -3083.04, 6040.09, and 819.68 CNY compared to the traditional long-term regimens. CONCLUSIONS: For RR/MDR-TB patients in China who meet the criteria for short-term regimens, the short-term regimens were proven to be the most cost-effective of the four regimens recommended by WHO. For RR/MDR-TB patients in China who don't meet the criteria for short-term regimens, the new long-term injectable regimens are more cost-effective than the remaining two regimens.

This is the first study to evaluate the effectiveness, cost, and safety of four regimens recommended by the WHO for RR/MDR-TB treatment in China.For RR/MDR-TB patients in China who meet the criteria for the short-term regimens, the short-term regimens were proven to be the most cost-effective of the four regimens recommended by WHO.

Improved cure rate of periprosthetic joint infection through targeted antibiotic therapy based on integrated pathogen diagnosis strategy.

Objectives: This study aimed to determine whether combined of pathogen detection strategies, including specimen acquisition, culture conditions, and molecular diagnostics, can improve treatment outcomes in patients with periprosthetic joint infections (PJI). Methods: This retrospective study included suspected PJI cases from three sequential stages at our institution: Stage A (July 2012 to June 2015), Stage B (July 2015 to June 2018), and Stage C (July 2018 to June 2021). Cases were categorized into PJI and aseptic failure (AF) groups based on European Bone and Joint Infection Society (EBJIS) criteria. Utilization of pathogen diagnostic strategies, pathogen detection rates, targeted antibiotic prescription rates, and treatment outcomes were analyzed and compared across the three stages. Results: A total of 165 PJI cases and 38 AF cases were included in this study. With the progressive implementation of the three optimization approaches across stages A, B and C, pathogen detection rates exhibited a gradual increase (χ2 = 8.282, P=0.016). Similarly, utilization of targeted antibiotic therapy increased stepwise from 57.1% in Stage A, to 82.3% in Stage B, and to 84% in Stage C (χ2 = 9.515, P=0.009). The 2-year infection control rate exceeded 90% in both stages B and C, surpassing stage A (71.4%) (χ2 = 8.317, P=0.011). Combined application of all three optimized protocols yielded the highest sensitivity of 91.21% for pathogen detection, while retaining higher specificity of 92.11%. Conclusion: The utilization of combined pathogen diagnostic strategies in PJI can increase pathogen detection rates, improve targeted antibiotic prescription, reduce the occurrence of antibiotic complications, and achieve better treatment outcomes.

Cost-effectiveness of camrelizumab plus chemotherapy vs. chemotherapy in the first-line treatment of non-squamous NSCLC: Evidence from China.

Objective: We aimed to evaluate the cost-effectiveness of camrelizumab plus chemotherapy compared with chemotherapy alone as the first-line treatment for patients with metastatic or advanced non-squamous non-small cell lung cancer (NSCLC) without targetable epidermal growth factor receptor or anaplastic lymphoma kinase genetic aberrations in patients in China. Methods: A partitioned survival model was constructed to estimate the cost-effectiveness of camrelizumab plus chemotherapy vs. chemotherapy in the first-line treatment of non-squamous NSCLC from a Chinese healthcare perspective. Survival analysis was performed to calculate the proportion of patients in each state using data from trial NCT03134872. The cost of drugs was obtained from Menet, and the cost of disease management was obtained from local hospitals. Health state data were obtained from published literature. Both deterministic sensitivity analyses (DSA) and probabilistic sensitivity analysis (PSA) were adopted to verify the robustness of the results. Results: Compared with chemotherapy alone, camrelizumab plus chemotherapy provided 0.41 incremental quality-adjusted life years (QALYs) at an incremental cost of $10,482.12. Therefore, the incremental cost-effectiveness ratio of camrelizumab plus chemotherapy was $25,375.96/QALY from the Chinese healthcare perspective, much lower than three times the GDP per capita of China in 2021 ($35,936.09) as the willingness-to-pay threshold. The DSA indicated that the incremental cost-effectiveness ratio was most sensitive to the utility value of progression-free survival, followed by the cost of camrelizumab. The PSA illustrated that camrelizumab had 80% probability of being cost-effective at the threshold of $35,936.09 per QALY gained. Conclusion: The results suggest that camrelizumab plus chemotherapy is a cost-effective choice in the first-line treatment for patients with non-squamous NSCLC in China. Although this study has limitations such as short time of use of camrelizumab, no adjustment of Kaplan-Meier curves and the median overall survival that has not been reached, the difference in results caused by these factors is relatively small.

Trait-mediated leaf retention of atmospheric particulate matter in fourteen tree species in southern China.

Particulate air pollution is a serious threat to human health, especially in urban areas, and trees can act as biological filters and improve air quality. However, studies on greening tree species selection are rare. We measured three particular matter adsorption metrics (PM2.5, PM2.5-10, and PM>10 captured per leaf area) and six functional traits for each of fourteen species and estimated their minimum light requirements based on field surveys. We found that shade-tolerant species captured more coarse particles (PM2.5-10) than light-demanding species. For traits, a strong negative correlation was found between photosynthetic capacity and adsorption capacity for all three PM size fractions, indicating that in comparison to acquisitive species, conservative species captured larger amounts of particles. Moreover, denser wood species and smaller leaves were more efficient in capturing large particles (PM>10), while species with "expensive" leaves (high leaf N or P) were more efficient in capturing fine particles (PM2.5), indicating that capturing large and fine particles was related to mechanical stability traits and leaf surface traits, respectively. Our results demonstrated that the metabolism (e.g., photosynthetic capacity) and chemistry (e.g., leaf N and leaf P) of leaves help explain species capacity to capture PM. We encourage future studies to investigate the ecosystem functions and stress tolerance of tree species with the same framework and trait-based methods.

Motor neurons transplantation alleviates neurofibrogenesis during chronic degeneration by reversibly regulating Schwann cells epithelial-mesenchymal transition.

A novel understanding of peripheral nerve injury is epithelial-mesenchymal transition (EMT), which characterizes the process of dedifferentiation and transformation of Schwann cells after nerve injury. Despite being regarded as an important mechanism for healing nerve injuries, long-term EMT is the primary cause of fibrosis in other tissue organs. The potential mechanism promoting neurofibrosis in the process of chronic degeneration of nerve injury and the effects of motor neurons (MNs) transplantation on neurofibrosis and repair of nerve injury were studied by transcriptome sequencing and bioinformatics analysis, which were confirmed by in vivo and in vitro experiments. Even 3 months after nerve injury, the distal nerve maintained high levels of transforming growth factor ß-1 (TGFß-1) and Snail family transcriptional repressor 2 (Snai2). The microenvironment TGFß-1, Snai2 and endogenous TGFß-1 formed a positive feedback loop in vivo and in vitro, which may contribute to the sustained EMT state and neurofibrogenesis in the distal injured nerve. Inhibiting TGFß-1 and Snai2 expression and reversing EMT can be achieved by transferring MNs to distal nerves, and the removal of transplanted MNs is capable of reactivating EMT and promoting the growth of proximal axons. In conclusion, EMT persisting can be an explanation for distal neurofibrosis and a potential therapeutic target. By reversibly regulating EMT, MNs transplantation can alleviate neurofibrogenesis of distal nerve in chronic degeneration.

Safflor yellow treating angina pectoris: A pharmacoeconomic evaluation and network meta-analysis.

BACKGROUND: Coronary heart disease (CHD) is a cardiovascular disease caused by myocardial ischemia. In China, safflor yellow and artemisinin-based combination therapies have been extensively used to treat angina pectoris. METHODS: Efficacies were provided by a network meta-analysis following the PRISMA 2020 checklist. Cost-effectiveness analysis was based on patient perspectives. Two-way and probabilistic sensitivity analyses were conducted to assess the robustness of the study results. RESULTS: Conventional treatment combined with safflower is a better choice against angina pectoris. Sensitivity analysis showed that the model was sensitive to the treatment efficacy rather than the drug cost. CONCLUSION: Conventional treatment combined with safflower injection is suggested to treat angina pectoris. Low molecular weight heparin or compound Danshen-dropping pills can be used to increase the recovery rate of angina pectoris, according to conventional treatment combined with safflower injection.

The Consistency Between the Chinese Essential Medicines List and Treatment Guidelines-Taking Oncology Medicines as an Example.

The concepts of "essential medicine" and "national medicine policy" were first put forward for the first time at the World Health Assembly in 1975 in an effort to alleviate the problem of medicine unavailability in developing and poor countries. The essential medicine system in China has experienced three development stages since 1979, when the concept of essential medicines was first introduced, to actively respond to the call of the World Health Organization. Currently, the essential medicines list published in China is the national essential medicines list (2018 Edition). In this study, we examined the consistency between the essential medicines for treating seven cancers (liver cancer, breast cancer, esophageal cancer, lung cancer, colorectal cancer, gastric cancer, and leukemia) and the recommended medicines by cancer treatment guidelines to determine whether the essential medicines are of high quality for clinical needs. The results indicated that the degree of similarity between oncology medicines on the essential medicines list and oncology medicines recommended by guidelines was low, with the majority falling between 30 and 60%. Therefore, to improve the quality of essential medicines, it is necessary to further improve the matching degree. In addition, to further improve the consistency between the essential medicines list and treatment guidelines, the following suggestions are put forward in this paper: (1). Formulate universal treatment guidelines; (2). When selecting essential medicines, greater consideration should be given to those recommended in the guidelines; (3). The essential medicines list and treatment guidelines should be concurrently updated; (4). The cycle for updating the essential medicines list and treatment guidelines should be shortened.