Study on the therapeutic mechanism of HJ granules in a rat model of urinary tract infection caused by Escherichia coli.

ETHNOPHARMACOLOGICAL RELEVANCE: Urinary tract infections (UTIs) are globally prevalent infectious diseases, predominantly caused by uropathogenic Escherichia coli (UPEC). The misuse of antibiotics has led to the emergence of several drug-resistant strains. Traditional Chinese Medicine (TCM) has its own advantages in the treatment of UTIs. HJ granules is a herbal formula used for the treatment of UTIs. However, its mechanism of action is not clear. AIM OF THE STUDY: The aim of this study was to investigate the therapeutic efficacy and mechanism of action of HJ granules in a rat model of UTI caused by Escherichia coli (E coli) CFT073. MATERIALS AND METHODS: SD rats were selected to establish a rat UTI model by injecting UPEC strain CFT073 into the bladder using the transurethral placement method. HJ granules were administered to rats after modelling and the efficacy of HJ granule was investigated by measuring urinary decanalogue, inflammatory factors in bladder tissue and pathological changes in the bladder after 3d of administration. Expression of sonic hedgehog (SHH), NOD-like receptor thermoprotein domain 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and activation of cysteinyl aspartate specific proteinase-1 (caspase-1) were detected by western blotting and immunofluorescence staining in rat bladder tissue. NLRP3, ASC and caspase-1, a cysteine-containing aspartic protein, were expressed and activated. RESULTS: The results showed that infection of rats with UPEC resulted in increased pH and erythrocytes in bladder irrigation fluid; increased expression of IL-1ß, IL-6 and SHH and decreased expression of IL-10 in bladder tissue; and significant upregulation of the expression of both SHH and NLRP3 inflammasom and significant activation of NLRP3 inflammasom. HJ granules significantly increased the concentration of IL-10 in the bladder, inhibited the expression of SHH and NLRP3 inflammasom in bladder tissue, and suppressed the activation of NLRP3 inflammasom, thereby reducing inflammatory lesions in bladder tissue. CONCLUSION: HJ granules may improve bladder injury and treat UTIs by inhibiting the expression and activation of NLRP3 inflammasom.

Zhisou powder suppresses airway inflammation in LPS and CS-induced post-infectious cough model mice via TRPA1/TRPV1 channels.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhisou Powder (ZSP), a traditional Chinese medicine (TCM) prescription, has been widely used in the clinic for the treatment of post-infectious cough (PIC). However, the exact mechanism is not clear. AIM OF THE STUDY: The aim of this study was to investigate the ameliorative effect of ZSP on PIC in mice. The possible mechanisms of action were screened based on network pharmacology, and the potential mechanisms were explored through molecular docking and in vivo experimental validation. MATERIALS AND METHODS: Lipopolysaccharide (LPS) (80µg/50 µL) was used to induce PIC in mice, followed by daily exposure to cigarette smoke (CS) for 30 min for 30 d to establish PIC model. The effects of ZSP on PIC mice were observed by detecting the number of coughs and cough latency, peripheral blood and bronchoalveolar lavage fluid (BALF) inflammatory cell counts, enzyme-linked immunosorbent assay (ELISA), and histological analysis. The core targets and key pathways of ZSP on PIC were analyzed using network pharmacology, and TRPA1 and TRPV1 were validated using RT-qPCR and western blotting assays. RESULTS: ZSP effectively reduced the number of coughs and prolonged the cough latency in PIC mice. Airway inflammation was alleviated by reducing the expression levels of the inflammatory mediators TNF-α and IL-1ß. ZSP modulated the expression of Substance P, Calcitonin gene-related peptide (CGRP), and nerve growth factor (NGF) in BALF. Based on the results of network pharmacology, the mechanism of action of ZSP may exert anti-neurogenic airway-derived inflammation by regulating the expression of TRPA1 and TRPV1 through the natural active ingredients α-spinastero, shionone and didehydrotuberostemonine. CONCLUSION: ZSP exerts anti-airway inflammatory effects through inhibition of TRPA1/TRPV1 channels regulating neuropeptides to alleviate cough hypersensitivity and has a favorable therapeutic effect on PIC model mice. It provides theoretical evidence for the clinical application of ZSP.

Two undescribed benzopyran derivatives from Ranunculus sceleratus L. with their in vitro anti-inflammatory activity in lipopolysaccharide-activated RAW 264.7 cells.

Previous studies on Ranunculus sceleratus L. have shown the existence of coumarins and their anti-inflammatory effect. Phytochemical work was conducted to investigate the bioactive compounds, leading to the isolation of two undescribed benzopyran derivatives, namely ranunsceleroside A (1) and B (3), together with two known coumarins (2, 4) from the whole plant of R. sceleratus L. All compounds were structurally identified by extensive spectroscopic analysis and then investigated for their inhibitory effect on nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) production induced by lipopolysaccharide (LPS) in RAW 264.7 murine macrophages, repectively. As a result, compound 1-4 presented inhibitory effects on the production of NO, TNF-α, IL-1ß, and IL-6 in a concentration-dependent manner, which provides a potential chemical basis for the traditional use of R. sceleratus L. as an anti-inflammatory plant.

L-arginine metabolism inhibits arthritis and inflammatory bone loss.

OBJECTIVES: To investigate the effect of the L-arginine metabolism on arthritis and inflammation-mediated bone loss. METHODS: L-arginine was applied to three arthritis models (collagen-induced arthritis, serum-induced arthritis and human TNF transgenic mice). Inflammation was assessed clinically and histologically, while bone changes were quantified by µCT and histomorphometry. In vitro, effects of L-arginine on osteoclast differentiation were analysed by RNA-seq and mass spectrometry (MS). Seahorse, Single Cell ENergetIc metabolism by profilIng Translation inHibition and transmission electron microscopy were used for detecting metabolic changes in osteoclasts. Moreover, arginine-associated metabolites were measured in the serum of rheumatoid arthritis (RA) and pre-RA patients. RESULTS: L-arginine inhibited arthritis and bone loss in all three models and directly blocked TNFα-induced murine and human osteoclastogenesis. RNA-seq and MS analyses indicated that L-arginine switched glycolysis to oxidative phosphorylation in inflammatory osteoclasts leading to increased ATP production, purine metabolism and elevated inosine and hypoxanthine levels. Adenosine deaminase inhibitors blocking inosine and hypoxanthine production abolished the inhibition of L-arginine on osteoclastogenesis in vitro and in vivo. Altered arginine levels were also found in RA and pre-RA patients. CONCLUSION: Our study demonstrated that L-arginine ameliorates arthritis and bone erosion through metabolic reprogramming and perturbation of purine metabolism in osteoclasts.

Immobilization of cadmium in river sediments by different modified nanoscale zero-valent iron: performance, mechanisms, and Fe dissolution.

Modified nanoscale zero-valent iron (NZVI) exhibited great potential for the remediation of heavy metal contaminated river sediments, but its mechanisms and environmental risks are still unclear. This study systematically discussed the performance and the mechanisms of modified NZVI materials, i.e., sodium alginate-coated NZVI (SNZVI), rhamnolipid-coated NZVI (RNZVI), and graphene oxide-loaded NZVI (GNZVI), for the stabilization of Cd in sediment, with the exploration of their stability to Cd at various pH values and Fe dissolution rate. Compared with the control, the toxicity characteristic leaching procedure (TCLP) leachable Cd decreased by 52.66-96.28%, and the physiologically based extraction test (PBET) extractable Cd decreased by 44.68-70.21% after 56 days of incubation with the immobilization efficiency varying according to GNZVI > RNZVI > SNZVI > NZVI. Besides, the adsorption behavior of Cd on materials was fitted with the Freundlich model and classified as an endothermic, spontaneous, and chemical adsorption process. SEM-EDX, XRD, and FTIR results verified that the stabilization mechanisms of Cd were principally based on the adsorption, complexation of Cd2+ with secondary Fe minerals (including Fe2O3, γ-Fe2O3, and γ-FeOOH) and precipitation (Cd(OH)2). From the risk assessment results, it was observed that the materials were favorable for Cd stabilization at a pH range from 7 to 11, meanwhile, the leaching concentration of Fe in the overlying water was detected below the limit value. These findings pave the way to developing an effective strategy to remediate Cd contaminated river sediments.

The efficacy of Fuke Qianjin tablets combined with clomiphene citrate on infertility patients with polycystic ovary syndrome: A retrospective analysis.

PURPOSE: Clinical efficacy of Fuke Qianjin tablets combined with clomiphene citrate on infertility patients with polycystic ovary syndrome (PCOS) was expected to be retrospectively analyzed in this study. METHODS: In this paper, 100 infertility patients with PCOS were selected and divided into the observation and control groups based on different medications. Firstly, clinical data of both groups of patients were acquired. Then, the uterine receptivity and ovarian status, the levels of sex hormones, inflammation and oxidative stress, and the pregnancy outcomes between the 2 groups were compared and analyzed before and after treatment. RESULTS: After a variety of comparisons and analyses, Fuke Qianjin tablets combined with clomiphene citrate were confirmed to improve the uterine receptivity and ovarian status, levels of sex hormone, inflammation and oxidative stress, and pregnancy outcomes in infertility patients with PCOS. CONCLUSIONS: Overall, Fuke Qianjin tablets + clomiphene citrate treatment shows good clinical efficacy and is worth promotion in clinical practice.

Intercropping of kenaf and soybean affects plant growth, antioxidant capacity, and uptake of cadmium and lead in contaminated mining soil.

Intercropping is considered a sustainable agricultural practice that can reduce the environmental impacts on agriculture. Our study investigated the morphology, physiology, and cadmium (Cd) and lead (Pb) uptake of kenaf (Hibiscus cannabinus L.) and soybean (Glycine max L.) under intercropping in mining soil. Results showed that mutual intercropping is conducive to the growth and biomass accumulation of kenaf and soybean, compared to their respective monoculture. Intercropping increased the relative chlorophyll index in kenaf, while that in soybean had no significant effect. Furthermore, intercropping increased the antioxidant enzyme activity of kenaf, while that of soybean reduced or had no significant effect. The content of malondialdehyde (MDA) was decreased in both of the species. Compared to their respective monoculture, Cd content was increased in kenaf leaves and reduced in soybean roots. Moreover, intercropping decreased the Pb content in tissues of both the species, except that Pb content of kenaf roots was increased. At the same time, root, leaf, or stem bioconcentration factors also performed the same trend, and TF was less than 1. These results indicated that intercropping can increase the plant growth and decrease the metal content in plant tissues. Present findings could provide support for future research on kenaf and soybean cultivation in contaminated lands. In addition, the present study strengthens our understanding about the effectiveness of intercropping system on heavy metal-contaminated lands for sustainable agricultural production.

Application value of tumor necrosis factor inhibitors in in vitro fertilization-embryo transfer in infertile women with polycystic ovary syndrome.

BACKGROUND: Clinical value of tumor necrosis factor (TNF) inhibitors in in vitro fertilization-embryo transfer (IVF-ET) in infertile women with polycystic ovary syndrome (PCOS) was investigated in this study. METHODS: A retrospective analysis was performed on the clinical data of 100 PCOS patients who received IVF-ET for the first time at Hebei Institute of reproductive health science and technology from January 2010 to June 2020. The patients were divided into Inhibitor group and Control group according to whether they were treated with or without TNF inhibitors. Next, the two groups were subject to comparison in terms of the days of gonadotropin (Gn) use, total dosage of Gn, trigger time, hormone level and endometrial condition on the day of human chorionic gonadotropin (HCG) injection, the effects of two different regimens on controlled ovarian hyperstimulation (COH) and pregnancy outcomes. RESULTS: There were no significant differences in baseline characteristics between the two groups, including age, duration of infertility, body mass index (BMI), ovarian volume, antral follicle count, and basal hormone levels. Compared with the Control group, the days of Gn use and trigger time of patients in the Inhibitor group were significantly shortened, and the total Gn dosage was notably reduced. In terms of sex hormone levels on the HCG injection, the Inhibitor group displayed much lower serum estradiol levels while higher serum luteinizing hormone and progesterone (P) levels than the Control group. Notably, the high-quality embryo rate was also significantly increased with the use of TNF inhibitors. However, significant differences were not observed in endometrial thickness (on the day of HCG injection), proportion of endometrial A, B and C morphology (on the day of HCG injection), cycle cancellation rate, number of oocytes retrieved, fertilization rate, and cleavage rate between the two groups. Importantly, the clinical pregnancy rate in the Inhibitor group was significantly higher than that in the Control group, but there was no significant difference in the biochemical pregnancy rate, early abortion rate, multiple birth rate, ectopic pregnancy rate and number of live births between the two groups. CONCLUSION: Collectively, after application of TNF-α inhibitor regimen, superior overall treatment effect can be observed in infertile PCOS patients receiving IVF-ET. Therefore, TNF inhibitors have certain application value in IVF-ET in infertile women with PCOS.

Spatio-temporal variation of soil microplastics as emerging pollutant after long-term application of plastic mulching and organic compost in apple orchards.

Microplastics (MPs) pollution in agroecosystems have aroused great alarm and widespread concern. However, the spatial distribution and temporal variation characteristics of MPs in apple orchards with long-term plastic mulching and organic compost input are still poorly understood. This study investigated MPs accumulation characteristics and vertical distribution after applying plastic mulch and organic compost in apple orchards for 3 (AO-3), 9 (AO-9), 17 (AO-17), and 26 (AO-26) years on the Loess Plateau. The clear tillage (no plastic mulching and organic composts) area was used as a control (CK). At a soil depth of 0-40 cm, AO-3, AO-9, AO-17, and AO-26 treatments increased the abundances of MPs, and the black fibers and fragments of rayon and polypropylene were dominant. In the 0-20 cm soil layer, the abundances of MPs increased with the treatment time; the abundance was 4333 pieces kg-1 after 26 years of treatment, gradually decreasing with soil depth. In different treatments and soil layers, the percentages of MPs <1000 µm were dominant (>50%). The AO-17 and AO-26 treatments significantly increased the MPs with the size of 0-500 µm at 0-40 cm and the abundances of pellets in 0-60 cm soil. In conclusion, the long-term (≥17 years) application of plastic mulching and organic composts increased the abundances of small particles at 0-40 cm, and plastic mulching contributed the most to MPs, while organic composts increased the complexity and diversity of MPs.

Physiological and DNA methylation analysis provides epigenetic insights into kenaf cadmium tolerance heterosis.

Soil heavy metal pollution is one of the most challenging problems. Kenaf is an important natural fiber crop with strong heterosis and a higher tolerance to heavy metals. However, little is known about the molecular mechanisms of kenaf heavy metal tolerance, especially the mechanism of genomic DNA methylation regulating heterosis. In this study, kenaf cultivars CP085, CP089, and their hybrid F1 seedlings were subjected to 300 µM cadmium stress and found obvious heterosis of cadmium resistance in morphology and antioxidant enzyme activity of F1 hybrid seedlings. Through methylation-sensitive amplification polymorphism (MSAP) analysis, we highlighted that the total DNA methylation level under cadmium decreased by 16.9 % in F1 and increased by 14.0 % and 3.0 % in parents CP085 and CP089, respectively. The hypomethylation rate was highest (21.84 %), but hypermethylation was lowest (17.24 %) in F1 compared to parent cultivars. In particular, principal coordinates analysis (PCoA) indicates a significant epigenetic differentiation between F1 and its parents under cadmium. Furthermore, 21 differentially methylated DNA fragments (DMFs) were analyzed. Especially, the expression of NPF2.7, NADP-ME, NAC71, TPP-D, LRR-RLKs, and DHX51 genes were changed due to cadmium stress and related to cytosine methylation regulation. Finally, the knocked-down of the differentially methylated gene NPF2.7 by virus-induced gene silencing (VIGS) resulted in increased sensitivity of kenaf seedlings under cadmium stress. It is speculated that low DNA methylation levels can regulate gene expression that led to the heterosis of cadmium tolerance in kenaf.

Comprehensive analysis reveals the underlying mechanism of arbuscular mycorrhizal fungi in kenaf cadmium stress alleviation.

Soil Cadmium (Cd) contamination has become a severe environmental problem around the world. Kenaf has great potential for utilization and phytoremediation of soil contaminated with heavy metal. Arbuscular mycorrhizal fungi (AMF) can help plants alleviate Cd stress, but the underlying mechanism remains completely unknown. In this study, kenaf was inoculated or not inoculated with AMF at cadmium concentrations of 10 mg kg-1 and 50 mg kg-1 from the seedling stage to the vigorous growth stage. The results showed that AMF symbionts improved nutrient transport efficiency and significantly improved plant growth. Additionally, AMF colonization increased cell wall polysaccharide content which help to bind Cd in the cell wall and reduced the transport of Cd to aboveground plant tissues. The increase in soil pH (6.9), total balcomycin and easily extractable balcomycin content facilitated the chelation of metal by mycorrhizal fungi and reduced the biological effectiveness of Cd. Furthermore, AMF upregulated the expression levels of key kenaf genes, such as Hc.GH3.1, Hc.AKR, and Hc.PHR1, which plays an important role in enhancing kenaf Cd tolerance. Our findings systematically revealed the mechanisms by which AMF responds to Cd stress in kenaf, inoculation of AMF with kenaf could be used to enhance the removal of Cd from soil pollution in mining areas by phytoremediation.

First-line treatments for advanced hepatocellular carcinoma: a network meta-analysis and cost-effectiveness analysis in China and the United States.

Background: Various therapeutic strategies are available for the first-line treatment of patients with advanced hepatocellular carcinoma (aHCC). But which approach is the most cost-effective remains uncertain. Objectives: This study aims to evaluate the cost-effectiveness of first-line strategies in aHCC patients from the perspective of Chinese and US payers. Design: A network meta-analysis (NMA) and cost-effectiveness study. Data sources and methods: A NMA was conducted to collect all first-line strategies with aHCC from 1 October 1 2018 until 1 January 2022. The relevant randomized controlled trial literature in PubMed, Embase, and Cochrane Library for the last 3 years were searched. The abstracts of meetings of the American Society of Clinical Oncology, European Society of Medical Oncology, and American Association for Cancer Research were also reviewed. A Markov model that included three states was developed. One-way sensitivity and probabilistic sensitivity analysis were performed to investigate the uncertainty of the economic evaluation. Scenario analysis was conducted to explore the economic benefits of treatment strategies in low-income populations. Results: Base-case analysis in China included 1712 patients showed that atezolizumab combined with bevacizumab, sintilimab combined with bevacizumab, lenvatinib (LEVA), and sorafenib (SORA) added 0.46, 1.25, 0.77, and -1.08 quality-adjusted life-years (QALYs), respectively, compared with donafenib, resulting in an incremental cost-effective ratio of $85607.88, $12109.27, and $1651.47 per QALY at a willingness-to-pay (WTP) of $11101.70/QALY. In the United States, only the incremental cost-effectiveness ratios (ICERs) of SORA was higher that were lower than the WTP threshold ($69375/QALY), and LEVA was the most cost-effective strategy with the ICERs were 25022.13/QALY. Conclusion: The NMA and cost-effectiveness analysis revealed that LEVA is the favorite choice in the first-line treatment of Chinese aHCC patients and US payers' perspective when the WTP was $11101.70/QALY in China and $69375.0/QALY in the United States. Registration: This study has been registered on the PROSPERO database with the registration number CRD42021286575.

[Spatial characteristics and source apportionment of urban environmental black carbon concentrations based on mobile monitoring]. / 基于移动监测的城市环境大气黑碳浓度空间特征及来源解析.

Black carbon (BC) is an important component of airborne fine particulate matter, with significant impacts on global climate change and human health. Taking Minhang District of Shanghai as the study area, a microaethalometer (MA200) and GPS were installed on the electric taxi to form a mobile observation platform to identify the spatial distribution and hot spots of atmospheric BC in urban environment. We analyzed the sources and influencing factors of BC. The results showed that the overall characteristics of the spatial distribution pattern of near surface atmospheric BC in Minhang District of Shanghai were high in the north and low in the south. The average BC concentration was (4.11±4.87) µg·m-3. The average concentrations of BC in working days and non-working days were (4.22±1.49) and (3.52±2.26) µg·m-3. The variability of BC concentration in the high value area was large, indicating that the increases of BC concentration in mobile observation were related to traffic accidents in the road section. In addition to human activities, large-scale dense vegetation might inhibit BC diffusion. The Absorption ngström Exponent (AAE) was (0.82±0.54), which was closer to that of fossil fuel combustion. The contributions of fossil fuel emissions, biomass combustion, and mixed sources to BC sources were 67.5%, 4.9% and 27.6%, respectively.

Distinct Metabolism of Bone Marrow Adipocytes and their Role in Bone Metastasis.

Bone marrow adipocytes (BMAs) represent 10% of the total fat mass of the human body and serve as an energy reservoir for the skeletal niche. They function as an endocrine organ by actively secreting fatty acids, cytokines, and adipokines. The volume of BMAs increases along with age, osteoporosis and/or obesity. With the rapid development of multi-omic analysis and the advance in in vivo imaging technology, further distinct characteristics and functions of BMAs have been revealed. There is accumulating evidence that BMAs are metabolically, biologically and functionally unique from white, brown, beige and pink adipocytes. Bone metastatic disease is an uncurable complication in cancer patients, where primary cancer cells spread from their original site into the bone marrow. Recent publications have highlighted those BMAs could also serve as a rich lipid source of fatty acids that can be utilized by the cancer cells during bone metastasis, particularly for breast, prostate, lung, ovarian and pancreatic cancer as well as melanoma. In this review, we summarize the novel progressions in BMAs metabolism, especially with multi-omic analysis and in vivo imaging technology. We also update the metabolic role of BMAs in bone metastasis, and their potential new avenues for diagnosis and therapies against metastatic cancers.

Targeting PI3K/AKT/mTOR pathway to enhance the anti-leukemia efficacy of venetoclax.

BACKGROUND: The treatment of acute myeloid leukemia (AML) is developing towards "targeted therapy", which faces challenges such as low sensitivity and drug resistance. Therefore, targeted drugs need to be used in combination with other drugs to overcome clinical problems. OBJECTIVE: AML cells and animal models were used to determine the synergistic anti-leukemic effect of Dactolisib (BEZ235) and Venetoclax (ABT199) and explore its mechanism. METHODS: In vitro experiments, we used cell counting kit-8 (CCK8), flow cytometry, real-time quantitative PCR (qPCR), and Western blot to detect the anti-leukemic effects of ABT199 and BEZ235. In vivo experiments, female nude mice were injected subcutaneously with THP-1 cells to form tumors, evaluate the combined effect of ABT199 and BEZ235 by indicators such as tumor size, tumor weight, Ki67 and cleaved-Caspase3 staining. The mice's body weight and HE staining were used to evaluate the liver injury and adverse drug reactions. RESULTS: The combination of BEZ235 and ABT199 has a synergistic effect through promoting apoptosis and inhibiting proliferation. The BEZ235 increased the drug sensitivity of ABT199 by reducing the MCL-1 protein synthesis and promoted the degradation of MCL-1 protein, which is considered as the mechanism of reversing ABT199 resistance. Furthermore, the BEZ235 and ABT199 can synergistically enhance the inhibition of PI3K/AKT/mTOR pathway. CONCLUSION: The combination of BEZ235 and ABT199 exhibits a synergistic anti-tumor effect in AML by down-regulating MCL-1 protein.

High-Throughput and Untargeted Metabolic Profiling Revealed the Potential Effect and Mechanisms of Paeoniflorin in Young Asthmatic Rats.

Paeoniflorin (PF) is a multi-target monoterpenoid glycoside and possesses broad pharmacological functions, e.g., anti-inflammation, anti-depression, antitumor, abirritation, neuroprotection, antioxidant, and enhancing cognitive and learning ability. PF has gained a large amount of attention for its effect on asthma disease as the growth rate of asthma has increased in recent years. However, its mechanism of action on asthma is still unclear. In this study, we have explored the action mechanism of PF on asthma disease. Furthermore, high-throughput untargeted metabolic profiling was performed through ultraperformance liquid chromatography/electrospray ionization quadruple time-of-flight high-definition mass spectrometry (QA) UPLC-Q/TOF-MS combined with pattern recognition approaches and pathway analysis. A total of 20 potential biomarkers were discovered by UPLC/MS and urine metabolic profiling. The key pathways including the citrate cycle (the TCA cycle), pyrimidine metabolism, pentose phosphate pathway, tyrosine metabolism, and tryptophan metabolism were affected by PF. In conclusion, we have discovered metabolite biomarkers and revealed the therapeutic mechanism of PF based on liquid chromatography coupled with mass spectrometry untargeted metabolomics. The untargeted metabolomics combined with UPLC-MS is a useful tool for exploring the therapeutic mechanism and targets of PF in the treatment of asthma. Metabolomics combined with UPLC-MS is an integrated method to explore the metabolic mechanism of PF in the treatment of asthma rats and to reveal the potential targets, providing theoretical support for the study of the treatment of PF.

[Research on the clinical application of drainage tube after the operation of percutaneous endoscopic lumbar discectomy].

OBJECTIVE: To investigate the clinical significance and related factors of drainage tube after percutaneous endoscopic lumbar discectomy(PELD). METHODS: The clinical data of 151 patients with lumbar disc herniation who underwent PELD from January 2019 to September 2019 was retrospectively analyzed. According to whether the drainage tube was used after operation, the patients were divided into drainage tube group and non drainage tube group. The placement time and total drainage volume were recorded. The characteristics of patients, such as age, gender, body mass index, lumbar disc herniation segment, smoking history, basic diseases and whether taking anticoagulants, were analyzed by single factor and multiple factor. RESULTS: Drainage tubes were used in 32 patients after PELD. There were statistical differences in visual analogue scale(VAS) and Japanese Orthopaedic Assiciation(JOA) scores between postoperative and preoperative of that in two groups(P<0.05). There were statistical differences in VAS and JOA scores at discharge between two groups(P<0.05), while there were no statistical differences at other time points(P>0.05). Univariate analysis showed that age, basic diseases and whether taking anticoagulants were related to the use of drainage tube, but gender, body mass index, lumbar disc herniation segment and smoking history were not significantly related to the use of drainage tube. Multivariate analysis showed that elderly patients, complicated with hypertension and diabetes, taking anticoagulants were related to the use of drainage tube. CONCLUSION: The use of drainage tube after percutaneous endoscopic lumbar discectomy can improve the symptoms of lumbar and leg pain in early stage. For elderly patients with hypertension, diabetes and taking anticoagulants drugs, drainage tube can be considered after transforaminal endoscopy.

Circular RNA mmu_circ_0001295 from hypoxia pretreated adipose-derived mesenchymal stem cells (ADSCs) exosomes improves outcomes and inhibits sepsis-induced renal injury in a mouse model of sepsis.

Microvascular dysfunction causes mortality in the presence of sepsis and multi-organ failure. Previous studies have demonstrated that exogenous administration of exosomes from adipose-derived mesenchymal stem cells (ADSCs) protects against sepsis, improves organ function, decreases vascular leakage and increases survival. However, the underlying regulatory mechanism was largely unknown. Therefore, in this study, a mouse sepsis model based on cecal ligation and puncture (CLP) was constructed. Exosomes from various ADSCs were intravenously administered at 4 h post CLP. Treatment with ADSC exosomes (Exo), particularly those with hypoxic pretreatment (HExo), enhanced survival, suppressed renal vascular leakage and decreased kidney dysfunction in septic mice. HExo ameliorated sepsis-induced increases in chemokine and cytokine plasma levels. Furthermore, the HExo circRNA content, determined through next-generation sequencing, revealed abundant mmu_circ_0001295. Further studies demonstrated that downregulation of exosomal mmu_circ_0001295 suppressed the exosomes' protective effects against sepsis. HExo prevented microvascular dysfunction, thus potentially improving sepsis outcomes via mmu_circ_0001295 delivery. In summary, the data indicated that HExo elongate sepsis-induced renal injury through delivering mmu_circ_0001295.

Forkhead-box C1 attenuates high glucose-induced trophoblast cell injury during gestational diabetes mellitus via activating adenosine monophosphate-activated protein kinase through regulating fibroblast growth factor 19.

Gestational diabetes mellitus (GDM) is a complication developed during pregnancy and recover after childbirth. The purpose of this study was to investigate the protective role of FOXC1 during GDM and the underlying mechanism. FOXC1 was downregulated in GDM placental tissues and HG-treated HTR-8/SVneo cells. Overexpression of FOXC1 prevented HG-induced inhibition of cell proliferation, migration and invasion. FOXC1 suppressed HG-induced cell apoptosis in HTR-8/SVneo cells. The apoptosis-related proteins: cleaved caspase-3, cleaved caspase-9 and BAX, were also downregulated by FOXC1 overexpression. FOXC1 increased glucose uptake and improved insulin sensitivity. The expression of FOXC1 was positively correlated with FGF19 expression. FOXC1 regulated the expression of FGF19 and phosphorylation of AMPK. Inhibition of FGF19 attenuated the biological functions of FOXC1 through inactivation of AMPK. In conclusion, this study demonstrates that FOXC1 attenuates HG-induced trophoblast cell injury through upregulating FGF19 to activate the AMPK signaling pathway during GDM, suggesting that FOXC1 is a potential therapeutic target for drug discovery in the future.