Retrospective analysis of Advanced Heart Failure and/or Cardiogenic Shock in Patients with Aortic Valve Stenosis Treated by Transcatheter Aortic Valve Replacement and a Nomogram Model Construction.

Objective: Currently, there is little information about the risk of sudden cardiac death and its predictors in aortic valve stenosis patients after transcatheter aortic valve replacement (TAVR). Therefore, we conducted a large sample cohort study on TAVR patients to evaluate the predictive factors and incidence of heart failure death caused by advanced heart failure (AHF) and sudden cardiac death. Furthermore, a nomogram model to predict its risk was constructed. Methods: This study retrospectively analyzed the data of 241 consecutive participants who had received TAVR treatment for aortic valve stenosis in our hospital from January 2020 to January 2022. The characteristics of the subjects, including myocardial zymogram, renal function, biochemical parameters, and cardiac ultrasound parameters, were collected. Moreover, a nomogram was constructed to predict the risk of sudden cardiac death and its predictors in patients after transcatheter aortic valve replacement (TAVR). The model was validatedinternally using measures of calibration and decision curve analysis. Results: Six independent risk factors(Age, smoking, diabetes, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, and fasting blood glucose) were finally recruited into the nomogram model to predict the risk of advanced heart failure and/or cardiogenic shock in AS patients treated by TAVR. Besides, the decision curve analysis and receiver operating characteristic curve indicated that the nomogram prediction models showed positive clinical benefits. Conclusions: The Age, smoking, diabetes, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, and fasting blood glucose are the independent risk factors for advanced heart failure and/or cardiogenic shock in AS patients treated by TAVR. The construction of nomograms is beneficial in predicting the risk of advanced heart failure and/or cardiogenic shock in AS patients treated by TAVR.

Performance evaluation of rhamnolipid biosurfactant produced by Pseudomonas aeruginosa and its effect on marine oil-spill remediation.

This study aimed to reveal that the effect of biosurfactant on the dispersion and degradation of crude oil. Whole genome analysis showed that Pseudomonas aeruginosa GB-3 contained abundant genes involved in biosurfactant synthesis and metabolic processes and had the potential to degrade oil. The biosurfactant produced by strain GB-3 was screened by various methods. The results showed that the surface tension reduction activity was 28.6 mN·m-1 and emulsification stability was exhibited at different pH, salinity and temperature. The biosurfactant was identified as rhamnolipid by LC-MS and FTIR. The fermentation conditions of strain GB-3 were optimized by response surface methodology, finally the optimal system (carbon source: glucose, nitrogen source: ammonium sulfate, C/N ratio:16:1, pH: 7, temperature: 30-35 °C) was determined. Compared with the initial fermentation, the yield of biosurfactant increased by 4.4 times after optimization. In addition, rhamnolipid biosurfactant as a dispersant could make the dispersion of crude oil reach 38% within seven days, which enhanced the bioavailability of crude oil. As a biostimulant, it could also improve the activity of indigenous microorganism and increase the degradation rate of crude oil by 10-15%. This study suggested that rhamnolipid biosurfactant had application prospect in bioremediation of marine oil-spill.

Characteristic microbiome and synergistic mechanism by engineering agent MAB-1 to evaluate oil-contaminated soil biodegradation in different layer soil.

Bioremediation is a sustainable and pollution-free technology for crude oil-contaminated soil. However, most studies are limited to the remediation of shallow crude oil-contaminated soil, while ignoring the deeper soil. Here, a high-efficiency composite microbial agent MAB-1 was provided containing Bacillus (naphthalene and pyrene), Acinetobacter (cyclohexane), and Microbacterium (xylene) to be synergism degradation of crude oil components combined with other treatments. According to the crude oil degradation rate, the up-layer (63.64%), middle-layer (50.84%), and underlying-layer (54.21%) crude oil-contaminated soil are suitable for bioaugmentation (BA), biostimulation (BS), and biostimulation+bioventing (BS+BV), respectively. Combined with GC-MS and carbon number distribution analysis, under the optimal biotreatment, the degradation rates of 2-ring and 3-ring PAHs in layers soil were about 70% and 45%, respectively, and the medium and long-chain alkanes were reduced during the remediation. More importantly, the relative abundance of bacteria associated with crude oil degradation increased in each layer after the optimal treatment, such as Microbacterium (2.10-14%), Bacillus (2.56-12.1%), and Acinetobacter (0.95-12.15%) in the up-layer soil; Rhodococcus (1.5-6.9%) in the middle-layer soil; and Pseudomonas (3-5.4%) and Rhodococcus (1.3-13.2%) in the underlying-layer soil. Our evaluation results demonstrated that crude oil removal can be accelerated by adopting appropriate bioremediation approach for different depths of soil, providing a new perspective for the remediation of actual crude oil-contaminated sites.

Efficiency and equity of bed utilization in China's health institutions: based on the rank-sum ratio method.

OBJECTIVE: The study aimed to analyze the efficiency and equity of bed utilization in Please check if the section headings are assigned to appropriate levels.China's healthcare institutions and to compare and analyze the overall health resource utilization efficiency in recent years and some specific utilization conditions in 2021, to provide empirical experience for the allocation of health care resources in epidemic China. METHODS: To compare and analyze the overall health resource utilization efficiency of the whole country with that of the East, middle, and West in 2021, and to analyze the bed utilization efficiency of different types of healthcare institutions in China and the bed utilization efficiency of various types of specialist hospitals in the country in 2021 by using the rank-sum ratio method. RESULTS: In 2021, the bed utilization rate of China's health institutions was 69.82%, and the number of bed turnover times was 27.65 times; the bed utilization rate of hospitals was 74.6%, and the number of bed turnover times was 26.08 times. The number of hospital bed turnovers was highest in the western region, lowest in the central region, and close to the national average in the eastern region. The average length of stay for discharged patients was the highest in the central region, the lowest in the eastern region, and the same as the national average in the western region. The analysis of rank-sum ratio method shows that among different types of health institutions' bed utilization efficiency (r = 0.935, P = 0.000), general hospitals and traditional Chinese medicine hospitals have the best bed utilization rate, and the bed utilization rate of community health service centers (stations) needs to be improved; while among various types of specialized hospitals' bed utilization efficiency (r = 0.959, P = 0.000), oncology hospitals, thoracic hospitals, and hematology hospitals, children's hospitals have high bed utilization efficiency; leprosy hospitals, cosmetic hospitals, and stomatology hospitals have low bed utilization efficiency. Health technicians per 1,000 population are highest in the western region, lowest in the central region, and lower in the eastern region than in the western region but slightly higher than the national average. The number of beds in health institutions per 1,000 population is the highest in the central region, the lowest in the eastern region, and slightly lower in the northwest than in the central region but higher than the national average. CONCLUSION: China's investment in health funding in the field of health care has been on the rise in recent years. However, there still exists the situation of uneven investment in health expenses and inconsistent medical efficiency among regions. And change such a status quo can be further improved in terms of government, capital, human resources, technology, information system, and so on.

Efficacy and safety of gastrointestinal microbiome supplementation for allergic rhinitis: A systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Allergic rhinitis (AR) is a non-infective chronic inflammatory disease of nasal mucosa. PURPOSE: To evaluate the efficacy and safety of gastrointestinal microbiome supplementation (GMS) for patients with allergic rhinitis (AR), concerning improvement on symptoms and signs, laboratory outcomes, quality of life, and medication scores. METHODS: Five English databases were searched up to Dec 12th, 2022. Probiotics, prebiotics, and synbiotics were main therapies or adjuvants in experimental groups. Systematic reviews and meta-analyses were conducted based on the Cochrane systematic review method by using RevMan 5.4 Software, with meta-influence analyses, subgroup-analyses, meta-regression, and publication bias performed for exploration of heterogeneity by Stata V.14. Trial sequential analyses were performed by TSA 0.9, and quality of the results was accessed through the GRADE-pro GDT. RESULTS: Finally, extracted from 53 articles, 65 RCTs involving 3,634 participants with sound worldwide representativeness were included. Primary results showed better improvement in GMS groups on TNSS (WMD=1.05, P for WMD=0.004, 95%CI:0.34 to 1.76), overall nasal condition (WMD=1.25, P for WMD<0.001, 95%CI:0.90 to 1.61), overall quality of life (WMD=6.16, P for WMD<0.001, 95%CI:4.92 to 7.40) and medication score (WMD=0.42, P for WMD=0.42, 95%CI:-0.06 to 0.90).However, GMS groups were inferior than the controls concerning reduction on serum total IgE (WMD=-1.81) and ratios of serum Th1/Th2 (WMD=-1.06). Meta-regressions suggested significant (p<0.05) variations of the effects in some comparisons. In addition, results of sub-group analyses firstly revealed potential influence between final results and the variables above. Instantly after intervention, the GRADE levels of evidence were sound, including "High ⨁⨁⨁⨁" in 10, "Moderate ⨁⨁⨁◯" in 33, and "Low ⨁⨁◯◯" in nine comparisons. However, overall certainties decreased obviously during follow-ups. CONCLUSION: Overall, our pooled results firstly revealed that GMS yielded acceptable benefits for patients with AR compared with controls with sound certainties, after balancing the benefits and harms.

Prediction From Minimal Experience: How People Predict the Duration of an Ongoing Epidemic.

People are known for good predictions in domains they have rich experience with, such as everyday statistics and intuitive physics. But how well can they predict for problems they lack experience with, such as the duration of an ongoing epidemic caused by a new virus? Amid the first wave of COVID-19 in China, we conducted an online diary study, asking each of over 400 participants to predict the remaining duration of the epidemic, once per day for 14 days. Participants' predictions reflected a reasonable use of publicly available information but were meanwhile biased, subject to the influence of negative affect and future time perspectives. Computational modeling revealed that participants neither relied on prior distributions of epidemic durations as in inferring everyday statistics, nor on mechanistic simulations of epidemic dynamics as in computing intuitive physics. Instead, with minimal experience, participants' predictions were best explained by similarity-based generalization of the temporal pattern of epidemic statistics. In two control experiments, we further confirmed that such cognitive algorithm is not specific to the epidemic scenario and that minimal and rich experience do lead to different prediction behaviors for the same observations. We conclude that people generalize patterns in recent history to predict the future under minimal experience.

Prussian Blue Analogues with Optimized Crystal Plane Orientation and Low Crystal Defects toward 450†Wh kg-1 Alkali-Ion Batteries.

Prussian blue analogues (PBAs) have been regarded as promising cathode materials for alkali-ion batteries owing to their high theoretical energy density and low cost. However, the high water and vacancy content of PBAs lower their energy density and bring safety issues, impeding their large-scale application. Herein, a facile "potassium-ions assisted" strategy is proposed to synthesize highly crystallized PBAs. By manipulating the dominant crystal plane and suppressing vacancies, the as-prepared PBAs exhibit increased redox potential resulting in high energy density up to ≈450 Wh kg-1 , which is at the same level of the well-known LiFePO4 cathodes for lithium-ion batteries. Remarkably, unconventional highly-reversible phase evolution and redox-active pairs were identified by multiple in situ techniques for the first time. The preferred guest-ion storage sites and migration mechanism were systematically analysed through theoretical calculations. We believe these results could inspire the design of safe with high energy density.

Musical training alters neural processing of tones and vowels in classic Chinese poems.

Long-term rigorous musical training promotes various aspects of spoken language processing. However, it is unclear whether musical training provides an advantage in recognizing segmental and suprasegmental information of spoken language. We used vowel and tone violations in spoken unfamiliar seven-character quatrains and a rhyming judgment task to investigate the effects of musical training on tone and vowel processing by recording ERPs. Compared with non-musicians, musicians were more accurate and responded faster to incorrect than correct tones. Musicians showed larger P2 components in their ERPs than non-musicians during both tone and vowel processing, revealing increased focused attention on sounds. Both groups showed enhanced N400 and LPC for incorrect vowels (vs. correct vowels) but non-musicians showed an additional P2 effect for vowel violations. Moreover, both groups showed enhanced LPC for incorrect tones (vs. correct tones) but only non-musicians showed an additional N400 effect for tone violations. These results indicate that vowel/tone processing is less effortful for musicians (vs. non-musicians). Our study suggests that long-term musical training facilitates speech tone and vowel processing in a tonal language environment by increasing the attentional focus on speech and reducing demands for detecting incorrect vowels and integration costs for tone changes.

[Study on protective effect of Chaihu Shugan Powder against liver injury in rats with intrahepatic cholestasis by regulating FXR/Nrf2/ARE pathway].

This study aims to investigate the effect of Chaihu Shugan Powder(CHSG) on liver injury in rats with intrahepatic cholestasis by regulating farnesoid X receptor(FXR)/nuclear factor erythroid-2-related factor(Nrf2)/antioxidant response element(ARE) pathway. Eighty-four SD rats were classified into normal group, model group, CHSG-L group(0.5 g·kg~(-1)), CHSG-H group(2.5 g·kg~(-1)), ursodeoxycholic acid group(UDCA group, 100 mg·kg~(-1)), CHSG-H+sh-NC group(2.5 g·kg~(-1) CHSG+subcutaneous injection of sh-NC lentivirus), CHSG-H+sh-FXR group(2.5 g·kg~(-1) CHSG+subcutaneous injection of sh-FXR lentivirus), with 12 rats in each group. Rats were treated with corresponding drugs except for the normal group and the model group, once a day, for 7 days. On 5 th day, rats, except the normal group, were given α-naphthalene isothiocyanate(ANIT) at a dose of 100 mg·kg~(-1), once a day for 3 days to induce intrahepatic cholestasis, and the normal group was given the same amount of normal saline. Rats were anesthetized 1 h after the last administration and the 2 h bile flow was measured. Aeroset chemistry analyzer was employed to detect the levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(TBIL), and total bile acid(TBA) in rat serum. Based on hematoxylin and eosin(HE) staining, the pathological changes of rat liver tissue were observed. Glutathione peroxidase(GSH-Px), superoxide dismutase(SOD), and malondialdehyde(MDA) in rat liver tissue homogenate were monitored with corresponding kits. Western blot was used to detect the expression of FXR, Nrf2, and heme oxygenase-1(HO-1) proteins in rat liver tissue. Compared with the normal group, the model group showed many spots or concentrated necrotic areas in the liver tissue, infiltration of a large number of inflammatory cells, swelling liver cells with nuclear shrinkage. The 2 h bile flow, levels of GSH-Px and SOD, and relative expression of FXR, Nrf2, and HO-1 proteins were significantly lower, and the levels of ALT, AST, TBIL, TBA and MDA were significantly higher in the model group than in the normal group. Compared with the model group, CHSG-L group, CHSG-H group, and UDCA group demonstrated significant alleviation of pathological damage of the liver tissue, significantly high 2 h bile flow, levels of GSH-Px and SOD, and expression of FXR, Nrf2 and HO-1 proteins, and significantly low levels of ALT, AST, TBIL, TBA and MDA. Compared with the CHSG-H group, the CHSG-H+sh-FXR group had worse liver pathological damage, significantly low levels of 2 h bile flow, levels of GSH-Px and SOD, and expression of FXR, Nrf2, and HO-1 proteins, and significantly high levels of ALT, AST, TBIL, TBA, and MDA. CHSG may protect against liver injury in rats with intrahepatic cholestasis by activating the FXR/Nrf2/ARE pathway.

[Sesquiterpenoids from Aquilariae Lignum Resinatum].

Eight sesquiterpenoids were isolated from petroleum ether extract of Aquilariae Lignum Resinatum by various column chromatography techniques including silica gel, ODS, and semi-preparative HPLC. Their structures were identified on the basis of physicochemical properties, UV, IR, MS, and NMR spectroscopic data as(4S,5S,7R,10S)-5,7-dihydroxy-11-en-eudesmane(1),(7R,10S)-eudesma-4-en-11,15-diol(2),(2R,4S,5R,7R)-2-hydroxyeremophila-9,11-dien-8-one(3), 7α-H-9(10)-ene-11,12-epoxy-8-oxoeremophilane(4),(+)-9ß,10ß-epoxyeremophila-11(13)-en(5), 4(14)-eudesmene-8α,11-diol(6), 12,15-dioxo-selina-4,11-dien(7), and 2ß,8 aα-dihydroxy-11-en-eremophilane(8). Compounds 1 and 2 are new compounds, and their absolute configurations were determined by calculating ECD. Compounds 1, 4, and 6-8 could significantly improve taurocholic acid(TCA)-induced gastric mucosal GES-1 cell injury at a concentration of 20 µmol·L~(-1), and the cell protection rates were 23.51%±2.79%, 16.10%±1.25%, 24.45%±4.89%, 17.48%±2.93%, and 21.44%±2.39%, respectively.

Chrysophanol, a main anthraquinone from Rheum palmatum L. (rhubarb), protects against renal fibrosis by suppressing NKD2/NF-κB pathway.

PURPOSE: Chronic kidney disease (CKD), characterized as renal dysfunction and multi-system damage, has become a serious public health problem with high prevalence and mortality. Rheum palmatum L. (rhubarb) is one of the most widely used Chinese herb with renal protective activity. However, the active components and underlying mechanisms of rhubarb remain unknown. In this work, we tried to explore the pharmacological mechanism of chrysophanol, a main anthraquinone from rhubarb, against CKD by in vivo and in vitro models. STUDY DESIGN: The therapeutic effect of chrysophanol and its underlying mechanism were investigated using CKD mouse model induced by unilateral ureteral occlusion (UUO), and human kidney 2 (HK-2) cells stimulated by TGF-ß1 in vivo. METHODS: The impact of chrysophanol on renal function, inflammation, fibrosis of CKD mice were evaluated. Then, the protein expressions of FN1, collagen ɑI, α-SMA, NF-κB and naked keratinocyte homolog 2 (NKD2) were investigated. In vitro studies, the inhibition on inflammation and fibrogenesis by chrysophanol was further validated in TGF-ß1-stimulated HK2 cells, and the regulation of chrysophanol on NKD2/NF-κB pathway was analyzed. Moreover, NKD2 was overexpressed in HK-2 cells to confirm the role of NKD2/NF-κB pathway in chrysophanol-mediated efficacy. Finally, the binding mode of chrysophanol with NKD2 was studied using in silico molecular docking and microscale thermophoresis (MST) assay. RESULTS: Chrysophanol could significantly improve the kidney dysfunction, alleviate renal pathology, and reverse the elevated levels of renal fibrosis markers such as FN1, collagen ɑI and α-SMA. Furthermore, chrysophanol effectively inhibited TNF-α, IL-6, and IL-1ß production, and suppressed NF-κB activation and NKD2 expression. The findings of in vitro study were consistent with those of animal expriment. Using NKD2-overexpressing HK-2 cells, we also demonstrated that overexpression of NKD2 significantly compromised the anti-fibrotic effects of chrysophanol. In addition, molecular docking and MST analysis revealed that NKD2 was a direct target of chrysophanol. CONCLUSION: Together, our work demonstrated for the first time that chrysophanol could effectively ameliorate renal fibrosis by inhibiting NKD2/NF-κB pathway. Chrysophanol can potentially prevent CKD by suppressing renal NKD2 expression directly.

The ethnomedicinal and functional uses, phytochemical and pharmacology of compounds from Ardisia species: An updated review.

Medicinal plants are considered to be a critical source of novel compounds and pharmacophores. The genus Ardisia, consisting of approximately 500 species, is the largest genus in the Myrsinaceae family. Ardisia species are widely distributed throughout tropical and subtropical regions of the world and have been used for the treatment of cancer, hypertension, irregular menstruation, gonorrhea, diarrhea and postnatal syndromes, among others. Phytochemical studies of Ardisia species have resulted in the isolation and identification of 111 compounds, including triterpenoid saponins, quinones, phenols, coumarins, cyclic depsipepetide and flavonoids. Crude extracts and isolates from Ardisia have been reported to have in vitro and in vivo efficacies, including but not limited to anticancer, antiinflammatory, antimicrobial, antioxidant, antithrombotic and antidiabetic, antitubercular compounds. This review focuses on the medical and functional uses, phytochemical profile and pharmacological efficacies of Ardisia species over the past 15 years. This review will provide information indicating that Ardisia species represent an invaluable source of potential therapeutic compounds.

Efficacy and safety of long-term transcutaneous electroacupuncture versus sham transcutaneous electroacupuncture for delayed gastric emptying after distal gastrectomy: study protocol for a randomized, patient-assessor blinded, controlled trial.

BACKGROUND: Delayed gastric emptying (DGE) after distal gastrectomy impacts patients' nutritional status and quality of life. The current treatments of DGE seem unsatisfactory or need invasive interventions. It is unknown whether transcutaneous electroacupuncture (TEA) is effective in treating DGE. METHODS: A total of 90 eligible participants who underwent distal gastrectomy will be randomly allocated to either the TEA group (n = 60) or the sham transcutaneous electroacupuncture (sham-TEA) group (n = 30). Each participant will receive TEA on the bilateral acupoints of Zusanli (ST36) and Neiguan (PC6) for 4 weeks. The primary outcomes will be the residual rates of radioactivity in the stomach by gastric scintigraphy and total response rates. The secondary outcomes will be endoscopic features, autonomic function, nutritional and psychological status, serum examination, and quality of life (QoL). The adverse events will also be reported. The patients will be followed up 1 year after the treatment. DISCUSSION: The findings of this randomized trial will provide high-quality evidence regarding the efficacy and safety of long-term TEA for treating DGE after distal gastrectomy. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000033965. Registered on 20 June 2020.

DYRK1B-STAT3 Drives Cardiac Hypertrophy and Heart Failure by Impairing Mitochondrial Bioenergetics.

BACKGROUND: Heart failure is a global public health issue that is associated with increasing morbidity and mortality. Previous studies have suggested that mitochondrial dysfunction plays critical roles in the progression of heart failure; however, the underlying mechanisms remain unclear. Because kinases have been reported to modulate mitochondrial function, we investigated the effects of DYRK1B (dual-specificity tyrosine-regulated kinase 1B) on mitochondrial bioenergetics, cardiac hypertrophy, and heart failure. METHODS: We engineered DYRK1B transgenic and knockout mice and used transverse aortic constriction to produce an in vivo model of cardiac hypertrophy. The effects of DYRK1B and its downstream mediators were subsequently elucidated using RNA-sequencing analysis and mitochondrial functional analysis. RESULTS: We found that DYRK1B expression was clearly upregulated in failing human myocardium and in hypertrophic murine hearts, as well. Cardiac-specific DYRK1B overexpression resulted in cardiac dysfunction accompanied by a decline in the left ventricular ejection fraction, fraction shortening, and increased cardiac fibrosis. In striking contrast to DYRK1B overexpression, the deletion of DYRK1B mitigated transverse aortic constriction-induced cardiac hypertrophy and heart failure. Mechanistically, DYRK1B was positively associated with impaired mitochondrial bioenergetics by directly binding with STAT3 to increase its phosphorylation and nuclear accumulation, ultimately contributing toward the downregulation of PGC-1α (peroxisome proliferator-activated receptor gamma coactivator-1α). Furthermore, the inhibition of DYRK1B or STAT3 activity using specific inhibitors was able to restore cardiac performance by rejuvenating mitochondrial bioenergetics. CONCLUSIONS: Taken together, the findings of this study provide new insights into the previously unrecognized role of DYRK1B in mitochondrial bioenergetics and the progression of cardiac hypertrophy and heart failure. Consequently, these findings may provide new therapeutic options for patients with heart failure.

Tea polyphenol/glycerol-treated double-network hydrogel with enhanced mechanical stability and anti-drying, antioxidant and antibacterial properties for accelerating wound healing.

Frequent dressing changes can result in secondary wound damage. Therefore, it is of great significance to construct a wound dressing that can be used for a long time without changing. Here, a double-network hydrogel was synthesized through hydrogen bonding interactions of tea polyphenol (TP)/glycerol with photo-crosslinked N-acryloyl glycinamide (NAGA), gelatin methacrylate (GelMA), and nanoclay hydrogel. The glycerol/water solvent slowed the diffusion of TP into the NAGA/GelMA/Laponite (NGL)hydrogel, thereby avoiding excessive crosslinking, and forming a uniform network. The hydrogel exhibited excellent water retention (84% within 28 days). Additionally, due to the hygroscopicity of glycerol, the hydrogel's mechanical strength (0.73-1.14 MPa) and tensile strain (207%-353%) increased further after 14 days in an open environment. Additionally, the hydrogel exhibited superior anti-ultraviolet and antioxidant properties, which effectively alleviated the wound site's oxidative stress and accelerated wound healing. Moreover, antibacterial activity was observed against both E. coli and S. aureus in the hydrogel wound dressing. Thus, by promoting wound closure, angiogenesis and collagen deposition, the double-network NGLG20/TG hydrogel dressing can successfully accelerate wound healing. The multifunctional double-network hydrogel, therefore, shows immense potential as an ideal candidate for wound dressings because it is long-lasting and prevents secondary damage caused by frequent dressing changes.

2-(2-phenylethyl)chromone-enriched extract of the resinous heartwood of Chinese agarwood (Aquilaria sinensis) protects against taurocholic acid-induced gastric epithelial cells apoptosis through Perk/eIF2α/CHOP pathway.

BACKGROUND: Injury of gastric epithelial cells is one of the most important pathological features of bile reflux gastritis. Chinese agarwood (the resinous heartwood of Aquilaria sinensis) has been used to treat stomach problems for thousands of years in China. However, the pathological mechanism of epithelial cells death induced by bile acids and the therapeutic target of Chinese agarwood for improving bile reflux gastritis have not yet been fully clarified. PURPOSE: This study aimed to investigate the pro-apoptotic effect of taurocholic acid (TCA) by regulating the ER stress pathway. Moreover, the role of Chinese agarwood 2-(2-phenylethyl)chromone-enriched extract (CPE) to inhibit gastric epithelial cell death induced by TCA was also been demonstrated. METHODS: We adopted human gastric epithelial GES-1 cells to explore the mechanism of TCA-induced cell death in vitro. Then the cell viability, apoptosis rate, and protein expressions were evaluated to explore the protective effects of CPE on GES-1 cells by TCA injury. The therapeutic effect of CPE on bile reflux gastritis was further confirmed by the bile reflux mice in vivo. RESULTS: Our results demonstrated that TCA activated GES-1 cell apoptosis by increased cleavage of caspase-7 and PARP. Further experiments showed that TCA up-regulated endoplasmic reticulum (ER) stress, subsequently triggered the apoptosis of the epithelial cells. Our research explored that CPE is the main effective fraction in Chinese agarwood by preventing the TCA-induced gastric epithelial cell injury. CPE effectively suppressed GES-1 cell apoptosis activated by TCA through inhibiting Perk/eIF2α/CHOP pathway. The anti-apoptotic effect of CPE on gastric mucosa had also been confirmed in vivo. Moreover, the main effective components in CPE corresponding to the protection of epithelial cells were also been identified. CONCLUSION: Our finding suggested that CPE recovered the TCA-induced epithelial cell apoptosis by mediating the activation of ER stress, which explored potential medicine to treat bile reflux gastritis.

A brief review and case report of urothelial carcinoma and metachronous leiomyosarcoma of the bladder at the same anatomic region.

One patient with bladder leiomyosarcoma and urothelial carcinoma is very rare. Only 10 cases have been reported in the literature. A 70-year-old patient was admitted due to bladder tumor. Two TURBTs were performed confirming the patient was free of tumor, and pathology reported low-grade urothelial carcinoma. Three years later, a tumor was also found on the right anterolateral wall of urinary bladder and was diagnosed as leiomyosarcoma by pathological examination. Radical cystectomy was performed. With 45 months follow-up, the patient has no recurrence. Two malignancies in the same anatomic region at different time has never been reported to date.

5-Hydroxymethylfurfural Alleviates Inflammatory Lung Injury by Inhibiting Endoplasmic Reticulum Stress and NLRP3 Inflammasome Activation.

5-Hydroxymethylfurfural (5-HMF) is a common reaction product during heat processing and the preparation of many types of foods and Traditional Chinese Medicine formulations. The aim of this study was to evaluate the protective effect of 5-HMF on endotoxin-induced acute lung injury (ALI) and the underlying mechanisms. Our findings indicate that 5-HMF attenuated lipopolysaccharide (LPS)-induced ALI in mice by mitigating alveolar destruction, neutrophil infiltration and the release of inflammatory cytokines. Furthermore, the activation of macrophages and human monocytes in response to LPS was remarkably suppressed by 5-HMF in vitro through inhibiting the NF-κB signaling pathway, NLRP3 inflammasome activation and endoplasmic reticulum (ER) stress. The inhibitory effect of 5-HMF on NLRP3 inflammasome was reversed by overexpressing ATF4 or CHOP, indicating the involvement of ER stress in the negative regulation of 5-HMF on NLRP3 inflammasome-mediated inflammation. Consistent with this, the ameliorative effect of 5-HMF on in vivo pulmonary dysfunction were reversed by the ER stress inducer tunicamycin. In conclusion, our findings elucidate the anti-inflammatory and protective efficacy of 5-HMF in LPS-induced acute lung injury, and also demonstrate the key mechanism of its action against NLRP3 inflammasome-related inflammatory disorders via the inhibition of ER stress.

[Condensed tannins from roots of Indigofera stachyodes].

Eleven condensed tannins were isolated from the roots of Indigofera stachyodes by various column chromatography techniques including silica gel, octadecyl silica(ODS), Sephadex LH-20, and semi-preparative high performance liquid chromatography(HPLC). These compounds were identified on the basis of physicochemical properties, nuclear magnetic resonance(NMR) and mass spectrometry(MS) data as stachyotannin A(1), epicatechin-(2ß→O→7,4ß→8)-epiafzelechin-(4ß→8)-catechin(2), cinnamtannin D1(3), cinnamtannin B1(4), epicatechin-(2ß→O→7,4ß→8)-epiafzelechin-(4α→8)-epicatechin(5), gambiriin C(6), proanthocyanidin A1(7), proanthocyanidin A2(8), aesculitannin B(9), proanthocyanidin A4(10), and procyanidin B5(11). Compound 1 is a new compound. Compounds 2-11 were isolated from Indigofera for the first time. Furthermore, compounds 1, 2, and 4-11 showed inhibitory effects on thrombin-induced ATP release in platelets.

A novel Apigenin derivative suppresses renal cell carcinoma via directly inhibiting wild-type and mutant MET.

MET, the receptor of hepatocyte growth factor (HGF), is a driving factor in renal cell carcinoma (RCC) and also a proven drug target for cancer treatment. To improve the activity and to investigate the mechanisms of action of Apigenin (APG), novel derivatives of APG with improved properties were synthesized and their activities against Caki-1 human renal cancer cell line were evaluated. It was found that compound 15e exhibited excellent potency against the growth of multiple RCC cell lines including Caki-1, Caki-2 and ACHN and is superior to APG and Crizotinib. Subsequent investigations demonstrated that compound 15e can inhibit Caki-1 cell proliferation, migration and invasion. Mechanistically, 15e directly targeted the MET kinase domain, decreased its auto-phosphorylation at Y1234/Y1235 and inhibited its kinase activity and downstream signaling. Importantly, 15e had inhibitory activity against mutant MET V1238I and Y1248H which were resistant to approved MET inhibitors Cabozantinib, Crizotinib or Capmatinib. In vivo tumor graft study confirmed that 15e repressed RCC growth through inhibition of MET activation. These results indicate that compound 15e has the potential to be developed as a treatment for RCC, and especially against drug-resistant MET mutations.