Search

Abstract Background The triglyceride glucose (TyG) index and triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio are recognized as simple non-insulin-based insulin resistance indices. Our study aimed to explore the relationship between these two indicators and heart failure (HF) in overweight or obesity individuals without diabetes. Methods This cross-sectional study selected 13,473 participants from the National Health and Nutrition Examination Survey (NHANES) 2001–2018 dataset. Weighted multivariable logistic regression and subgroup analysis were employed to evaluate the relationships between TyG index, TG/HDL-C ratio, and HF prevalence, respectively. Additionally, smooth curve fitting was utilized to analyze the dose–response relationships. Results A total of 13,473 obesity or overweight people without diabetes were included in this study through screening, among whom 291 (2.16%) had comorbid HF. The results of multivariable logistic regression suggested that the highest TyG index (OR = 2.4, 95% CI = 1.4–4.2, p = 0.002) and the highest TG/HDL-C ratio (OR = 1.2, 95% CI = 1.1–1.3, p

Cryptococcus neoformans is at the top of the list of “most wanted” human pathogens. Only three classes of antifungal drugs are available for the treatment of cryptococcosis. Studies on antifungal resistance mechanisms are limited to the investigation of how a particular antifungal drug induces resistance to a particular drug, and the impact of stresses other than antifungals on the development of antifungal resistance and even cross-resistance is largely unexplored. The endoplasmic reticulum (ER) is a ubiquitous subcellular organelle of eukaryotic cells. Brefeldin A (BFA) is a widely used chemical inducer of ER stress. Here, we found that both weak and strong selection by BFA caused aneuploidy formation in C. neoformans, mainly disomy of chromosome 1, chromosome 3, and chromosome 7. Disomy of chromosome 1 conferred cross-resistance to two classes of antifungal drugs: fluconazole and 5-flucytosine, as well as hypersensitivity to amphotericin B. However, drug resistance was unstable, due to the intrinsic instability of aneuploidy. We found overexpression of AFR1 on Chr1 and GEA2 on Chr3 phenocopied BFA resistance conferred by chromosome disomy. Overexpression of AFR1 also caused resistance to fluconazole and hypersensitivity to amphotericin B. Furthermore, a strain with a deletion of AFR1 failed to form chromosome 1 disomy upon BFA treatment. Transcriptome analysis indicated that chromosome 1 disomy simultaneously upregulated AFR1, ERG11, and other efflux and ERG genes. Thus, we posit that BFA has the potential to drive the rapid development of drug resistance and even cross-resistance in C. neoformans, with genome plasticity as the accomplice.

Exposure to pesticides induces oxidative stress and deleterious effects on various tissues in non-target organisms. Numerous models investigating pesticide exposure have demonstrated metabolic disturbances such as imbalances in amino acid levels within the organism. One potentially effective strategy to mitigate pesticide toxicity involves dietary intervention by supplementing exogenous amino acids and their derivates to augment the body’s antioxidant capacity and mitigate pesticide-induced oxidative harm, whose mechanism including bolstering glutathione synthesis, regulating arginine-NO metabolism, mitochondria-related oxidative stress, and the open of ion channels, as well as enhancing intestinal microecology. Enhancing glutathione synthesis through supplementation of substrates N-acetylcysteine and glycine is regarded as a potent mechanism to achieve this. Selection of appropriate amino acids or their derivates for supplementation, and determining an appropriate dosage, are of the utmost importance for effective mitigation of pesticide-induced oxidative harm. More experimentation is required that involves large population samples to validate the efficacy of dietary intervention strategies, as well as to determine the effects of amino acids and their derivates on long-term and low-dose pesticide exposure. This review provides insights to guide future research aimed at preventing and alleviating pesticide toxicity through dietary intervention of amino acids and their derivates.

The Charpy impact toughness is a crucial mechanical parameter in the application of materials within the realm of engineering. This study represents the pioneering investigation into the influence of different building directions on the Charpy impact toughness of NiTi shape memory alloys (SMAs) produced via laser powder bed fusion (LPBF). Texture analysis reveals that C0 and C90 exhibit a pronounced // building direction (BA), while C45 demonstrates a strong texture along and . The impact test results demonstrate that C0 exhibits superior impact toughness with an absorbed energy of 12.87 J. The fractured surfaces are examined using the scanning electron microscope (SEM) and transmission electron microscope (TEM). Among them, the electron backscatter diffraction (EBSD) results indicate that the samples with higher geometrically necessary dislocation (GND) and kernel average misorientation (KAM) values can effectively reflect superior impact toughness. In contrast, fewer high-angle grain boundaries (HAGBs) are preferable. Due to the adiabatic effect, the phase transformation of the samples from austenite to martensite doesn't appear under the impact loading. Additionally, this paper discusses the impact of texture orientation, defects, and the relationship between loading direction and deposited layers on the impact toughness of the samples. These findings on impact properties would provide valuable guidance for engineering applications of NiTi SMAs.

Laboratory mutants of Sclerotinia sclerotiorum (Lib) de Bary, resistant to boscalid, have been extensively characterized. However, the resistance situation in the lettuce field remains largely elusive. In this study, among the 172 S. sclerotiorum isolates collected from asparagus lettuce field in Jiangsu Province, China, 132 isolates (76.74%) exhibited low-level resistance to boscalid (BosLR), with a discriminatory dose of 5 μg mL−1. In comparison to the boscalid-sensitive (BosS) isolates, most BosLR isolates demonstrated a slightly superior biological fitness, as evidenced by data on mycelial growth, sclerotium production and pathogenicity. Moreover, most BosLR isolates showed comparable levels of oxalic acid (OA) accumulation, increased exopolysaccharide (EPS) content and reduced membrane permeability when compared to the BosS isolates. Nevertheless, their responses to distinct stress factors diverged significantly. Furthermore, the effectiveness of boscalid in controlling BosLR isolates on radish was diminished compared to its efficacy on BosS isolates. Genetic mutations were identified in the SDH genes of BosLR isolates, revealing the existence of three resistant genotypes: I (A11V at SDHB, SDHBA11V), II (Q38R at SDHC, SDHCQ38R) and III (SDHBA11V+SDHCQ38R). Importantly, no cross-resistance was observed between boscalid and other fungicides such as thifluzamide, pydiflumetofen, fluazinam, or tebuconazole. Our molecular docking analysis indicated that the docking total score (DTS) of the type I resistant isolates (1.3993) was lower than that of the sensitive isolates (1.7499), implying a reduced affinity between SDHB and boscalid as a potential mechanism underlying the boscalid resistance in S. sclerotiorum. These findings contribute to an enhanced comprehension of boscalid’s mode of action and furnish valuable insights into the management of boscalid resistance.

Summary: Most complex prime links exhibit inherent topological chirality, yet their high stereoinduction remains a rare occurrence. Here, we present a protocol for the stereoselective synthesis of a molecular link comprising two triple entwined rings. We describe steps for constructing the precursor circular helicate, performing ring closure metathesis, and demetallation. We also outline procedures for bio-beads separation and data analysis. This protocol holds promise for applications in molecular nanotopology.For complete details on the use and execution of this protocol, please refer to Zhang et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

In this paper, a past information-based fault detection (FD) interval observer is designed for linear time-invariant discrete-time system with external disturbances. The past outputs, upper and lower estimations in a finite time window are applied to construct observer. Design freedom of the FD observer is raised by introducing the gain matrices of past information. The interval property is realized through time-delay positive systems theory and the undetermined observer matrices is solved with disturbance attenuation, fault sensitivity and nonnegativity conditions. The decision is implemented by residual interval and natural threshold. Finally, simulation is proceeded to declare the FD performance.

Summary: Here, we present a protocol for the complete stereoselective synthesis of a molecular 51 knot. Enantiopure chiral ligands serve as the starting point, while Zn(OTf)2 acts as the template, facilitating the quantitative formation of pentameric circular helicates with 100% d.e. A subsequent sequence of ring-closing metathesis and demetalation steps transforms the structure into a fully organic 51 knot. This protocol expands the scope of strategies employed for chiral knot preparation and paves the way for more complex molecular topologies.For complete details on the use and execution of this protocol, please refer to Zhang et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

In this paper, the effects of maize and its three intercropping plants, sweet potato, soybean and peanut, on the growth and development of FAW, feeding preference of larvae, olfactory response and oviposition preference of adults were studied in the laboratory. The results showed that maize and peanut were suitable for the survival and development of FAW, while sweet potato and soybean were not suitable for multigenerational reproduction. The larvae significantly preferred to feed on maize compared to the other three plants. The olfactory response test indicated that soybean showed a strong deterrent effect against FAW adults. Furthermore, the intercropping plants reduced the host selection rate of adults compared to maize alone. In two-choice tests of the maize vs. the intercropping plants, the female adult preferred to oviposit and lay more eggs on maize rather than on the intercropping plants. The intercropping plants significantly reduced the oviposition selection of FAW adults when the combination (maize + intercropping plant), especially soybean and sweet potato, was compared to maize alone. These may be the reasons for why the maize–soybean intercropping system reduced FAW damage in the field. We also speculated that the maize–sweet potato system may also reduce the FAW damage. This study provided a theoretical basis for the comprehensive management of FAW by utilizing an intercropping system.

The Shimensi deposit is a recently discovered W-Cu-Mo polymetallic deposit located in the Jiangnan porphyry-skarn W belt in South China. The deposit has a resource of 0.74×106 t of WO3 accompanied by 0.4×106 t Cu and 28000 t Mo and other useful components like Ga, making it one of the largest W deposits in the world. This paper is aimed to reveal the ore-controlling mechanisms of the Shimensi deposit, involving the role of the ore-related granites, the tectonic background for its formation, and the metallogenesis model. The systematic geological survey suggests multi-types of alteration are developed in the deposit, mainly including greisenization, potassic-alteration, sericitization, chloritization, and silicification. Drilling engineering data and mining works indicate that the Shimensi deposit consists of two main orebodies of I and II. Therein, the W resource has reached a supergiant scale, and the accompanied Cu, Mo, Au, Bi, Ga, and some other useful components are also of economic significance. The main ore-minerals consist of scheelite, wolframite and chalcopyrite. Disseminated mineralization is the dominant type of the W-Cu-Mo polymetallic orebodies, and mainly distributes in the inner and external contact zone that between the Neoproterozoic biotite granodiorite and the Yanshanian granites. The main orebody occurs at the external contact zone, and the pegmatoid crust near the inner contact zone is an important prospecting marker of the W mineralization. Of them, the disseminated W ores within the wall rock of the Neoproterozoic biotite granodiorite is a new mineralization type identified in this paper. Combining previous geochronological and isotopic data, we propose that the mineralization of the Shimensi deposit is closely related to the intruding of the Yanshanian porphyritic biotite granite and granite porphyry. Geochemical data suggest that the biotite granodiorite is rich in Ca and had provided a large amount of Ca for the precipitation of scheelite in this area. Thus, it is a favorable wall rock type for W mineralization. The Shimensi deposit belongs to granitic-type W polymetallic deposit related to post-magmatic hydrothermal, and the ore-forming fluid was initially derived from the Yanshanian magmas.©2022 China Geology Editorial Office.

Abstract Background There is still controversy regarding the associations of urinary albumin excretion (UAE) and estimated glomerular filtration rate (eGFR) with atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Therefore, it is necessary to explore the correlation between them in T2DM patients. Methods We conducted a survey involving 2565 T2DM patients from a single center. The study cohort was classified into three groups based on the levels of albuminuria: normal UAE (UAE

The aging population and high incidence of age-related diseases are major global societal issues. Consuming bioactive substances as part of our diet is increasingly recognized as essential for ensuring a healthy life for older adults. Wheat germ protein has a reasonable peptide structure and amino acid ratio but has not been fully utilized and exploited, resulting in wasted wheat germ resources. This review summarizes reformational extraction methods of wheat germ protein/peptides (WGPs), of which different methods can be selected to obtain various WGPs. Interestingly, except for some bioactive activities found earlier, WGPs display potential anti-aging activity, with possible mechanisms including antioxidant, immunomodulatory and intestinal flora regulation. However, there are missing in vitro and in vivo bioactivity assessments of WGPs. WGPs possess physicochemical properties of good foamability, emulsification and water retention and are used as raw materials or additives to improve food quality. Based on the above, further studies designing methods to isolate particular types of WGPs, determining their nutritional and bioactive mechanisms and verifying their activity in vivo in humans are crucial for using WGPs to improve human health.

Molecular targeting and immunotherapy provide durable responses for advanced lung cancer clinical therapy in many patients. However, the mechanisms of occurrence of progressive disease and resistance to targeted therapy and immunotherapy have not been elucidated. Herein, we report two cases of small cell transformation of non-small cell lung cancer (NSCLC) after targeted therapy or immunotherapy. The first case was a 63-year-old female patient presenting with cough and expectoration. Left lung invasive adenocarcinoma was diagnosed after left lung tumor biopsy. After epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) targeted therapy for almost 2 years, disease progression and symptom aggravation were observed. Pathological and immunohistochemical staining results after biopsy revealed small cell lung cancer (SCLC). The second case was a 75-year-old male patient diagnosed with stage IV squamous cell carcinoma of the lung, who received carboplatin/paclitaxel adjuvant chemotherapy and pembrolizumab treatment with partial response. Disease progression and metastasis occurred within 15 cycles of immunotherapy. Computed tomography revealed a lower left lung tumor. Cytological examination of lung lavage fluid and biopsy under thoracoscope revealed SCLC. In conclusion, histological transformation to SCLC is a potential mechanism of NSCLC resistance to targeted therapy or immunotherapy. During treatment, clinicians should monitor serum tumor markers or genome sequencing, particularly in patients with disease progression, as this may be beneficial for early detection of SCLC transformation. Repeated biopsy can be performed if necessary, and the therapeutic regimen can be adjusted in a timely manner according to the results of molecular pathological tests for personalization and whole-process management.

Background The association of serum retinol-binding protein (RBP) levels with nonalcoholic fatty liver disease (NAFLD) remains controversial. Furthermore, few studies have investigated their relationship in type 2 diabetes mellitus (T2DM) patients. Therefore, the aim of the present study was to explore the association between serum RBP levels and NAFLD in Chinese inpatients with T2DM. Methods This cross-sectional, real-world study included 2,263 Chinese T2DM inpatients. NAFLD was diagnosed by abdominal ultrasonography. The subjects were divided into four groups based on RBP quartiles, and clinical characteristics were compared among the four groups. The associations of both RBP levels and quartiles with the presence of NAFLD were also analyzed. Results After adjustment for sex, age, and diabetes duration, there was a significant increase in the prevalence of NAFLD from the lowest to the highest RBP quartiles (30.4%, 40.0%, 42.4%, and 44.7% for the first, second, third, and fourth quartiles, respectively, P

Abstract The Coronavirus disease 2019 (COVID-19) pandemic is still spread and has made a severe public health threat around the world. To improve disease progression, emerging Chinese herbal compounds were used in clinical practice and some agents have proven beneficial in treating COVID-19. Here, the relevant literature from basic researches to clinical application were identified and comprehensively assessed. A variety of Chinese herbal compounds have been reported to be effective in improving symptoms and outcomes in patients with COVID-19, particularly together with routine treatment strategy. The pharmacological activities were mainly attributed to the relief of clinical symptoms, inhibition of cytokine storm, and improvement of organ function. Besides, the development of novel antiviral drugs from medicinal herbs were further discussed. The updated laboratory and clinical studies provided the evidence of Chinese herbal compounds such as Lianhua Qingwen prescription, Shufeng Jiedu prescription, and Qingfei Paidu Tang for the relief of COVID-19. However, both of the randomized controlled trials and real world researches need to be done for supporting the evidence including the efficacy and safety in fighting COVID-19.

As one of the most important avian immunosuppressive and neoplastic diseases, Marek’s disease (MD), caused by oncogenic Marek’s disease virus (MDV), has caused huge economic losses worldwide over the past five decades. In recent years, MD outbreaks have occurred frequently in MD-vaccinated chicken flocks, but the key pathogenic determinants and influencing factors remain unclear. Herein, we analyzed the pathogenicity of seven newly isolated MDV strains from tumor-bearing chickens in China and found that all of them were pathogenic to chicken hosts, among which four MDV isolates, SDCW01, HNXZ05, HNSQ05 and HNSQ01, were considered to be hypervirulent MDV (HV-MDV) strains. At 73 days of the virus infection experiment, the cumulative incidences of MD were 100%, 93.3%, 90% and 100%, with mortalities of 83.3%, 73.3%, 60% and 86.7%, respectively, for the four viruses. The gross occurrences of tumors were 50%, 33.3%, 30% and 63.3%, respectively, accompanied by significant hepatosplenomegaly and serious atrophy of the immune organs. Furthermore, the immune protection effects of four commercial MD vaccines against SDCW01, CVI988, HVT, CVI988+HVT, and 814 were explored. Unexpectedly, during the 67 days of post-virus challenge, the protection indices (PIs) of these four MD vaccines were only 46.2%, 38.5%, 50%, and 28%, respectively, and the birds that received the monovalent CVI988 or HVT still developed tumors with cumulative incidences of 7.7% and 11.5%, respectively. To our knowledge, this is the first demonstration of the simultaneous comparison of the immune protection efficacy of multiple commercial MD vaccines with different vaccine strains. Our study revealed that the HV-MDV variants circulating in China could significantly break through the immune protection of the classical MD vaccines currently widely used. For future work, there is an urgent need to develop novel, more effective MD vaccines for tackling the new challenge of emerging HV-MDV strains or variants for the sustainable control of MD.

The health effects of exposure to secondary organic aerosols (SOAs) are still limited. Here, we investigated and compared the toxicities of soot particles (SP) coated with β-pinene SOA (SOAβPin-SP) and SP coated with naphthalene SOA (SOANap-SP) in a human bronchial epithelial cell line (BEAS-2B) residing at the air–liquid interface. SOAβPin-SP mostly contained oxygenated aliphatic compounds from β-pinene photooxidation, whereas SOANap-SP contained a significant fraction of oxygenated aromatic products under similar conditions. Following exposure, genome-wide transcriptome responses showed an Nrf2 oxidative stress response, particularly for SOANap-SP. Other signaling pathways, such as redox signaling, inflammatory signaling, and the involvement of matrix metalloproteinase, were identified to have a stronger impact following exposure to SOANap-SP. SOANap-SP also induced a stronger genotoxicity response than that of SOAβPin-SP. This study elucidated the mechanisms that govern SOA toxicity and showed that, compared to SOAs derived from a typical biogenic precursor, SOAs from a typical anthropogenic precursor have higher toxicological potency, which was accompanied with the activation of varied cellular mechanisms, such as aryl hydrocarbon receptor. This can be attributed to the difference in chemical composition; specifically, the aromatic compounds in the naphthalene-derived SOA had higher cytotoxic potential than that of the β-pinene-derived SOA.

Abstract Background Hyaluronan (HA) metabolism by chondrocytes is important for cartilage development and homeostasis. However, information about the function of circular RNAs (circRNAs) in HA metabolism is limited. We therefore profiled the role of the novel HA-related circRNA circHYBID in the progression of osteoarthritis (OA). Methods CircHYBID function in HA metabolism in chondrocytes was investigated using gain-of-function experiments, and circHYBID mechanism was confirmed via bioinformatics analysis and luciferase assays. The expression of circHYBID–hsa-miR-29b-3p–transforming growth factor (TGF)-β1 axis was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. CircHYBID, TGF-β1, and HA levels in cartilage samples were evaluated using qRT-PCR and pathological examination. Enzyme-linked immunosorbent assay was used to assess HA accumulation in chondrocyte supernatant. Results CircHYBID expression was significantly downregulated in damaged cartilage samples compared with that in the corresponding intact cartilage samples. CircHYBID expression was positively correlated with alcian blue score. Interleukin-1β stimulation in chondrocytes downregulated circHYBID expression and decreased HA accumulation. Gain-of-function experiments revealed that circHYBID overexpression in chondrocytes increased HA accumulation by regulating HA synthase 2 and HYBID expression. Further mechanism analysis showed that circHYBID upregulated TGF-β1 expression by sponging hsa-miR-29b-3p. Conclusions Our results describe a novel HA-related circRNA that could promote HA synthesis and accumulation. The circHYBID–hsa-miR-29b-3p–TGF-β1 axis may play a powerful regulatory role in HA metabolism and OA progression. Thus, these findings will provide new perspectives for studies on OA pathogenesis, and circHYBID may serve as a potential target for OA therapy.

Gamma-aminobutyric acid (GABA), known as the most abundant inhibitory neurotransmitter in the mammalian brain, can permeate ruminal epithelia by passive diffusion and enrich in the rumen environment. To explore whether the addition of GABA can regulate rumen fermentation characteristics as well as methane production, a 2 × 6 factorial in vitro rumen batch culture was conducted to determine the supplemental effect of GABA at inclusion levels of 0 (Control), 10, 20, 30, 40 and 50 mg in culture fluids on rumen fermentation of two total mixed rations (HF—a high-fiber ration consisted of 70% corn silage and 30% concentrate; and LF—a low-fiber ration consisted of 30% corn silage and 70% concentrate). After 72 h in vitro incubation of two rations with mixed rumen microoganisms obtained from five rumen-cannulated lactating Holstein dairy cows, increasing GABA addition linearly increased cumulative gas production in the LF group, though in vitro dry matter digestibility was not affected in either the LF or HF group. Kinetic gas production analysis noted that increasing GABA addition mostly decreased the gas production rate (i.e., RmaxG), as well as the ration digestion rate (RmaxS) to reach maximum fermentation. The GABA addition did not affect pH or microbial growth (i.e., MCP). However, total volatile fatty acid production in both LF and HF groups all linearly increased with the increase in GABA addition. Along with the increase in GABA addition in both LF and HF groups, the ratio of non-glucogenic to glucogenic volatile fatty acids both increased, while the molar proportions of propionate and valerate were significantly decreased, and the acetate and butyrate proportions were increased after 72 h in vitro rumen fermentation. The time-course change of fermentation end-products generally showed that carbon dioxide declined from approximately 89% to 74%, and methane increased from approximately 11% to 26%. After 72 h in vitro fermentation, molar methane proportion was greater in the LF than in the HF group, and increasing GABA addition quadratically increased methane production in the LF group while a slight increase occurred in the HF group.

Abstract Background One-stop occlusion, which is defined as the combination of atrial septal defect [ASD] or patent foramen ovale [PFO] occlusion and left atrial appendage [LAA] closure, in patients with ASD/PFO and atrial fibrillation (AF) has not yet been investigated systematically. This study aimed to evaluate the safety and efficacy of one-stop occlusion in the treatment of adult patients with ASD/PFO and AF. Methods Inpatients with AF and ASD/PFO were recruited between August 2014 and April 2019. Preoperatively, transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) were conducted to identify the ASD/PFO size and margin, presence of thrombus in the LAA, and LAA orifice width and depth at 0°, 45°, 90°, and 135°. After confirmation of the indications of LAA closure (LAAC) and ASD/PFO occlusion, the procedures were performed simultaneously under general anesthesia. Oral anticoagulants were administered for 45–60 days, followed with regular evaluation of TTE and TEE. Results Forty-nine patients (age, 65.6 ± 9.6 years) were recruited in this study, including 24 patients with ASD and 25 patients with PFO. They were treated with LAAC and ASD/PFO occlusion successfully. The mean ASD size and mean diameter of the ASD occluders were 14.2 ± 7.7 and 25.4 ± 8.5 mm, respectively. The mean PFO size was 3.5 ± 0.4 mm. The mean maximal LAA orifice width and depth were 20.5 ± 3.4 and 28.3 ± 3.6 mm, respectively. All patients were implanted with a Watchman device (diameter, 27.1 ± 2.9 mm). Postoperatively, all patients took anticoagulants orally for 45–60 days, and their mean postoperative follow-up duration was 29.0 ± 12.1 months. Postoperative TEE showed that all had normal positioning of the LAA and ASD/PFO occluders. At 45–60 days after operation, TEE showed that the LAA and ASD/PFO occluder were in the normal position; however, two patients who took warfarin and novel oral anticoagulants, respectively, have developed occluder thrombosis. After adjusted anticoagulant therapy, TEE showed that the thrombus disappeared at 6 months after operation. Conclusion One-stop occlusion is safe and effective for the treatment of adult patients with ASD/PFO and AF. It is also feasible to administer warfarin or novel oral anticoagulants after operation.

AimsOur aim was to evaluate the separate and combined effects of maternal pre-pregnancy obesity and gestational abnormal glucose metabolism (GAGM) on adverse perinatal outcomes.MethodsA total of 2,796 Chinese pregnant women with singleton delivery were studied, including 257 women with pre-pregnancy obesity alone, 604 with GAGM alone, 190 with both two conditions, and 1,745 with neither pre-pregnancy obesity nor GAGM as control group. The prevalence and risks of adverse pregnancy outcomes were compared among the four groups.ResultsCompared with the normal group, pregnant women with maternal pre-pregnancy obesity alone, GAGM alone, and both two conditions faced significantly increased risks of pregnancy-induced hypertension (PIH) (odds ratio (OR) 4.045, [95% confidence interval (CI) 2.286–7.156]; 1.993 [1.171–3.393]; 8.495 [4.982–14.485]), preeclampsia (2.649 [1.224–5.735]; 2.129 [1.128–4.017]; 4.643 [2.217–9.727]), cesarean delivery (1.589 [1.212–2.083]; 1.328 [1.095–1.611]; 2.627 [1.908–3.617]), preterm delivery (1.899 [1.205–2.993]; 1.358 [0.937–1.968]; 2.301 [1.423–3.720]), macrosomia (2.449 [1.517–3.954]; 1.966 [1.356–2.851]; 4.576 [2.895–7.233]), and total adverse maternal outcomes (1.762 [1.331–2.332]; 1.365 [1.122–1.659]; 3.228 [2.272–4.587]) and neonatal outcomes (1.951 [1.361–2.798]; 1.547 [1.170–2.046]; 3.557 [2.471–5.122]). Most importantly, there were no obvious risk differences in adverse pregnancy outcomes between maternal pre-pregnancy obesity and GAGM group except PIH, but pregnant women with both obesity and GAGM exhibited dramatically higher risks of adverse pregnancy outcomes than those with each condition alone.ConclusionsMaternal pre-pregnancy obesity and GAGM were independently associated with increased risks of adverse pregnancy outcomes. The combination of pre-pregnancy obesity and GAGM further worsens adverse pregnancy outcomes compared with each condition alone.

Background: The outbreak of Coronavirus disease 2019 (COVID-19) has caused more than 180 million infections and 3.9 million deaths. To date, emerging clinical evidence has shown the synergetic benefits of Chinese herbal injections in treating this contagious respiratory disease. This review aims to summarize and analyze the efficacy and safety of Chinese herbal injections in the therapy of COVID-19. Methods: The literature from 3 electronic databases, PubMed, CNKI, and Web of Science, were searched using the search terms “COVID-19”, “SARS-CoV-2”, “traditional Chinese medicine”, “herb”, “herbal”, and “injection”. Then the identified articles were comprehensively evaluated. Results: Limited data demonstrated that Chinese herbal injections could significantly improve the clinical outcomes of COVID-19 patients, especially in combination with conventional treatment strategies. The benefits of which were mainly associated with the relief of symptoms, prevention of secondary infection, regulation of inflammation and immune function. There was also evidence showing the inhibitory effects on SARS-CoV-2 replication in vitro. Nevertheless, available real-world data suggested the increased risk of adverse event. Furthermore, the defects of existing researches and the insights for discovering novel antiviral drugs were prospectively discussed. Conclusion: Evidence-based advances revealed that Chinese herbal injections such as XueBiJing injection and ShenMai injection, exerted potent effects against COVID-19. Further laboratory researches and clinical evaluation are needed to gather scientific evidence on the efficacy and safety.

Background: Controversies concerning the association between insulin therapy and atherosclerotic lesions in type 2 diabetes mellitus (T2DM) remain to exist. The purpose of this study was to investigate whether insulin therapy in T2DM patients is linked with the increased risk of carotid atherosclerosis in real-world settings.Methods: We retrospectively enrolled 2,356 hospitalized patients with T2DM, including 1,716 subjects receiving insulin therapy and 640 subjects without receiving insulin therapy. Carotid atherosclerotic lesions including carotid intima-media thickness (CIMT), carotid plaque and carotid stenosis were assessed by Doppler ultrasonography and were compared between T2DM patients treated with and without insulin.Results: After adjusting for age and duration of diabetes, there was a significant increase in the prevalence of carotid plaque in both men (52.0 vs. 41.7%, p = 0.007) and women (49.6 vs. 39.7%, p = 0.003) receiving insulin therapy than in those without receiving insulin therapy. After further controlling for other confounding factors, compared with the patients without receiving insulin therapy, the risk of carotid plaque was still significantly increased not only in women treated with insulin (OR: 1.810; 95% CI: 1.155–2.837, p = 0.010), but also in men treated with insulin (OR: 1.867; 95% CI: 1.307–2.666; p = 0.001). Additionally, HOMA2-B% was higher in both women and men without receiving insulin therapy compared with those receiving insulin therapy (p < 0.001 in both men and women), but HOMA-IR was significantly higher in patients treated with insulin than in those without receiving insulin therapy (p < 0.001 in both men and women).Conclusions: Insulin therapy is associated with markedly increased risk of carotid atherosclerotic lesions in type 2 diabetes, which partly attribute to the more serious insulin resistance in T2DM patients receiving insulin therapy.

AIM:To observe and analyze the effect of non-mydriatic fundus photography in screening diabetic retinopathy(DR), so as to provide the basis for clinical screening.METHODS:In our hospital from December 2016 to November 2017, 120 patients(240 eyes)was diagnosed as diabetes(DM), which were treated as the subjects of observation. By the same operator with non-mydriatic fundus photography, fundus photography and 7 range fundus fluorescein angiography(FFA)after mydriasis were taken. Taking the international clinical classification of diabetic retinopathy(DR)as the standard, the above three examinations were review, grade and record by the same physician by blind method. The fundus fluorescein angiography as the gold standard, the other two results were compared to detect the sensitivity, specificity, Youden index, Kappa value of the two for DR with different grade.RESULTS: There was 70.0% eyes diagnosed as diabetic retinopathy after screened by fundus angiography, 66.7% by post-mydriatic fundus photography, 65.0% by non-mydriatic fundus photography. The grading results of diabetic retinopathy screened by different methods were basically consistent, with no significant difference(P>0.05). When screening for diabetic retinopathy of different degrees, the sensitivity and specificity of the non-mydriatic group were 92.9% and 90.3%, respectively. There was no significant difference between the results of the non-mydriatic group and the non-mydriatic group. Compared with the gold standard group(FFA), the Youden index(83.14%)was close to 1, with high reliability; Kappa=0.81, and the validation was consistent. When screening for moderately nonproliferative diabetic retinopathy, the sensitivity and specificity of non-mydriatic fundus photography were 90.6% and 95.5%; there was no significant difference between the results of non-mydriatic and the results of fundus photography after mydriasis. Compared to the gold standard group, the Youden index was 86.09%, the reliability is high, Kappa=0.86, and the test was consistency. CONCLUSION:Non-mydriatic fundus photography can be used as a simple and accurate method for screening diabetic retinopathy. It is simple and easy to carry out without risk. It is easy to train specialist technicians for multi-point operation. With the help of today's convenient network, the image is transmitted to an experienced ophthalmologist for reading and diagnosis, which is convenient and fast, so that the patient can be diagnosed and treated nearby, which has positive significance for the society.

Several epidemiological studies reported that chronic arsenic exposure increased risk of prostate cancer. This study aimed to investigate whether chronic NaAsO2 exposure elevates stemness and chemoresistance in prostate cancer cells. DU145 (wild-type p53) and PC-3 (p53-null) cells were exposed to NaAsO2 (2 μmol/L) for 30 generations. IC50s to docetaxel and cisplatin were increased in NaAsO2-exposed DU145 and PC-3 cells. The number of tumor spheres was elevated in NaAsO2-exposed DU145 and PC-3 cells. Nanog, SOX-2 and ALDH1A1, three markers of cancer stemness, were upregulated in NaAsO2-exposed PC-3 spheres. Moreover, NaAsO2-exposed DU145 and PC-3 cells were arrested in G2/M phase. Histone H2AX phosphorylation on Ser139, an indicator for DNA double-strand break, was upregulated in NaAsO2-exposed DU145 and PC-3 cells. ATM phosphorylation on Ser1981, a key sensor of genotoxic stress, was rapidly elevated in NaAsO2-exposed DU145 cells. Phosphor-p53, a downstream molecule of ATM signaling, and p21, a direct target of p53, were upregulated in NaAsO2-exposed DU145 cells. Unexpectedly, p21 was also elevated in NaAsO2-exposed p53-null PC-3 cells. Antioxidant NAC alleviated NaAsO2-induced ATM phosphorylation, cell cycle arrest, and subsequent stemness enhancement and chemoresistance in both DU145 and PC-3 cells. These results suggest that ROS-mediated genotoxic stress is involved in NaAsO2-induced cell cycle arrest, stemness enhancement and chemoresistance of prostate cancer cells in a p53-independent manner.

This study explored the effects of renal sympathetic denervation (RDN) on hyperlipidity-induced cardiac hypertrophy in beagle dogs. Sixty beagles were randomly assigned to the control group, RDN group, or sham-operated group. The control group was fed with a basal diet, while the other two groups were given a high-fat diet to induce model hypertension. The RDN group underwent an RDN procedure, and the sham-operated group underwent only renal arteriography. At 1, 3, and 6 months after the RDN procedure, the diastolic blood pressure (DBP) and systolic blood pressure (SBP) levels were markedly decreased in the RDN group relative to the sham group (P

Background: An outbreak of Coronavirus Disease 2019 (COVID-19) which was infected by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is still spreading and has led to unprecedented health emergency over the world. Though no specific drug has been developed so far, emerging agents have been confirmed effective or potentially beneficial to restrain it. Lianhua Qingwen (LHQW) is a commonly used Chinese medical preparation to treat viral influenza, including in the fight against SARS in 2002–2003 in China. Recent data also showed that LHQW played a vigorous role in COVID-19 treatment. Purpose: This review will elucidate the pre-clinical and clinical evidence of LHQW in lung protection and antiviral activities, and provide timely data delivery for the exploration of effective treatment strategies in the therapy of COVID-19. Study design and method: The research data were obtained from the academic databases (up to August 8, 2020) including Pubmed, CNKI and Web of Science, on ethnobotany and ethno medicines. The search keywords for screening the literature information were “virus”, “COVID-19”, or “SARS-CoV-2”, and “Lianhua Qingwen”. The documents were filtered and summarized for final evaluation. Results: The collected evidence demonstrated that LHQW exhibited benefits against COVID-19. Impressively, LHQW in conjunction with conventional treatment could significantly improve COVID-19 patients as a synergetic strategy. The mechanisms were mainly involved the antiviral activity, and regulation of inflammation response as well as immune function. Conclusion: Although the data were far from adequate, the latest advances had shown the benefits of LHQW in COVID-19, especially in combination with other antiviral drugs. This review provides comprehensive evidence of LHQW as a complementary strategy for treating COVID-19. Nevertheless, imperious researches should be conducted to clarify the unconfirmed effects, regulatory mechanisms and adverse reactions of LHQW in treating COVID-19 by means of well designed randomized controlled trials.

Aims: To compare the effects of maternal subclinical hypothyroidism (SCH) diagnosed by the 2011 or 2017 “Guidelines of the American Thyroid Association (ATA) for the diagnosis and management of thyroid disease during pregnancy and the postpartum” during the first trimester on adverse pregnancy outcomes in thyroid peroxidase antibody (TPOAb)–negative pregnant women.Methods: There were 1,556 Chinese singleton pregnant women with negative TPOAb diagnosed with either SCH or euthyroidism who were investigated, and the prevalence and risk of obstetric outcomes were compared between the two groups using 2011 and 2017 ATA standards, respectively. The effects of a mildly elevated thyroid-stimulating hormone (TSH) concentration on adverse pregnancy outcomes were evaluated by binary logistic regression.Results: Maternal SCH identified by the 2011 ATA guidelines correlated with higher rates and risks of pregnancy-induced hypertension (PIH), preeclampsia, and low-birth-weight infants, while maternal SCH diagnosed by the 2017 ATA guidelines was more likely to develop PIH, preeclampsia, cesarean delivery, preterm delivery, placenta previa, and total adverse maternal and neonatal outcomes. Moreover, a mildly elevated TSH level was significantly associated with PIH after adjustment for confounding factors.Conclusions: Compared with the 2011 ATA guidelines, the 2017 ATA guidelines could be more applicable to Chinese pregnant women to screen the effects of SCH on the majority of adverse pregnancy outcomes.

Background. Recombinant tissue plasminogen activator (rtPA) is the only recommended pharmacological treatment for acute ischemic stroke, but it has a restricted therapeutic time window. When administered at time points greater than 4.5 h after stroke onset, rtPA disrupts the blood-brain barrier (BBB), which leads to serious brain edema and hemorrhagic transformation. Electroacupuncture (EA) exerts a neuroprotective effect on cerebral ischemia; however, researchers have not clearly determined whether EA increases the safety of thrombolysis and extends the therapeutic time window of rtPA administration following ischemic stroke. Objective. The present study was conducted to test the hypothesis that EA extends the therapeutic time window of rtPA for ischemic stroke in a male rat model of embolic stroke. Methods. SD rats were randomly divided into the sham operation group, model group, rtPA group, EA+rtPA group, and rtPA+MEK1/2 inhibitor group. An injection of rtPA was administered 6 h after ischemia. Rats were treated with EA at the Shuigou (GV26) and Neiguan (PC6) acupoints at 2 h after ischemia. Neurological function, infarct volume, BBB permeability, brain edema, and hemorrhagic transformation were assessed at 24 h after ischemia. Western blotting and immunofluorescence staining were performed to detect the levels of proteins involved in the ERK1/2 signaling pathway (MEK1/2 and ERK1/2), tight junction proteins (Claudin5 and ZO-1), and MMP9 in the ischemic penumbra at 24 h after stroke. Results. Delayed rtPA treatment aggravated hemorrhagic transformation and brain edema. However, treatment with EA plus rtPA significantly improved neurological function and reduced the infarct volume, hemorrhagic transformation, brain edema, and EB leakage in rats compared with rtPA alone. EA increased the levels of tight junction proteins, inhibited the activation of the ERK1/2 signaling pathway, and reduced MMP9 overexpression induced by delayed rtPA thrombolysis. Conclusions. EA potentially represents an effective adjunct method to increase the safety of thrombolytic therapy and extend the therapeutic time window of rtPA administration following ischemic stroke. This neuroprotective effect may be mediated by the inhibition of the ERK1/2-MMP9 pathway and alleviation of the destruction of the BBB.

AIM: To compare clinical effects and cost of panretinal photocoagulation(PRP)combined with Ranibizumab or triamcinolone acetonide(TA)for diabetic macular edema(DME). METHODS: Forty-eight patients(48 eyes)with DME and diabetic retinopathy(DR)receiving PRP were randomly assigned to two groups, which were respectively intravitreally injected ranibizumab(0.5mg)and TA(4mg). Ranibizumab(0.5mg)was intravitreal injected every 4wk for 3 times. The effects of injection for DME were evaluated using best-corrected visual acuity(BCVA), central macular thickness(CMT)and intraocular pressure(IOP). During the follow-up, other injections were performed to eyes which had CMT greater than 400μm. The medical costs were calculated at 12wk and 24wk. RESULTS: BCVA and CMT between 2 groups were not significantly different(P>0.05); BCVA and CMT among different time points were significantly different(PPPP=0.33). There was significant difference between the two groups at 12wk and 16wk on BCVA and that injected with ranibizumab was better(P=0.03, 0.045). CMT decreased in two groups at all the time after injection(PPCONCLUSION: Both PRP combined with ranibizumab or TA for DME can effectively control disease progression in short time. Therapeutic effect is not significant between two methods, but PRP combined with TA is more economic.

In the title organic salt, C17H20F2N3O3+·C8H4FO4−, proton transfer leads to one protonated lomefloxacin molecule (HLf+) and one 3-carboxy-5-fluorobenzoate (5-F-Hip−) anion in the asymmetric unit. The HLf+ cation is bent, with a dihedral angle of 38.3 (1)° between the quinoline ring and the piperazinium moiety. In the crystal, two kinds of N—H...O and O—H...O hydrogen-bonded chains cross-link each other to produce a three-dimensional network structure that is additionally stabilized by weak C—H...O and C—H...F hydrogen bonds, as well as π–π interactions. The methyl group attached to the piperazinium ring is disordered over two sets of sites [refined ratio: 0.645 (5):0.335 (5)], indicating the presence of both enantiomers of the cation in the structure.

Abstract Background Thyroglobulin measurement with fine-needle aspiration (Tg-FNA) is a sensitive method for detecting metastatic papillary thyroid carcinoma (PTC). However, the diagnostic threshold is not well established and the influence of the thyroid gland on the cutoff value is also controversial. In this study, patients were classified into two groups according to the presence or absence of thyroid tissue, to determine an appropriate cutoff value for clinical practice. Methods Patients with a history of thyroid nodules or surgery for PTC and with enlarged cervical lymph nodes on an FNA examination were enrolled for Tg-FNA detection. Results One hundred ninety-six lymph nodes (189 patients) were included: 100 from preoperative patients, 49 from patients treated with partial thyroid ablation, and 47 from patients with total thyroid ablation. In 149 lymph nodes from patient with thyroids, the cutoff value for Tg-FNA was 55.99 ng/mL (sensitivity, 95.1%; specificity, 100%), whereas in 47 lymph nodes from patients without a thyroid, it was 9.71 ng/mL (sensitivity, 96.7%; specificity, 100%). Thus, the cutoff value for Tg-FNA was higher in patients with thyroids than in patients without thyroids. Conclusions The cutoff value for Tg-FNA is influenced by residual thyroid tissue, and a higher cutoff value is recommended for patients with thyroids than for patients without thyroids.

The genus Cuscuta (Convolvulaceae) is an annual parasitic twining herb. There are about 200 species in this genus, which are widely distributed in tropical and subtropical areas. Cuscuta is mainly parasitic on crops bringing significant losses to the production of agriculture. Furthermore, dried seeds of C. chinensis and C. australis are used as a Chinese traditional herbal medicine. Despite the importance of Cuscuta species, it is difficult to distinguish these plants by the naked eye. Moreover, plastid sequence information available for Cuscuta species is limited. In this study, the complete chloroplast (cp) genome sequence of C. australis was determined using next-generation sequencing. The entire cp genome was determined to be 85,263 bp in length. It contained large single-copy (LSC) and small single-copy (SSC) regions of 50,384 and 6727 bp, respectively, which were separated by a pair of 14,076 bp inverted repeat (IR) regions. The genome contained 98 genes, including 61 protein-coding genes, 29 tRNA genes, and 4 rRNA genes. The overall GC content of the genome is 37.8%. A phylogenetic tree reconstructed by 26 chloroplast genomes reveals that C. australis is most related with Cuscuta pentagona in Convolvulaceae, with bootstrap support values of 100%.

We proposed a meta-atom design strategy that can achieve full complex-amplitude modulation based on analytical method for circularly polarized waves. The meta-atom can be regarded as two cascaded quarter wave plates, the orientation angles of which provide two degrees of freedom for obtaining arbitrary amplitude and phase modulation through accurate analytical method. As verification, a microwave meta-atom is designed and used to realize lateral and axial dual focusing. The proposed design strategy provides a straightforward route for full, continuous control of both amplitude and phase, and can stimulate various advanced meta-devices.

Background: Rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly prolonged event-free survival in first-line chemotherapy for patients with diffuse large B-cell lymphoma (DLBCL). But relapse and refractory DLBCL occur frequently. Although rituximab is effective, its role in salvage therapy after autologous transplant remains unclear. Maintenance therapy with rituximab in responding patients after first line chemotherapy may be a useful novel approach capable of eradicating minimal residual disease and to bring survival benefit. This systematic review and meta-analysis evaluated the effects of rituximab maintenance treatment and salvage therapy of patients with DLBCL. Methods: We performed a systematic review and meta-analysis of randomized controlled trials and compared rituximab maintenance or salvage therapy at relapse with observation. We searched the Cochrane Library, PubMed, EMBASE, conference proceedings, databases of ongoing trials, and references of published trials. Two reviewers independently assessed the quality of the trials and extracted data. Hazard ratios for time-to-event data were estimated and pooled. Results: Seven trials including 1470 DLBCL patients were included in this systematic review and meta-analysis. Patients treated with maintenance rituximab have better overall survival (OS) and event-free survival (EFS) than patients in the observation arm, but there was no statistical significance. Patients who received rituximab salvage therapy for relapse or refractory DLBCL have statistically significantly better OS [HR of death = 0.72, 95% CI (0.55-0.94), P = 0.02], progression-free survival (PFS) [HR = 0.61, 95% CI (0.52-0.72), P < 0.05], odds ratio (OR) [RR = 1.26, 95% CI (1.07-1.47), P = 0.004] than patients in the observation arm. The rate of infection-related adverse events was higher with rituximab treatment [RR = 1.37, 95% CI = (1.14 - 1.65) P =0.001]. Conclusions: After first-line chemotherapy, the two rituximab-combined treatment strategies, including maintenance and salvage therapies can bring survival benefit. But due to the few studies, the low methodological quality assessment and the low outcome evidence quality, it′s not confirmed that the two strategies are better than normal chemotherapy regimens. More high-quality randomized controlled trials are still needed to provide reliable evidence. The higher rate of infections after rituximab therapy should be taken into consideration when making treatment decisions.

Previous studies demonstrated that inflammatory microenvironment promoted prostate cancer progression. This study investigated whether total glucosides of paeony (TGP), the active constituents extracted from the root of Paeonia Lactiflora Pall, suppressed lipopolysaccharide (LPS)-stimulated proliferation, migration and invasion in androgen insensitive prostate cancer cells. PC-3 cells were incubated with LPS (2.0 μg/mL) in the absence or presence of TGP (312.5 μg /mL). As expected, cells at S phase and nuclear CyclinD1, the markers of cell proliferation, were increased in LPS-stimulated PC-3 cells. Migration activity, as determined by wound-healing assay and transwell migration assay, and invasion activity, as determined by transwell invasion assay, were elevated in LPS-stimulated PC-3 cells. Interestingly, TGP suppressed LPS-stimulated PC-3 cells proliferation. Moreover, TGP inhibited LPS-stimulated migration and invasion of PC-3 cells. Additional experiment showed that TGP inhibited activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK)/p38 in LPS-stimulated PC-3 cells. Correspondingly, TGP attenuated upregulation of interleukin (IL)-6 and IL-8 in LPS-stimulated PC-3 cells. In addition, TGP inhibited nuclear translocation of signal transducer and activator of transcription 3 (STAT3) in LPS-stimulated PC-3 cells. These results suggest that TGP inhibits inflammation-associated STAT3 activation and proliferation, migration and invasion in androgen insensitive prostate cancer cells.

The newly discovered Tiantangshan tin polymetallic deposit is located in the southeast Nanling Range, Cathaysia block, Southeast China. The tin orebodies are mainly hosted in the greisen and the fractured alteration zones of the tufflava and trachydacite. However, the genetic relationship between the hidden alkali-feldspar granite and volcanic rocks and the tin mineralization remains poorly understood. This paper presents SHRIMP zircon U−Pb dating, whole-rock major and trace element analyses, as well as Nd isotopic data of the trachydacite and alkali-feldspar granite. The SHRIMP zircon U−Pb dating of the alkali-feldspar granite and trachydacite yields weight mean 206Pb/238U ages of 138.4 ± 1.2, and 136.2 ± 1.2 Ma, respectively. These granitic rocks have high levels of SiO2 (64.2−75.4 wt%, mostly > 68 wt%), alkalis (K2O + Na2O > 8.3 wt%), REE (except for Eu), HFSE (Zr + Nb + Ce + Y > 350 ppm) and Ga/Al ratios (10,000 × Ga/Al > 2.6), suggesting that they belong to the A-type granite. According to the high Y/Nb and Yb/Ta ratios, they can be further classified into A1 subtype. Their εNd (T) range from −3.8 to −6.5. They were likely generated by the assimilation-fractional crystallization (AFC) of the coeval oceanic island basalts -like basaltic magma. This study suggests that the A1 type granite is also a potential candidate for the exploration of tin deposits.

Lenalidomide could effectively induce red blood cell (RBC) transfusion independence (TI) in patients with lower-risk (Low/Intermediate-1) myelodysplastic syndrome (MDS) with or without 5q deletion. However whether lenalidomide ultimately improves the overall survival (OS) of lower-risk MDS patients and reduces the progression to AML remains controversial.A meta-analysis was conducted to examine the efficacy and safety of lenalidomide in the treatment of lower-risk MDS. Efficacy was assessed according to erythroid hematologic response (HI-E), cytogenetic response (CyR), OS and AML progression. Safety was evaluated based on the occurrence rates of grades 3-4 adverse events (AEs).Seventeen studies were included consisting of a total of 2160 patients. The analysis indicated that the overall rate of HI-E was 58% with 95% confidence interval (CI) of 43-74%. The pooled estimates for the rates of CyR, complete CyR, and partial CyR were 44% (95% CI 19-68%), 21% (95% CI 13-30%) and 23% (95% CI 15-32%), respectively. The patients with 5q deletion had significantly higher rate of HI-E and CyR than those without 5q deletion (P = 0.002 and 0.001, respectively). The incidences of grades 3-4 neutropenia, thrombocytopenia, leukopenia, anemia, deep vein thrombosis, diarrhea, fatigue and rash were 51% (95% CI 30-73%), 31% (95% CI 20-42%), 9% (95% CI 5-13%), 7% (95% CI 2-12%), 3% (95% CI 2-5%), 3% (95% CI 1-5%), 2% (95% CI 1-4%) and 2% (95% CI 1-3%), respectively. Lenalidomide significantly improved OS (HR: 0.62, 95% CI 0.47-0.83, P = 0.001) and lowered the risk of AML progression in del(5q) patients (RR: 0.61, 95% CI 0.41-0.91, P = 0.014).In spite of the AEs, lenalidomide could be effectively and safely used for the treatment of lower-risk MDS patients with or without 5q deletion.

Three new 14,15-secopregnane-type glycosides, stauntosides UA, UA1, and UA2, were isolated from the roots of Cynanchum stauntonii. The three compounds share the first reported and same basic structural features of 3β-hydroxy-14:16,15:20,18:20-triepoxy-5α:9α-peroxy-14,15-secopregnane-6,8(14)-diene named as stauntogenin G as the aglycones. The structures of the new compounds were characterized on the basis of extensive spectroscopic analyses, mainly 1D and 2D NMR and MS methods and chemical analysis. The isolation and identification of the new compounds graced the structural diversity of pregnane-type steroids from C. stauntonii.

Acetaminophen (APAP) overdose is the most frequent cause of acute liver failure and is primarily caused by cytochrome P450 (CYP) 2E1-driven conversion of APAP into hepatotoxic metabolites. Several reports showed that melatonin attenuated APAP-induced acute liver failure. Nevertheless, the exact mechanism remains obscure. In the present study, we investigated the effects of melatonin on apoptosis-inducing factor (AIF)-dependent cell death in APAP-induced acute liver failure. Mice were intraperitoneally (i.p.) injected with different doses of melatonin (1.25, 5, 20 mg/kg) 30 min before APAP (300 mg/kg, i.p.). As expected, melatonin significantly alleviated APAP-induced cell death, as determined by TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay. Further analysis showed that melatonin significantly attenuated APAP-induced activation of the serine/threonine kinase receptor interacting protein 1 (RIP1). In addition, melatonin inhibited APAP-induced hepatic c-Jun N-terminal kinase (JNK) phosphorylation and mitochondrial Bax translocation. Correspondingly, melatonin inhibited APAP-induced translocation of AIF from mitochondria to nuclei. Interestingly, no changes were induced by melatonin on hepatic CYP2E1 expression. In addition, melatonin had little effect on APAP-induced hepatic glutathione (GSH) depletion. In conclusion, melatonin protects against AIF-dependent cell death during APAP-induced acute liver failure through its direct inhibition of hepatic RIP1 and subsequent JNK phosphorylation and mitochondrial Bax translocation.

The synthesis of cyclic carbonates through cycloaddition reactions between epoxides and carbon dioxide (CO2) is an important industrial process. Metal-Organic Frameworks (MOFs) have functional and ordered pore structures, making them attractive catalysts for converting gas molecules into valuable products. One approach to enhance the catalytic activity of MOFs in CO2 cycloaddition reactions is to create open metal sites within MOFs. In this study, the amino-functionalized rare earth Gd-MOF (Gd-TPTC-NH2) and its ionic liquid composite catalysts (Gd-TPTC-NH-[BMIM]Br) were synthesized using 2'-amino-[1,1':4',1"-terphenyl]-3,3",5,5"-tetracarboxylic acid (H4TPTC-NH2) as the ligand. The catalytic performance of these two catalysts was observed in the cycloaddition reaction of CO2 and epoxides. Under the optimized reaction conditions, Gd-TPTC-NH-[BMIM]Br can effectively catalyze the cycloaddition reaction of a variety of epoxide substrates with good to excellent yields of cyclic carbonate products. Comparatively, epichlorohydrin and epibromohydrin, which possess halogen substituents, promote higher yields of cyclic carbonates due to the electron-withdrawing nature of Cl and Br substituents. Additionally, the Gd-TPTC-NH- [BMIM]Br catalyst demonstrated good recyclability and reproducibility, maintaining its catalytic activity without any changes in its structure or properties after five reuse cycles. [ABSTRACT FROM AUTHOR]