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This paper provides a historical, religious-philosophical context for the study of the Daoist text known as The Secret of the Golden Flower. An updated study is conducted into the controversy over the source of the text including the editions translated by Richard Wilhelm and Thomas Cleary. The main teachings of the text and the basics of two major denominations of Daoism are introduced to ground later critiques of Jung's commentary. The psychodynamics of analytical psychology, especially those concerned with integration of unconscious contents and the realization of the self (individuation) are compared with the psycho-spiritual dynamics of integration in Eastern spirituality based on the Golden Flower text. The paper concludes that it was amiss for Jung to have equated the Western 'unconscious' with states of higher consciousness in Eastern meditation practices, although his claim that Eastern higher consciousness is characterized by a nebulous state of non-intentionality does raise questions about the appropriateness of calling Eastern meditative states 'consciousness'. A new concept is required to characterize the special qualities of this psychic state shared generally by Eastern spiritual traditions and a more meaningful comparison may be found in Jung's concept of the self. [ABSTRACT FROM AUTHOR]

This article draws on a survey of internal migrant workers in China's Jiangsu province to shed light on the characteristics of migrant workers who receive social insurance and explain why some migrants take up social insurance while others do not. Of the factors which potentially explain which migrants receive social insurance, gender, past earnings, ties to the city to which the migrant had moved, the ownership type of the enterprise in which the migrant works and residential registration status are all found to be statistically significant predictors. The article concludes with the suggestion that the high level of scepticism with respect to social protection that has been reported as being manifest among migrants is justified. There is little likelihood the majority of migrant workers who have moved to China's towns and cities will be able to access the social insurance benefits traditionally available to those with urban registration. [ABSTRACT FROM AUTHOR]

The objective of this preclinical study was to evaluate the feasibility and safety of transcatheter endocardial alginate hydrogel injection (TEAi) in a large animal model, utilizing the high-stiffness XDROP® alginate hydrogel in combination with the dedicated EndoWings® catheter-based system. All swine (n = 9) successfully underwent TEAi without complications. Acute results from a subset of animals (n = 5) demonstrated the ability of the catheter to access a wide range of endomyocardial areas and achieve consecutive circumferential hydrogel distribution patterns within the mid-left ventricular wall. Histological examinations at 6 months (n = 4) demonstrated that the XDROP® remained localized within the cardiac tissue. In addition, serial echocardiographic imaging showed that XDROP® had no adverse impacts on LV systolic and diastolic functions. In conclusion, this innovative combination technology has the potential to overcome the translational barriers related to alginate hydrogel delivery to the myocardium., (© 2024. The Author(s).)

Waterborne polyurethanes (WPUs) have attracted great interest owing to their environmentally friendly properties, and are wildly applied in production and daily life. However, waterborne polyurethanes are flammable. Up to now, the challenge remains to prepare WPUs with excellent flame resistance, high emulsion stability, and outstanding mechanical properties. Herein, a novel flame-retardant additive, 2-hydroxyethan-1-aminium (2-(1H-benzo[d]imidazol-2-yl)ethyl)(phenyl)phosphinate (BIEP-ETA) has been synthesized and applied to improve the flame resistance of WPUs, which has both phosphorus nitrogen synergistic effect and the ability to form hydrogen bonds with WPUs. The WPU blends (WPU/FRs) exhibited a positive fire-retardant effect in both the vapor and condensed phases, with significantly improved self-extinguishing performance and reduced heat release value. Interestingly, thanks to the good compatibility between BIEP-ETA and WPUs, WPU/FRs not only have higher emulsion stability, but also have better mechanical properties with synchronously improved tensile strength and toughness. Moreover, WPU/FRs also exhibit excellent potential as a corrosion-resistant coating.

Background: The effect of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) on mortality was preliminarily explored through the comparison of ACEIs/ARBs with non-ACEIs/ARBs in patients with coronavirus disease 2019 (COVID-19). Reaching a conclusion on whether previous ACEI/ARB treatment should be continued in view of the different ACE2 levels in the comparison groups was not unimpeachable. Therefore, this study aimed to further elucidate the effect of ACEI/ARB continuation on hospital mortality, intensive care unit (ICU) admission, and invasive mechanical ventilation (IMV) in the same patient population., Methods: We searched PubMed, the Cochrane Library, Ovid, and Embase for relevant articles published between December 1, 2019 and April 30, 2022. Continuation of ACEI/ARB use after hospitalization due to COVID-19 was considered as an exposure and discontinuation of ACEI/ARB considered as a control. The primary outcome was hospital mortality, and the secondary outcomes included 30-day mortality, rate of ICU admission, IMV, and other clinical outcomes., Results: Seven observational studies and four randomized controlled trials involving 2823 patients were included. The pooled hospital mortality in the continuation group (13.04%, 158/1212) was significantly lower than that (22.15%, 278/1255) in the discontinuation group (risk ratio [RR] = 0.45; 95% confidence interval [CI], 0.28-0.72; P = 0.001). Continuation of ACEI/ARB use was associated with lower rates of ICU admission (10.5% versus 16.2%, RR = 0.63; 95% CI 0.5-0.79; P < 0.0001) and IMV (8.2% versus 12.5%, RR = 0.62; 95% CI 0.46-0.83, P = 0.001). Nevertheless, the effect was mainly demonstrated in the observational study subgroup (P < 0.05). Continuing ACEI/ARB had no significant effect on 30-day mortality (P = 0.34), acute myocardial infarction (P = 0.08), heart failure (P = 0.82), and acute kidney injury after hospitalization (P = 0.98)., Conclusion: Previous ACEI/ARB treatment could be continued since it was associated with lower hospital deaths, ICU admission, and IMV in patients with COVID-19, although the benefits of continuing use were mainly shown in observational studies. More evidence from multicenter RCTs are still needed to increase the robustness of the data. Trial registration PROSPERO (CRD42022341169). Registered 27 June 2022., (© 2023. The Author(s).)

A convenient and efficient tandem cyclization/sulfenylation of o -alkynyl-phenols/-anilines/enaminones for the synthesis of diverse sulfur-containing bisheterocycles has been developed using stable, odorless, and easy-to-handle elemental S 8 as a building block under green chemistry conditions. Notably, a one-step simple base-mediated organic transformation affords a benzofuran (indole or chromone) ring and two C-S bonds. Attractive features of this methodology include the absence of a metal catalyst, mild conditions, good functional group tolerance, and valuable product structures.

Pulmonary hypertension (PH) is a type of clinical pathophysiological syndrome characterized by a progressive increase in pulmonary vascular resistance and subsequent progressive failure of the right heart function, and is a common complication of many diseases. Mesenchymal stem cells (MSCs) autonomously home to sites damaged by disease, repair damaged tissues, and participate in the regulation of systemic inflammation and immune responses, which have good clinical application prospects. Extracellular vesicles (EVs), such as exosomes and microvesicles, participate in various biological activities by regulating intercellular communication. Exosomes secreted into the extracellular environment also affect the host immune system. MSC-derived extracellular vesicles (MSC-EVs), as a mediator in the paracrine processes of MSCs, carry biologically active substances such as proteins, lipids, mRNA, and micro-RNA. MSC-EVs therapies, safer than cell-based treatments, have been shown to be effective in modulating macrophages to support anti-inflammatory phenotypes, which are strongly related to histological and functional benefits in preclinical models of pulmonary hypertension. The main effects of active substances and their potential medical value have attracted wide attention from researchers. This article reviews the role and relevant mechanisms of MSC-EVs in the treatment of pulmonary hypertension in recent studies and provides a basis for their future clinical applications., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Ji-Hong Xu et al.)

Acute pancreatitis (AP) is a common serious acute condition of the digestive system that remains a clinical challenge. Severe acute pancreatitis (SAP) in particular is characterized by high morbidity and mortality. The present study was designed to investigate the protective effect of Galangin (Gal), a natural flavonol obtained from lesser galangal, on L-arginine-induced SAP in mice and in AR42J cells. Amylase and lipase activities were measured and the histopathology of the pancreas, lung, and kidney was evaluated. Inflammation and oxidative stress were assessed using ELISA, western blotting, RT-PCR, and immunohistochemistry. Gal was shown to reduce proinflammatory cytokine production and reactive oxygen species (ROS) generation in vivo and in vitro. L-arginine treatment reduced the expression of components of the nuclear factor E2-related factor 2 (Nrf2) signaling pathway and the downstream protein heme oxygenase-1 (HO-1) in mice, whereas Gal increased their expression. Furthermore, the Nrf2/HO-1 pathway inhibitor brusatol prevented the anti-inflammatory and antioxidant effects of Gal in mice with SAP. Taken together, our results imply that Gal has protective effects in L-arginine-induced SAP that are induced by the upregulation of the Nrf2/HO-1 pathway, which has anti-inflammatory and antioxidant effects. Thus, Gal may represent a promising treatment for SAP., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: To investigate the types and frequencies of thalassemia genes carried by the pregnant women in Guilin, Guangxi Zhuang Autonomous Region, China., Methods: From January 2015 to December 2019, blood samples of the pregnant women who visited the Outpatients of Obstetrics clinic and Eugenics Genetic clinic in Affiliated Hospital of Guilin Medical University were collected. Gap-PCR was used to detect deletional α-thalassemia, PCR-RDB to detect the gene mutations of non-deletional α-thalassemia and β-thalassemia, and MLPA or DNA sequencing to detect rare thalassemia mutations. Different types and frequencies of thalassemia mutations carried by pregnant women were analyzed statistically., Results: A total of 19 482 blood samples were collected, including 3 801 thalassemia gene carriers (19.51%). Seven types of α-thalassemia gene mutation were detected with a carrier rate of 15.43%. Among them, -- SEA deletion (7.32%), -α 3.7 deletion (3.97%), and -α 4.2 deletion (1.4%) were the commonest types. Twelve types of β-thalassemia mutations were detected with a carrier rate of 5.02%. Among them, CD41-42 (-TCTT) (2.32%), CD17 (AAG>TAG) (1.23%), and IVS-II-654 (C>T) (0.55%) were the commonest types. In addition, 107 cases of rare thalassemia gene mutations and abnormal hemoglobin were found at the same time., Conclusion: Guilin is a high-risk area for thalassemia. Alpha-thalassemia is dominated by -- SEA deletion, -α 3.7 deletion, and -α 4.2 deletion, while β-thalassemia is by CD41-42 (-TCTT), CD17(AAG>TAG), and IVS-II-654(C>T).

Background: Acute lung injury (ALI) is a common and life-threatening complication of severe acute pancreatitis (SAP). There are currently limited effective treatment options for SAP and associated ALI. Calycosin (Cal), a bioactive constituent extracted from the medicinal herb Radix Astragali exhibits potent anti-inflammatory properties, but its effect on SAP and associated ALI has yet to be determined., Aim: To identify the roles of Cal in SAP-ALI and the underlying mechanism., Methods: SAP was induced via two intraperitoneal injections of L-arg (4 g/kg) and Cal (25 or 50 mg/kg) were injected 1 h prior to the first L-arg challenge. Mice were sacrificed 72 h after the induction of SAP and associated ALI was examined histologically and biochemically. An in vitro model of lipopolysaccharide (LPS)-induced ALI was established using A549 cells. Immunofluorescence analysis and western blot were evaluated in cells. Molecular docking analyses were conducted to examine the interaction of Cal with HMGB1., Results: Cal treatment substantially reduced the serum amylase levels and alleviated histopathological injury associated with SAP and ALI. Neutrophil infiltration and lung tissue levels of neutrophil mediator myeloperoxidase were reduced in line with protective effects of Cal against ALI in SAP. Cal treatment also attenuated the serum levels and mRNA expression of pro-inflammatory cytokines tumor necrosis factor-α, interleukin-6, IL-1β, HMGB1 and chemokine (CXC motif) ligand 1 in lung tissue. Immunofluorescence and western blot analyses showed that Cal treatment markedly suppressed the expression of HMGB1 and phosphorylated nuclear factor-kappa B (NF-κB) p65 in lung tissues and an in vitro model of LPS-induced ALI in A549 cells suggesting a role for HGMB1 in the pathogenesis of ALI. Furthermore, molecular docking analysis provided evidence for the direct interaction of Cal with HGMB1., Conclusion: Cal protects mice against L-arg-induced SAP and associated ALI by attenuating local and systemic neutrophil infiltration and inflammatory response via inhibition of HGMB1 and the NF-κB signaling pathway., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Acute pancreatitis (AP) is an inflammatory disease in which the regulatory pathway is complex and not well understood. Soluble suppression of tumorigenicity 2 (sST2) protein receptor functions as a decoy receptor for interleukin (IL)-33 to prevent IL-33/suppression of tumorigenicity 2L (ST2L)-pathway-mediated T helper (Th)2 immune responses., Aim: To investigate the role of sST2 in AP., Methods: We assessed the association between sST2 and severity of AP in 123 patients enrolled in this study. The serum levels of sST2, C-reactive protein (CRP) and Th1- and Th2-related cytokines, including interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-2, IL-4, IL-5 and IL-13, were measured by highly sensitive ELISA, and the severity of AP in patients was evaluated by the 2012 Atlanta Classification Criteria., Results: Serum sST2 levels were significantly increased in AP patients, and further, these levels were significantly elevated in severe AP (SAP) patients compared to moderately severe AP (MSAP) and mild AP (MAP) patients. Logistic regression showed sST2 was a predictor of SAP [odds ratio (OR): 1.003 (1.001-1.006), P = 0.000]. sST2 cutoff point was 1190 pg/mL, and sST2 above this cutoff was associated with SAP. sST2 was also a predictor of any organ failure and mortality during AP [OR: 1.006 (1.003-1.009), P = 0.000, OR: 1.002 (1.001-1.004), P = 0.012, respectively]. Additionally, the Th1-related cytokines IFN-γ and TNF-α in the SAP group were higher and the Th2-related cytokine IL-4 in the SAP group was significantly lower than those in MSAP and MAP groups., Conclusion: sST2 may be used as a novel inflammatory marker in predicting AP severity and may regulate the function and differentiation of IL-33/ST2-mediated Th1 and Th2 Lymphocytes in AP homeostasis., Competing Interests: Conflict-of-interest statement: All the authors have no potential conflict of interest to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Liver injury is one of the most common complications during sepsis. Macrophage migration inhibitory factor (MIF) is an important proinflammatory cytokine. This study explored the role of MIF in the lipopolysaccharide (LPS)-induced liver injury through genetically manipulated mouse strains., Methods: The model of LPS-induced liver injury was established in wild-type and Mif-knockout C57/BL6 mice. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBil) were detected, and the expressions of MIF, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured. Liver histopathology was conducted to assess liver injury. Moreover, the inhibitions of MIF with (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) and 4-iodo-6-phenylpyrimidine (4-IPP) were used to evaluate their therapeutic potential of liver injury., Results: Compared with wild-type mice, the liver function indices and inflammation factors presented no significant difference in the Mif -/- mice. After 72 h of the LPS-induced liver injury, serum levels of ALT, AST, and TBil as well as TNF-α and IL-1β were significantly increased, but the knockout of Mif attenuated liver injury and inflammatory response. In liver tissue, mRNA levels of TNF-α, IL-1β and NF-κB p65 were remarkably elevated in LPS-induced liver injury, while the knockout of Mif reduced these levels. Moreover, in LPS-induced liver injury, the inhibitions of MIF with ISO-1 and 4-IPP alleviated liver injury and slightly attenuated inflammatory response. Importantly, compared to mice with LPS-induced liver injury, Mif knockout or MIF inhibitions significantly prolonged the survival of the mice., Conclusions: In LPS-induced liver injury, the knockout of Mif or MIF inhibitions alleviated liver injury and slightly attenuated inflammatory response, thereby prolonged the survival of the mice. Targeting MIF may be an important strategy to protect the liver from injury during sepsis., (Copyright © 2021. Published by Elsevier B.V.)

Objective: To observe the effects of electroacupuncture (EA) on the body weight, disease progression and the expression of heat shock protein 70 (HSP70) in lumbar spinal cord of amyotrophic lateral sclerosis (ALS) mice, so as to explore the mechanism of EA on treating ALS., Methods: Eighteen ALS transgenic SOD1 G93A mice were randomly divided into model, EA and medication groups, with 6 mice in each group, and six C57BL/6J mice were used as the normal group. Mice in the EA group received EA at "Quchi"(LI11)-"Hegu"(LI4), "Zusanli"(ST36)- "Sanyinjiao"(SP6), 30 min/time, 5 times/week, for 8 weeks.Mice in the medication group were given riluzole solution (7.6 mg·kg -1 ·d -1 ) by gavage for 8 weeks. The body weight of the mice was recorded and the motor function of the hind limbs was evaluated by the neurological function scoring stan-dard of the ALS Therapeutic Development Institute. The expression of HSP70 in lumbar spinal cord was detected by Western blot and immunohistochemistry, respectively., Results: Compared with the normal group, the body weight and the expression of HSP70 in the model group decreased significantly ( P <0.05), while no significant difference in the body weight was found among other groups( P >0.05). After intervention and in comparison with the model group, the disease onset time and paralysis time of the EA group and the medication group were significantly delayed ( P <0.05, P <0.01), the expression of HSP70 in the EA group and the medicine group was significantly increased ( P <0.05, P <0.01).But there was no significant difference in the survival time among all groups(P＞0.05). The disease onset time of the EA group was shorter than that in the medication group ( P <0.05)., Conclusion: EA can increase the expression of HSP70 in lumbar spinal cord, thereby delaying the progression of ALS.

The combination of transition-metal catalysis and organocatalysis increasingly offers chemists opportunities to realize diverse unprecedented chemical transformations. By combining iridium with chiral thiourea catalysis, direct enantioselective reductive cyanation and phosphonylation of secondary amides have been accomplished for the first time for the synthesis of enantioenriched chiral α-aminonitriles and α-aminophosphonates. The protocol is highly efficient and enantioselective, providing a novel route to the synthesis of optically active α-functionalized amines from the simple, readily available feedstocks. In addition, the reactions are scalable and the thiourea catalyst can be recycled and reused., (© 2021 Wiley-VCH GmbH.)

Objective: To evaluate the safety and efficacy of transcatheter aortic valve replacement (TAVR) with domestic prostheses in patients with severely stenotic bicuspid aortic valve (BAV). Methods: This study was a prospective single-center non-randomized controlled study. Patients with symptomatic severe aortic stenosis (AS), who underwent TAVR with domestic prostheses at the First Affiliated Hospital of Air Force Medical University from January 2016 to April 2020 were consecutively included in our study. Patients were divided into BAV group and tricuspid aortic valve (TAV) group according to the aortic valve morphology. Baseline characteristics, procedural outcomes were compared between the two groups, and the primary endpoint was one-month all-cause mortality. Results: A total of 100 patients aged (69.8±8.9) years were enrolled, including 71 (71%) males. There were 51 cases in BAV group and 49 cases in TAV group. Compared with TAV group, patient in the BAV group was younger ((67.1±8.6) years vs. (72.7±8.4) years, P =0.002) and had larger ascending aortic diameter at proximal part ((39.7±5.7) mm vs. (36.0±4.2) mm, P <0.001), lower Society of Thoracic Surgeons-Predicted Risk of Mortality (STS-PROM) score (3.1 (1.9, 5.4) % vs. 5.9 (2.6, 12.3) %, P= 0.002). In BAV group and TAV group, the incidence of 2nd prosthesis implantation was 15.7% (8/51) and 18.4% (9/49) ( P =0.721), the incidence of moderate or severe paravalvular regurgitation was 2.0% (1/51) and 0 ( P =1.000), the rate of device success was 82.4% (42/51) and 81.6% (40/49) ( P =0.925), respectively. One-month all-cause mortality was 2.0% (1/51) and 10.2% (5/49) ( P =0.108), respectively. Echocardiography showed that postprocedural mean pressure gradient (PGmean) was higher in the BAV group (13.0 (10.0, 16.0) mmHg vs. 9.0 (7.0, 14.0) mmHg, P =0.003) (1 mmHg=0.133 kPa), but the PGmean decrease post procedure as compared with that before TAVR was similar between the two groups ((36.7±16.6) mmHg vs. (36.2±17.5) mmHg, P =0.893). Conclusion: Favorable safety and efficacy are evidenced in patients with severely stenotic BAV undergoing TAVR with domestic prostheses.

Structurally similar analogues of given query compounds can be rapidly retrieved from chemical databases by the molecular similarity search approaches. However, the computational cost associated with the exhaustive similarity search of a large compound database will be quite high. Although the latest indexing algorithms can greatly speed up the search process, they cannot be readily applicable to molecular similarity search problems due to the lack of Tanimoto similarity metric implementation. In this paper, we first implement Python or C++ codes to enable the Tanimoto similarity search via several recent indexing algorithms, such as Hnsw and Onng. Moreover, there are increasing interests in computational communities to develop robust benchmarking systems to access the performance of various computational algorithms. Here, we provide a benchmark to evaluate the molecular similarity searching performance of these recent indexing algorithms. To avoid the potential package dependency issues, two separate benchmarks are built based on currently popular container technologies, Docker and Singularity. The Singularity container is a rather new container framework specifically designed for the high-performance computing (HPC) platform and does not need the privileged permissions or the separated daemon process. Both benchmarking methods are extensible to incorporate other new indexing algorithms, benchmarking data sets, and different customized parameter settings. Our results demonstrate that the graph-based methods, such as Hnsw and Onng, consistently achieve the best trade-off between searching effectiveness and searching efficiencies. The source code of the entire benchmark systems can be downloaded from https://github.uconn.edu/mldrugdiscovery/MssBenchmark.

We study the generation and propagation of hyperbolic secant solitons, Peregrine solitons, and various breathers in a coherently prepared three-level atomic system, where two lower states are coherently prepared prior to the injection of a strong pump field and a weak probe field. We show that a flat dispersion without gain and loss along with a large Kerr nonlinearity can be achieved in a broad range of probe field frequency. Moreover, optical hyperbolic secant solitons can be easily achieved in such a broad range at a very low light intensity and propagate stably. Due to the enhanced Kerr nonlinearity, we also show that it is possible to generate optical rogue waves and breathers with very weak light stimulus, which is three orders of magnitude smaller than that used in nonlinear fibers. Because the gain/absorption is negligible and the quantum noise of the probe field can be significantly suppressed, our work may pave the way for realizing solitons, rogue waves, and breathers at the quantum level.

The pyroptosis is a causative agent of rheumatoid arthritis, a systemic autoimmune disease merged with degenerative articular cartilage. Nevertheless, the precise mechanism of extracellular acidosis on chondrocyte pyroptosis is largely unclear. Acid-sensing ion channels (ASICs) belong to an extracellular H + -activated cation channel family. Accumulating evidence has highlighted activation of ASICs induced by extracellular acidosis upregulate calpain and calcineurin expression in arthritis. In the present study, to investigate the expression and the role of acid-sensing ion channel 1a (ASIC1a), calpain, calcineurin, and NLRP3 inflammasome proteins in regulating acid-induced articular chondrocyte pyroptosis, primary rat articular chondrocytes were subjected to different pH, different time, and different treatments with or without ASIC1a, calpain-2, and calcineurin, respectively. Initially, the research results showed that extracellular acidosis-induced the protein expression of ASIC1a in a pH- and time-dependent manner, and the messenger RNA and protein expressions of calpain, calcineurin, NLRP3, apoptosis-associated speck-like protein, and caspase-1 were significantly increased in a time-dependent manner. Furthermore, the inhibition of ASIC1a, calpain-2, or calcineurin, respectively, could decrease the cell death accompanied with the decreased interleukin-1β level, and the decreased expression of ASIC1a, calpain-2, calcineurin, and NLRP3 inflammasome proteins. Taken together, these results indicated the activation of ASIC1a induced by extracellular acidosis could trigger pyroptosis of rat articular chondrocytes, the mechanism of which might partly be involved with the activation of calpain-2/calcineurin pathway., (© 2020 International Federation for Cell Biology.)

Nϵ-carboxymethyl-lysine (CML), an advanced glycation end product, is involved in vascular calcification (VC) in diabetic atherosclerosis. This study aimed to investigate the effects of CML on VC in diabetic atherosclerosis induced by vascular smooth muscle cell (VSMC)-derived foam cells. Human studies, animal studies and cell studies were performed. The human study results from 100 patients revealed a poor blood glucose and lipid status and more severe coronary lesions and stenosis in patients with coronary artery disease and diabetes mellitus. Intraperitoneal injection of streptozotocin combined with a high-fat diet was used to build a diabetic atherosclerosis model in ApoE -/- mice. The animal study results indicated that CML accelerated VC progression in diabetic atherosclerosis by accelerating the accumulation of VSMC-derived foam cells in ApoE -/- mice. The cell study results illustrated that CML induced VSMC-derived foam cells apoptosis and aggravated foam cells calcification. Consistent with this finding, calcium content and the expression levels of alkaline phosphatase, bone morphogenetic protein 2 and runt-related transcription factor 2 were significantly elevated in A7r5 cells treated with oxidation-low-density lipoprotein and CML. Thus, we concluded that CML promoted VSMC-derived foam cells calcification to aggravate VC in diabetic atherosclerosis, providing evidence for the contribution of foam cells to diabetic VC., (Copyright © 2020 Xu, Zhou, Zhu, Qin, Zhu, Zhang, Li, Xing, Lian, Li, Sun, Wang, Zhang and Cao.)

Epidemiological evidence suggests that the etiology and pathogenesis of rheumatoid arthritis (RA) are closely associated with estrogen metabolism and deficiency. Estrogen protects against articular damage. Estradiol replacement therapy ameliorates local inflammation and knee joint swelling in ovariectomized models of RA. The mechanistic basis for the protective role of 17β-estradiol (17β-E2) is poorly understood. Acid-sensing ion channel 1a (ASIC1a), a sodium-permeable channel, plays a pivotal role in acid-induced articular chondrocyte injury. The aims of this study were to evaluate the role of 17β-E2 in acid-induced chondrocyte injury and to determine the effect of 17β-E2 on the level and activity of ASIC1a protein. Results showed that pretreatment with 17β-E2 attenuated acid-induced damage, suppressed apoptosis, and restored mitochondrial function. Further, 17β-E2 was shown to reduce protein levels of ASIC1a through the ERα receptor, to protect chondrocytes from acid-induced apoptosis, and to induce ASIC1a protein degradation through the autophagy-lysosomal pathway. Taken together, these results show that the use of 17β-E2 may be a novel strategy for the treatment of RA by reducing cartilage destruction through down-regulation of ASIC1a protein levels., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We theoretically investigate the quantum phase transition in the collective systems of qubits in a high quality cavity, where the cavity field is squeezed via the optical parametric amplification process. We show that the squeezed light induced symmetry breaking can result in quantum phase transition without the ultrastrong coupling requirement. Using the standard mean field theory, we derive the condition of the quantum phase transition. Surprisingly, we show that there exists a tricritical point where the first- and second-order phase transitions meet. With specific atom-cavity coupling strengths, both the first- and second-order phase transition can be controlled by the nonlinear gain coefficient, which is sensitive to the pump field. These features also lead to an optical switching from the normal phase to the superradiant phase by just increasing the pump field intensity. The signature of these phase transitions can be observed by detecting the phase space Wigner function distribution with different profiles controlled by the squeezed light intensity. Such superradiant phase transition can be implemented in various quantum systems, including atoms, quantum dots, and ions in optical cavities as well as the circuit quantum electrodynamics system.

To clarify foam cell origination in atherosclerosis, a series of morphologic and ultrastructural alterations of vascular smooth muscle cells (VSMCs) and foam cells were studied by light and electron microscopy in atherosclerotic aortas from hyperlipidemic rabbits induced for 5 weeks. The study exhibited that VSMCs were severely degenerated and damaged, including irregular shapes, expanded mitochondria, aplenty lipid droplets, and disarranged myofilaments in cytoplasm in media adjacent to atheromatic bottoms. Most lipid laden cells shared interphase structures of VSMCs and foam cells, and some dissolved spindle cells contained lipid droplets, lipofuscin, and rod-like CCs in cytoplasm also. The result demonstrated that VSMCs were degenerated and transformed into foam cells in atherosclerosis, which was responsible for the accumulation of lipid and cholesterol crystals in atherosclerotic arteries.

The conversion of skeletal muscle fiber from fast twitch to slow-twitch is important for sustained and tonic contractile events, maintenance of energy homeostasis, and the alleviation of fatigue. Skeletal muscle remodeling is effectively induced by endurance or aerobic exercise, which also generates several tricarboxylic acid (TCA) cycle intermediates, including succinate. However, whether succinate regulates muscle fiber-type transitions remains unclear. Here, we found that dietary succinate supplementation increased endurance exercise ability, myosin heavy chain I expression, aerobic enzyme activity, oxygen consumption, and mitochondrial biogenesis in mouse skeletal muscle. By contrast, succinate decreased lactate dehydrogenase activity, lactate production, and myosin heavy chain IIb expression. Further, by using pharmacological or genetic loss-of-function models generated by phospholipase Cβ antagonists, SUNCR1 global knockout, or SUNCR1 gastrocnemius-specific knockdown, we found that the effects of succinate on skeletal muscle fiber-type remodeling are mediated by SUNCR1 and its downstream calcium/NFAT signaling pathway. In summary, our results demonstrate succinate induces transition of skeletal muscle fiber via SUNCR1 signaling pathway. These findings suggest the potential beneficial use of succinate-based compounds in both athletic and sedentary populations., (© 2019 The Authors. Published under the terms of the CC BY 4.0 license.)

We consider the problem of clustering graph nodes over large-scale dynamic graphs, such as citation networks, images and web networks, when graph updates such as node/edge insertions/deletions are observed distributively. We propose communication-efficient algorithms for two well-established communication models namely the message passing and the blackboard models. Given a graph with n nodes that is observed at s remote sites over time [1, t ], the two proposed algorithms have communication costs Õ ( ns ) and Õ ( n + s ) ( Õ hides a polylogarithmic factor), almost matching their lower bounds, Ω( ns ) and Ω ( n + s ), respectively, in the message passing and the blackboard models. More importantly, we prove that at each time point in [1, t ] our algorithms generate clustering quality nearly as good as that of centralizing all updates up to that time and then applying a standard centralized clustering algorithm. We conducted extensive experiments on both synthetic and real-life datasets which confirmed the communication efficiency of our approach over baseline algorithms while achieving comparable clustering results.

Graph sparsification has been used to improve the computational cost of learning over graphs, e.g. , Laplacian-regularized estimation, graph semisupervised learning ( SSL ) and spectral clustering ( SC ). However, when graphs vary over time, repeated sparsification requires polynomial order computational cost per update. We propose a new type of graph sparsification namely fault-tolerant ( FT ) sparsification to significantly reduce the cost to only a constant. Then the computational cost of subsequent graph learning tasks can be significantly improved with limited loss in their accuracy. In particular, we give theoretical analysis to upper bound the loss in the accuracy of the subsequent Laplacian-regularized estimation, graph SSL and SC , due to the FT sparsification. In addition, FT spectral sparsification can be generalized to FT cut sparsification, for cut-based graph learning. Extensive experiments have confirmed the computational efficiencies and accuracies of the proposed methods for learning on dynamic graphs.

We investigate a single atom cavity-QED system directly driven by a broadband squeezed light. We demonstrate how the squeezed radiation can be used to sense the presence of a single atom in a cavity. This happens by transferring one of the photons from the field in a state with an even number of photons to the atom and thereby populating an odd number of Fock states. Specifically, the presence of the atom is sensed by remarkable changing in the presence of one photon and the loss of squeezing of the cavity field. A complete study of quantum fluctuations and the excitation of multiphoton transitions is given.

The VC-dimension, which has wide uses in learning theory, has been used in the analysis and design of graph algorithms recently. In this paper, we study the problem of bounding the VC-dimension of unique round-trip shortest path set systems ( URTSP ), which are set systems induced by sets of vertices in unique round-trip shortest paths in directed graphs. We first show that different from the VC-dimensions of set systems induced by unique undirected and directed shortest paths in undirected and directed graphs respectively, the VC-dimension of URTSP can be larger than 3. We then prove that the VC-dimension of URTSP is at most 32. Furthermore, we apply the VC-dimension result to the minimum k -round-trip shortest path cover problem ( k-RTSPC ), which is to find for a directed graph a minimum vertex set to intersect every round-trip shortest path containing at least k vertices, and derive an upper bound on the size of the vertex set. The k-RTSPC problem can be useful in many real-world applications, including optimal placement of facilities.

Antagonism between heavy metal and selenium (Se) could significantly affect their biotoxicity, but little is known about the mechanisms underlying such microbial-mediated antagonistic processes as well as the formed products. In this work, we examined the cadmium (Cd)-Se interactions and their fates in Caenorhabditis elegans through in vivo and in vitro analysis and elucidated the machinery of Se-stimulated Cd detoxification. Although the Se introduction induced up to 3-fold higher bioaccumulation of Cd in C. elegans than the Cd-only group, the nematode viability remained at a similar level to the Cd-only group. The relatively lower level of reactive oxygen species in the Se & Cd group confirms a significantly enhanced Cd detoxification by Se. The Cd-Se interaction, mediated by multiple thiols, including glutathione and phytochelatin, resulted in the formation of less toxic cadmium selenide (CdSe)/cadmium sulfide (CdS) nanoparticles. The CdSe/CdS nanoparticles were mainly distributed in the pharynx and intestine of the nematodes, and continuously excreted from the body, which also benefitted the C. elegans survival. Our findings shed new light on the microbial-mediated Cd-Se interactions and may facilitate an improved understanding and control of Cd biotoxicity in complicated coexposure environments.

Vacuum sealing drainage (VSD) is frequently used in abdominal surgeries. However, relevant guidelines are rare. Chinese Trauma Surgeon Association organized a committee composed of 28 experts across China in July 2017, aiming to provide an evidence-based recommendation for the application of VSD in abdominal surgeries. Eleven questions regarding the use of VSD in abdominal surgeries were addressed: (1) which type of materials should be respectively chosen for the intraperitoneal cavity, retroperitoneal cavity and superficial incisions? (2) Can VSD be preventively used for a high-risk abdominal incision with primary suture? (3) Can VSD be used in severely contaminated/infected abdominal surgical sites? (4) Can VSD be used for temporary abdominal cavity closure under some special conditions such as severe abdominal trauma, infection, liver transplantation and intra-abdominal volume increment in abdominal compartment syndrome? (5) Can VSD be used in abdominal organ inflammation, injury, or postoperative drainage? (6) Can VSD be used in the treatment of intestinal fistula and pancreatic fistula? (7) Can VSD be used in the treatment of intra-abdominal and extra-peritoneal abscess? (8) Can VSD be used in the treatment of abdominal wall wounds, wound cavity, and defects? (9) Does VSD increase the risk of bleeding? (10) Does VSD increase the risk of intestinal wall injury? (11) Does VSD increase the risk of peritoneal adhesion? Focusing on these questions, evidence-based recommendations were given accordingly. VSD was strongly recommended regarding the questions 2-4. Weak recommendations were made regarding questions 1 and 5-11. Proper use of VSD in abdominal surgeries can lower the risk of infection in abdominal incisions with primary suture, treat severely contaminated/infected surgical sites and facilitate temporary abdominal cavity closure., (Copyright © 2019 Daping Hospital and the Research Institute of Surgery of the Third Military Medical University. Production and hosting by Elsevier B.V. All rights reserved.)

Necroptosis, a necrotic cell death pathway regulated by receptor interacting protein (RIP) 1 and 3, plays a key role in pathophysiological processes, including rheumatoid arthritis (RA). However, whether necroptosis is involved in RA articular cartilage damage processes remain unclear. The aim of present study was to investigate the dynamic changes in arthritic chondrocyte necroptosis and the effect of RIP1 inhibitor necrostatin-1 (Nec-1) and acid-sensing ion channels (ASICs) inhibitor amiloride on arthritic cartilage injury and acid-induced chondrocyte necroptosis. Our results demonstrated that the expression of RIP1, RIP3 and mixed lineage kinase domain-like protein phosphorylation (p-MLKL) were increased in adjuvant arthritis (AA) rat articular cartilage in vivo and acid-induced chondrocytes in vitro. High co-expression of ASIC1a and RIP1 showed in AA rat articular cartilage. Moreover, Nec-1 and amiloride could reduce articular cartilage damage and necroinflammation in AA rats. In addition, acid-induced increase in necroptosis markers RIP1/RIP3 were inhibited by Nec-1, ASIC1a-specific blocker psalmotoxin-1 (PcTx-1) or ASIC1a-short hairpin RNA respectively, which revealed that necroptosis is triggered in acid-induced chondrocytes and mediated by ASIC1a. These findings indicated that blocking ASIC1a-mediated chondrocyte necroptosis may provide potential therapeutic strategies for RA treatment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

4-Amino-2-Trifluoromethyl-Phenyl Retinate (ATPR), an all-trans retinoic acid (ATRA) derivative, possesses the ability to relief several carcinoma. Here, we explored the potential molecular mechanism of eukaryotic translation initiation factor 6 (eIF6) in ATPR-induced leukemia cell differentiation. Our research showed that ATPR could inhibit cell proliferation and promote cell differentiation in several leukemia cell lines. Besides, ATPR remarkably reduced the expression of eIF6 in vitro. Interestingly, the reduction of eIF6 contributed to restraining proliferation of K562 cells by inhibiting CyclinD1, C-myc and blocking cell cycle, as well as promoting differentiation of K562 cells by increasing the expression of C/EBPε, cell surface antigen CD11b and inducing renal-shrinkage of nuclear. Furthermore, the over-expression of eIF6 restrained the effects of ATPR on cell proliferation and maturation in K562 cells. In Addition, Notch1/CBF-1 signal activated by Chrysin could increase expression of eIF6 and restrain the differentiation in ATPR-induced K562 cells. Taken together, all above results indicated that ATPR induced differentiation of leukemia cells by decreasing eIF6 through Notch1/CBF-1 signal, which might exert an innovative treatment for leukemia., (Copyright © 2018. Published by Elsevier Inc.)

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the standard first-line treatment for EGFR-mutant nonsmall cell lung cancer (NSCLC) patients. However, studies have reported that not all NSCLC patients harboring kinase domain mutations in epidermal growth factor receptor (EGFR) show significant clinical benefits from EGFR-targeted tyrosine kinase inhibitors (TKIs). Therefore, it is necessary to establish feasible biomarkers to predict the prognosis of EGFR-mutant NSCLC patients treated with EGFR-TKIs. This study aimed to determine biomarkers using inflammatory parameters from complete blood counts to predict the prognosis of EGFR-mutant NSCLC patients treated with EGFR-TKIs.We retrospectively investigated 127 stage IIIB/IV NSCLC patients with activating EGFR mutations who were treated with EGFR-TKIs. We used receiver operating characteristic (ROC) curves to determine the optimal cut-off for the inflammatory markers as prognostic factors. Additionally, univariate and multivariate analyses were used to identify prognostic factors for progression-free survival (PFS) and overall survival (OS) of EGFR-mutant NSCLC patients treated with EGFR-TKIs.The receiver operating characteristic analysis indicated that the lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) cut-off values were 3.37 and 2.90, respectively. The univariate analysis showed that a high LMR (>3.37) and low NLR (≤2.90) were significantly correlated with long-term PFS and OS (LMR, P = .007; NLR, P < .001). The multivariate Cox regression analysis revealed that only low NLR was an independent prognostic factor for long-term PFS and OS (PFS, HR = 0.573, 95% CI: 0.340-0.964, P = .036; OS, HR = 0.491, 95% CI: 0.262-0.920, P = .026).The data show that a low NLR was a good prognostic factor in EGFR-mutant NSCLC patients receiving EGFR-TKIs treatment. Moreover, the NLR measurement has better prognostic value than LMR.

Competing Interests: None

Background: Serum level of Haptoglobin (Hp) maybe associated with Alzheimer's disease (AD) and mild cognitive impairment (MCI)., Objective: To investigate associations between serum Hp and AD, as well as between Hp and MCI., Methods: Serum levels of Hp were measured and analyzed for 51 patients with AD, 139 patients with MCI and their healthy controls matched with sex and age. All study subjects were from a survey among residents aged 60 years and over in a community located in the southwest suburb of Shanghai., Results: Serum levels of Hp were observed significantly higher in AD and MCI cases than controls (both p < 0.0001). A significant positive correlation was found between Hp and Activities of Daily Living (ADL) score (r s  = 0.430, p = 0.007), as well as between Hp and Clinical Dementia Rating (CDR) score (r s  = 0.359, p = 0.027) in all AD patients. According to the receiver operating characteristic (ROC) curve analysis, the optimal cut-off point for Hp was found to be 67.50 μg/ml (sensitivity, 0.902; specificity, 0.745) in AD patients, and 44.76 μg/ml (sensitivity, 0.986; specificity, 0.403) in MCI patients., Conclusion: Elevated serum levels of Hp were observed in AD and MCI patients than controls. In addition, Hp may correlate with the severity of AD., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Type 2 diabetes mellitus (T2DM) promotes a high oxidative stress and hypercoagulable state that drives microvascular injury and multiple-organ abnormality. Elevated thrombin activity underlies T2DM-linked endothelial dysfunction, but the mechanistic links between T2DM/oxidative stress axis and thrombin-associated endothelial pathologies are incompletely understood. In this work, immunohistochemical studies and quantitative analysis using isolated endothelial cells (ECs) identified accumulated Kru¨ppel-like family of transcription factor 14 (KLF14) deposits in ECs from multiple organs as distinct features of T2DM mice. KLF14 upregulation in ECs, which was stimulated by thrombin treatment, was dependent on multiple pathways including calcium mobilization, activation of PKC and AMPK pathways. Functionally, inhibition of endogenous KLF14 expression significantly attenuated thrombin-induced endotheliocyte proliferation, endothelial cell migration and oxidative stress. Molecularly, by directly binding the promoter, KLF14 functions as a transcriptional activator of PLK1, a polo-like kinase whose overexpression induced excessive reactive oxygen species (ROS) production. Transient knockdown of PLK1 was sufficient to suppress KLF14 overexpression-potentiated endothelial dysfunction. Collectively, these data provide proof of concept that deregulation of KLF14/PLK1 cascade plays a key role in thrombin-induced endothelial dysfunction and targeting KLF14 or PLK1 may limit thrombin-associated pathologies in T2DM patients., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Multidrug resistance (MDR) is the major impediment to cancer chemotherapy. The expression of lung resistance-related protein (LRP), a non-ATP-binding cassette (ABC) transporter, is high in tumor cells, resulting in their resistance to a variety of cytotoxic drugs. However, the function of LRP in tumor drug resistance is not yet explicit. Our previous studies had shown that Kinesin KIF4A was overexpressed in cisplatin (DDP)-resistant human lung adenocarcinoma cells (A549/DDP cells) compared with A549 cells. The expression of KIF4A in A549 or A549/DDP cells significantly affects cisplatin resistance but the detailed mechanisms remain unclear. Here, we performed co-immunoprecipitation experiments to show that the tail domain of KIF4A interacted with the N-terminal of LRP. Immunofluorescence images showed that both the ability of binding to LRP and the motility of KIF4A were essential for the dispersed cytoplasm distribution of LRP. Altogether, our results shed light on a potential mechanism in that motor protein KIF4A promotes drug resistance of lung adenocarcinoma cells through transporting LRP-based vaults along microtubules towards the cell membrane. Thus KIF4A might be a cisplatin resistance-associated protein and serves as a potential target for chemotherapeutic drug resistance in lung cancer.

The nonlinear magneto-optical rotation (NMOR) effect has prolific applications ranging from precision mapping of Earth's magnetic field to biomagnetic sensing. Studies on collisional spin relaxation effects have led to ultrahigh magnetic field sensitivities using a single-beam Λ scheme with state-of-the-art magnetic shielding/compensation techniques. However, the NMOR effect in this widely used single-beam Λ scheme is peculiarly small, requiring complex radio-frequency phase-locking protocols. We show the presence of a previously unknown energy symmetry-based nonlinear propagation blockade and demonstrate an optical inelastic wave-mixing NMOR technique that breaks this NMOR blockade, resulting in an NMOR optical signal-to-noise ratio (SNR) enhancement of more than two orders of magnitude never before seen with the single-beam Λ scheme. The large SNR enhancement was achieved simultaneously with a nearly two orders of magnitude reduction in laser power while preserving the magnetic resonance linewidth. This new method may open a myriad of applications ranging from biomagnetic imaging to precision measurement of the magnetic properties of subatomic particles.

Goethite-humic acid complex was prepared in a suspension containing goethite and humic acid. X-ray diffraction (XRD) results showed that the crystal structure of this complex had no obvious changes compared to pure goethite, but the peak intensity of the complex was slightly reduced. Transmission electron microscopy (TEM) images indicated that the surface of the goethite was coated by particles of humic acid. Compared to the infra-red (IR) spectra of goethite and humic acid, the anti-vibrational frequencies of COO - and the vibrational frequencies of ≡Fe-OH decreased by 20 cm -1 and 9 cm -1 , respectively, while the vibrational frequencies of the associated hydroxyls increased by 10 cm -1 and the absorption band of carboxylic C-O and free hydroxyls almost disappeared. This indicates that the interactional mechanisms between goethite and humic acid include the monodentate coordination of Fe(Ⅲ) -carboxylate and hydrogen-bonds. Thermogravimetry/differential thermogravimetry (TG/DTG) analysis showed that the temperature of the weight loss peak for ≡Fe-OH in goethite and the complex were 258℃ and 276℃, respectively. This indicates that the coating of humic acid enhances the heat stability of ≡Fe-OH in goethite. Compared with humic acid, the temperature of the weight loss peak for aliphatic organics and aromatic organics in complex decreased by 60℃ and 26℃, respectively and the ratio of weight loss from aliphatic organics to aromatic organics in complex increased. This indicates that organics with a lower heat stability may be more easily adsorbed onto goethite and the affinity to goethite was higher for the aliphatic organics than for aromatic organics. After ultrasonic dispersion, the content of large particles (≥ 2 μm) decreased significantly for both goethite and humic acid, but the content and the size of large particles in the complex changed only slightly.

Mechanistic insight into estrogen deficiency by polycystic ovary syndrome (PCOS) remains a longstanding challenge in reproductive medicine. Recent advance suggest that Wingless-type MMTV integration site family members (WNTs), in concert with its Frizzled (FZD) receptors, regulate normal folliculogenesis, luteogenesis and ovarian steroidogenesis. However, no studies have so far investigated any causality between WNT-FZDs interactions and disrupted estrogen synthesis under certain pathological conditions. Here, we show that (i) FZD3 expression was significantly up-regulated in the cumulus cells (CCs) from PCOS patients. This up-regulation, along with the activation of WNT2/β-Catenin pathway, was tightly associated with insulin resistance and estrogen deficiency, two hallmarks of PCOS. (ii) Overexpression of exogenous FZD3 in human granulosa cell COV434 impaired long-term FSH incubation-induced CYP19A1 transactivation and the recruitment of β-Catenin onto CYP19A1 promoter, and subsequently compromised FSH-stimulated estrogen production. (iii) Conversely, inhibition of FZD3 expression exhibited a therapeutic effect on estrogen synthesis in PCOS CCs. Thus, excessive FZD3 expression in CCs may act as a brake on steroidogenic activation that is normally overcome by FSH stimulation. Future endeavor in this field should help to elucidate the complicated crosstalk between energy metabolism and endocrine cells through WNT/FZD signaling molecules., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To investigate the epidemiology characteristics of crawfish related rhabdomyolysis (RM) in Nanjing, 2016., Methods: Outpatient and inpatient electronic medical system of 21 hospitals in Nanjing during 2016 were retrospectively searched, and all the patients diagnosed with RM were selected. The patients with none crayfish-related RM was excluded. The epidemiology characteristics were depicted. The geographic information system (GIS) was used to collect, manage and analyze the spatial data, to visualize it, to analyze the spatial distribution features of the disease, and to explore the cause of disease prediction. GeoDa 1.8 software was used to analyze the global and local spatial auto-correlation., Results: A total of 1 183 patients with crawfish related RM were initially screened, excluding 59 patients with RM caused by trauma, severe exercise, heat stroke, myositis, poisoning, drugs, and genetic diseases, and 1 124 patients were enrolled. The proportion of men was 36.48% (410/1 124) with an incidence of 12.54/100 thousands; while of women was 63.52% (714/1 124) with an incidence of 21.86/100 thousands. The median age at onset was 34 (28, 43) years. From July to August, the incidence of crawfish related RM was the highest, accounting for 96.53% of the total number of cases. The top four incidence areas were Pukou (41.54/100 thousands), Jianye (25.94/100 thousands), Qixia (25.73/100 thousands), Gulou (25.04/100 thousands), all of which were adjacent to the Yangtze River. Global spatial autocorrelation analysis showed: Moran I = 0.427, Z = 2.646, P = 0.003, suggesting that the crawfish related RM had positive spatial autocorrelation. The results showed that the spatial structure of crawfish related RM existed in Nanjing in 2016. Local spatial autocorrelation analysis showed that the "high-high" concentration areas were Pukou, Jianye and Liuhe. The incidences of above three areas which were the Nanjing section of the lower reaches of the Yangtze River flowed through the region and surrounding areas were higher than the overall incidence of Nanjing., Conclusions: The prevalence of crawfish related RM in Nanjing during 2016 had an obvious region-concentrated character and global spatial autocorrelation with the high prevalent regions mainly concentrated in the urban areas adjacent to the Yangtze River.

Predicting lymph node metastasis (LNM) accurately is of great importance to formulate optimal treatment strategies preoperatively for patients with early gastric cancer (EGC). This study aimed to explore risk factors that predict the presence of LNM in EGC. A total of 697 patients underwent gastrectomy enrolled in this study, were divided into training and validation set, and the relationship between LNM and other clinicopathologic features, preoperative serum combined tumor markers (CEA, CA19-9, CA125) were evaluated. Risk factors for LNM were identified using logistic regression analysis, and a nomogram was created by R program to predict the possibility of LNM in training set, while receiver operating characteristic (ROC) analysis was applied to assess the predictive value of the nomogram model in validation set. Consequently, LNM was significantly associated with tumor size, macroscopic type, differentiation type, ulcerative findings, lymphovascular invasion, depth of invasion and combined tumor marker. In multivariate logistic regression analysis, factors including of tumor size, differentiation type, ulcerative findings, lymphovascular invasion, depth of invasion and combined tumor marker were demonstrated to be independent risk factors for LNM. Moreover, a predictive nomogram with these independent factors for LNM in EGC patients was constructed, and ROC curve demonstrated a good discrimination ability with the AUC of 0.847 (95% CI: 0.789-0.923), which was significantly larger than those produced in previous studies. Therefore, including of these tumor markers which could be convenient and feasible to obtain from the serum preoperatively, the nomogram could effectively predict the incidence of LNM for EGC patients.

In the present study, we used Caenorhabditis elegans assay system to investigate in hormetic effects of imidazolium-based bromide Ionic Liquids (ILs) and explored the possible underlying mechanism. Firstly, C. elegans was treated with ILs with different alkyl chain lengths at different concentrations. We found that exposure to ILs at 0.01 mg/L extended the mean lifespan of C. elegans and the ILs with longer alkyl chain showed more obvious effects. To investigate the possible mechanism, the nematodes were exposed to the three ILs at 0.01 mg/L for 2, 5, 7, 9 and 11 days. The levels of reactive oxygen species (ROS) in C. elegans increased significantly when treated for 2 days and then declined gradually compared to those of respective controls as time went on. After exposure for 11 days, the ROS levels and liposuscin accumulation were significantly lower in the treated groups than those of control group. Meanwhile, the expression of aging-related genes sod-5 and daf-16 were both massively up-regulated for the three ILs examined. Our results show that low concentration of ILs exert hormetic effect on C. elegans. ROS generation and expression of aging-related genes may play important roles in the IL-induced hormetic effect on C. elegans., (Copyright © 2016 Elsevier Ltd. All rights reserved.)