Search

Qian Wu,1,* Qing-Qing Dong,1,* Si-Hui Wang,1 Yi Lu,1 Yi Shi,1 Xiao-Ling Xu,2 Wei Chen1 1ICU, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Shulan International Medical College, Zhejiang Shuren University, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Chen, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 725 South WanPing Road, Shanghai, 200032, People’s Republic of China, Tel +86-21-64385700-3522, Email cwdoctor@shutcm.edu.cn Xiao-Ling Xu, Shulan International Medical College, Zhejiang Shuren University, 8 Shuren Street, Hangzhou, 310015, People’s Republic of China, Email ziyao1988@zju.edu.cnBackground: Sepsis continues to exert a significant impact on morbidity and mortality in clinical settings, with immunosuppression, multi-organ failure, and disruptions in gut microbiota being key features. Although rheinic acid and tanshinone IIA show promise in mitigating macrophage apoptosis in sepsis treatment, their precise targeting of macrophages remains limited. Additionally, the evaluation of intestinal flora changes following treatment, which plays a significant role in subsequent cytokine storms, has been overlooked. Leveraging the innate inflammation chemotaxis of tumor cell-derived exosomes allows for their rapid recognition and uptake by activated macrophages, facilitating phenotypic changes and harnessing anti-inflammatory effects.Methods: We extracted exosomes from H1299 cells using a precipitation method. Then we developed a tumor cell-derived exosomal hybrid nanosystem loaded with rhubarbic acid and tanshinone IIA (R+T/Lipo/EXO) for sepsis treatment. In vitro studies, we verify the anti-inflammatory effect and the mechanism of inhibiting cell apoptosis of nano drug delivery system. The anti-inflammatory effects, safety, and modulation of intestinal microbiota by the nanoformulations were further validated in the in vivo study.Results: Nanoformulation demonstrated enhanced macrophage internalization, reduced TNF-α expression, inhibited apoptosis, modulated intestinal flora, and alleviated immunosuppression.Conclusion: R+T/Lipo/EXO presents a promising approach using exosomal hybrid nanosystems for treating sepsis. Keywords: sepsis, rheinic acid, tanshinone IIA, exosome, hybrid nanosystem

Yue Song,1,* Qing-Qing Dong,2,* Yi-Ke Ni,3 Xiao-Ling Xu,3 Chao-Xiang Chen,3 Wei Chen2 1Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310003, People’s Republic of China; 2ICU, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China; 3Shulan International Medical College, Zhejiang Shuren University, Hangzhou, Zhejiang Province, 310015, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao-Ling Xu; Chao-Xiang Chen, Shulan International Medical College, Zhejiang Shuren University, 8 Shuren Street, Hangzhou, 310015, People’s Republic of China, Email ziyao1988@zju.edu.cn; ccx@zjsru.edu.cnAbstract: Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules that have the capability to induce specific protein degradation. While playing a revolutionary role in effectively degrading the protein of interest (POI), PROTACs encounter certain limitations that impede their clinical translation. These limitations encompass off-target effects, inadequate cell membrane permeability, and the hook effect. The advent of nanotechnology presents a promising avenue to surmount the challenges associated with conventional PROTACs. The utilization of nano-proteolysis targeting chimeras (nano-PROTACs) holds the potential to enhance specific tissue accumulation, augment membrane permeability, and enable controlled release. Consequently, this approach has the capacity to significantly enhance the controllable degradation of target proteins. Additionally, they enable a synergistic effect by combining with other therapeutic strategies. This review comprehensively summarizes the structural basis, advantages, and limitations of PROTACs. Furthermore, it highlights the latest advancements in nanosystems engineered for delivering PROTACs, as well as the development of nano-sized PROTACs employing nanocarriers as linkers. Moreover, it delves into the underlying principles of nanotechnology tailored specifically for PROTACs, alongside the current prospects of clinical research. In conclusion, the integration of nanotechnology into PROTACs harbors vast potential in enhancing the anti-tumor treatment response and expediting clinical translation. Keywords: Proteolysis-targeting chimeras, nanotechnology, delivery, linker, designing principles

Wilson's disease is an autosomal recessive disorder of copper metabolism. Despite being treatable, there is no universally accepted treatment regimen. Currently, various Chinese herbal medicines (CHMs) are widely used in the treatment of Wilson's disease in China, but there is a lack of reliable scientific evidence for the effectiveness of such therapies. The objective of this systematic review is to assess the clinical efficacy and safety of CHM as an alternative or/and adjuvant therapy for Wilson's disease. A systematic literature search in different medical databases was performed to identify randomized controlled trials comparing CHM as monotherapy or CHM as adjuvant therapy with western conventional medical therapy in the treatment of Wilson's disease. A total of 687 participants were included in nine eligible studies. The main findings are that CHM as monotherapy or adjuvant therapy for Wilson's disease may be able to improve the clinical symptoms, to promote the urinary copper excretion, to ameliorate liver function and/or liver cirrhosis, and has fewer adverse effects in comparison with western conventional medication. Furthermore, CHM generally appeared to be safe and well tolerated in patients with Wilson's disease. However, the evidence presented in this review are insufficient to warrant a clinical recommendation due to the generally low methodological quality of the included studies. In conclusion, CHM seems to be beneficial and safe for Wilson's disease, but high-quality evidences are still needed to further evaluate this therapy. Therefore, additional well-designed, randomized, placebo-controlled clinical trials are needed.Copyright © 2012 by Elsevier Inc. [ABSTRACT FROM AUTHOR]

Liver fibrosis is a pathological process caused by a variety of chronic liver diseases. Currently, therapeutic options for liver fibrosis are very limited, highlighting the urgent need to explore new treatment approaches. Epigenetic modifications and epitranscriptomic modifications, as reversible regulatory mechanisms, are involved in the development of liver fibrosis. In recent years, researches in epitranscriptomics and epigenetics have opened new perspectives for understanding the pathogenesis of liver fibrosis. Exploring the epigenetic mechanisms of liver fibrosis may provide valuable insights into the development of new therapies for chronic liver diseases. This review primarily focus on the regulatory mechanisms of N6-methyladenosine (m6A) modification, non-coding RNA, and DNA methylation in organ fibrosis. It discusses the interactions between m6A modification and DNA methylation, as well as between m6A modification and non-coding RNA, providing a reference for understanding the interplay between epitranscriptomics and epigenetics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Dysregulated lipid oxidation occurs in several pathological processes characterized by cell proliferation and migration. Nonetheless, the molecular mechanism of lipid oxidation is not well appreciated in liver fibrosis, which is accompanied by enhanced fibroblast proliferation and migration., Methods: We investigated the causes and consequences of lipid oxidation in liver fibrosis using cultured cells, animal models, and clinical samples., Results: Increased ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP1) expression caused increased lipid oxidation, resulting in the proliferation and migration of hepatic stellate cells (HSCs) that lead to liver fibrosis, whereas fibroblast-specific ENPP1 knockout reversing these results. Elevated ENPP1 and N 6 -methyladenosine (m 6 A) levels were associated with high expression of Wilms tumor 1 associated protein (WTAP). Mechanistically, WTAP-mediated m 6 A methylation of the 3'UTR of ENPP1 mRNA and induces its translation dependent of YTH domain family proteins 1 (YTHDF1). Additionally, ENPP1 could interact with hypoxia inducible lipid droplet associated (HILPDA) directly; overexpression of ENPP1 further recruits HILPDA-mediated lipid oxidation, thereby promotes HSCs proliferation and migration, while inhibition of ENPP1 expression produced the opposite effect. Clinically, increased expression of WTAP, YTHDF1, ENPP1, and HILPDA, and increased m 6 A mRNA content, enhanced lipid oxidation, and increased collagen deposition in human liver fibrosis tissues., Conclusions: We describe a novel mechanism in which WTAP catalyzes m 6 A methylation of ENPP1 in a YTHDF1-dependent manner to enhance lipid oxidation, promoting HSCs proliferation and migration and liver fibrosis., (© 2024. The Author(s).)

Background: Dysregulated ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) family occurs in metabolic reprogramming pathological processes. Nonetheless, the epigenetic mechanisms by which ENPP family impacts NAFLD, also known as metabolic dysfunction-associated steatotic liver disease (MASLD), is poorly appreciated., Methods: We investigated the causes and consequences of ENPP1 promoter hypomethylation may boost NAFLD using NAFLD clinical samples, as well as revealed the underlying mechanisms using high-fat diet (HFD) + carbon tetrachloride (CCl 4 ) induced mouse model of NAFLD and FFA treatment of cultured hepatocyte., Results: Herein, we report that the expression level of ENPP1 are increased in patients with NAFLD liver tissue and in mouse model of NAFLD. Hypomethylation of ENPP1, is associated with the perpetuation of hepatocyte autophagy and liver fibrosis in the NAFLD. ENPP1 hypomethylation is mediated by the DNA demethylase TET3 in NAFLD liver fibrosis and hepatocyte autophagy. Additionally, knockdown of TET3 methylated ENPP1 promoter, reduced the ENPP1 expression, ameliorated the experimental NAFLD. Mechanistically, TET3 epigenetically promoted ENPP1 expression via hypomethylation of the promoter. Knocking down TET3 can inhibit the hepatocyte autophagy but an overexpression of ENPP1 showing rescue effect., Conclusions: We describe a novel epigenetic mechanism wherein TET3 promoted ENPP1 expression through promoter hypomethylation is a critical mediator of NAFLD. Our findings provide new insight into the development of preventative measures for NAFLD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Rationale: Vascular calcification (VC) is a life-threatening complication in patients with chronic kidney disease (CKD) caused mainly by hyperphosphatemia. However, the regulation of VC remains unclear despite extensive research. Although serum- and glucocorticoid-induced kinase 3 (SGK3) regulate the sodium-dependent phosphate cotransporters in the intestine and kidney, its effect on VC in CKD remains unknown. Additionally, type III sodium-dependent phosphate cotransporter-1 (Pit-1) plays a significant role in VC development induced by high phosphate in vascular smooth muscle cells (VSMCs). However, it remains unclear whether SGK3 regulates Pit-1 and how exactly SGK3 promotes VC in CKD via Pit-1 at the molecular level. Thus, we investigated the role of SGK3 in the certified outflow vein of arteriovenous fistulas (AVF) and aortas of uremic mice. Methods and Results: In our study, using uremic mice, we observed a significant upregulation of SGK3 and calcium deposition in certified outflow veins of the AVF and aortas, and the increase expression of SGK3 was positively correlated with calcium deposition in uremic aortas. In vitro , the downregulation of SGK3 reversed VSMCs calcification and phenotype switching induced by high phosphate. Mechanistically, SGK3 activation enhanced the mRNA transcription of Pit-1 through NF-κB, downregulated the ubiquitin-proteasome mediated degradation of Pit-1 via inhibiting the activity of neural precursor cells expressing developmentally downregulated protein 4 subtype 2 (Nedd4-2), an E3 ubiquitin ligase. Moreover, under high phosphate stimulation, the enhanced phosphate uptake induced by SGK3 activation was independent of the increased protein expression of Pit-1. Our co-immunoprecipitation and in vitro kinase assays confirmed that SGK3 interacts with Pit-1 through Thr468 in loop7, leading to enhanced phosphate uptake. Conclusion: Thus, it is justifiable to conclude that SGK3 promotes VC in CKD by enhancing the expression and activities of Pit-1, which indicate that SGK3 could be a therapeutic target for VC in CKD., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The critical role of oral colon-specific delivery systems (OCDDS) is important for delivering active agents to the colon and rectum specifically via the oral route. The use of micro/nanostructured OCDDS further improves drug stability, bioavailability, and retention time, leading to enhanced therapeutic effects. However, designing micro/nanoscale OCDDSs is challenging due to pH changes, enzymatic degradation, and systemic absorption and metabolism. Biodegradable natural polysaccharides are a promising solution to these problems, and β-glucan is one of the most promising natural polysaccharides due to its unique structural features, conformational flexibility, and specific processing properties. This review covers the diverse chemical structures of β-glucan, its benefits (biocompatibility, easy modification, and colon-specific degradation), and various β-glucan-based micro/nanosized OCDDSs, as well as their drawbacks. The potential of β-glucan offers exciting new opportunities for colon-specific drug delivery., Competing Interests: Declaration of competing interest The author declares no conflict of interest, financial or otherwise., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Focal segmental glomerulosclerosis (FSGS), a podocyte disease, is the leading cause of end-stage renal disease (ESRD). Nevertheless, the current effective treatment for FSGS is deficient. Curcumin (CUR) is a principal curcuminoid of turmeric, which is a member of the ginger family. Previous studies have shown that CUR has renoprotective effects. However, the mechanism of CUR in anti-FSGS is not clear. This study aimed to explore the mechanism of CUR against FSGS through a combination of network pharmacological methods and verification of experiments. The analysis identified 98 shared targets of CUR against FSGS, and these 98 targets formed a network of protein-protein interactions (PPI). Of these 98 targets, AKT1, TNF, IL-6, VEGFA, STAT3, MAPK3, HIF1A, CASP3, IL1B, and JUN were identified as the hub targets. Molecular docking suggested that the best binding to CUR is MAPK3 and AKT1. Apoptotic process and cell proliferation were identified as the main biological processes of CUR against FSGS by gene ontology (GO) analysis. The most enriched signaling pathway in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was the PI3K-AKT signaling pathway. Western blots and flow cytometry showed that CUR could inhibit adriamycin (ADR) induced apoptosis, oxidative stress damage, and attenuate podocyte epithelial-mesenchymal transition (EMT) by repressing the AKT signaling pathway. Collectively, our study demonstrates that CUR can attenuate apoptosis, oxidative stress damage, and EMT in FSGS in vitro. These results supply a compelling basis for future studies of CUR for the clinical treatment of FSGS., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Nav1.7, one of tetrodotoxin-sensitive voltage-gated sodium channels, mainly expressed in the small diameter dorsal root ganglion (DRG) neurons. The expression and accumulation on neuronal membrane of Nav1.7 increased following peripheral tissue inflammation or nerve injury. However, the mechanisms for membrane accumulation of Nav1.7 remained unclear. We report that KIF5b, a highly expressed member of the kinesin-1 family in DRGs, promoted the translocation of Nav1.7 to the plasma membrane in DRG neurons of the rat. Following nociceptive behaviors in rats induced by peripheral spared nerve injury (SNI), synchronously increased KIF5b and Nav1.7 expressions were observed in DRGs. Immunohistochemistry staining demonstrated the co-expressions of KIF5b and Nav1.7 in the same DRG neurons. Immunoprecipitation experiments further confirmed the interactions between KIF5b and Nav1.7. Moreover, intrathecal injections of KIF5b shRNA moderated the SNI-induced both mechanical and thermal hyperalgesia. The rescued analgesic effects also alleviated SNI-induced anxiety-like behaviors. In sum, KIF5b was required for the membrane localizations of Nav1.7, which suggests a novel mechanism for the trafficking of Nav1.7 involved in neuropathic pain., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Serum- and glucocorticoid-induced kinase 3 (SGK3), which is ubiquitously expressed in mammals, is regulated by estrogens and androgens. SGK3 is activated by insulin and growth factors through signaling pathways involving phosphatidylinositol-3-kinase (PI3K), 3-phosphoinositide-dependent kinase-1 (PDK-1), and mammalian target of rapamycin complex 2 (mTORC2). Activated SGK3 can activate ion channels (TRPV5/6, SOC, Kv1.3, Kv1.5, Kv7.1, BKCa, Kir2.1, Kir2.2, ENaC, Nav1.5, ClC-2, and ClC Ka), carriers and receptors (Npt2a, Npt2b, NHE3, GluR1, GluR6, SN1, EAAT1, EAAT2, EAAT4, EAAT5, SGLT1, SLC1A5, SLC6A19, SLC6A8, and NaDC1), and Na + /K + -ATPase, promoting the transportation of calcium, phosphorus, sodium, glucose, and neutral amino acids in the kidney and intestine, the absorption of potassium and neutral amino acids in the renal tubules, the transportation of glutamate and glutamine in the nervous system, and the transportation of creatine. SGK3-sensitive transporters contribute to a variety of physiological and pathophysiological processes, such as maintaining calcium and phosphorus homeostasis, hydro-salinity balance and acid-base balance, cell proliferation, muscle action potential, cardiac and neural electrophysiological disturbances, bone density, intestinal nutrition absorption, immune function, and multiple substance metabolism. These processes are related to kidney stones, hypophosphorous rickets, multiple syndromes, arrhythmia, hypertension, heart failure, epilepsy, Alzheimer's disease, amyotrophic lateral sclerosis, glaucoma, ataxia idiopathic deafness, and other diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liao, Dong, Zhang, Shu, Tu and Yao.)

The acute lung injury (ALI) causes severe pulmonary diseases, leading to a high mortality rate. The Renshen and Chishao have protective and anti-inflammatory effects against the ALI. To explore the protective effects of the Renshen Chishao (RC) decoction against the ALI, we established the lipopolysaccharide-indued ALI model and randomly divided the mice into seven groups: control group, ALI group, high-dose RC group, middle-dose RC group, low-dose RC group, middle-dose RC group + CXCR2 antagonist group, and ALI + CXCR2 antagonist group. We estimated the lung injury by the hematoxylin and eosin staining, the neutrophil extracellular traps (NETs) formations by the immunofluorescence colocalization and enzyme-linked immunosorbent assay (ELISA), and the CXCR2/CXCL2 pathway by the flow cytometry, ELISA, and real-time polymerase chain reaction. We conducted the high-throughput sequencing and enrichment analyses to explore the potential mechanisms. The results showed that the RC decoction pathologically ameliorated the lipopolysaccharide-induced lung injury and inflammatory response but failed to reduce the circulating and lung tissue NETs formation and the blood neutrophil percent. The high-dose RC decoction increased the plasma CXCL2 level, but the RC decoction had no effects on the neutrophilic CXCR2 levels. Under the inhibition of the CXCR2, the middle-dose RC decoction still decreased the lung injury score but as yet had unobvious influence on the NETs formation. Other potential mechanisms of the RC decoction against the ALI involved the pathways of ribosome and coronavirus disease 2019 (COVID-19); the target genes of inflammatory factors, such as Ccl17, Cxcl17, Cd163, Cxcr5, and Il31ra , and lncRNAs; and the regulations of the respiratory cilia. In conclusion, the RC decoction pathologically ameliorated the lipopolysaccharide-induced lung inflammatory injury via upregulating the CXCL2/CXCR2 pathway but could not reduce the circulating or lung tissue NETs formation., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2022 Miao-En Yao et al.)

Objective: T-LAK-cell-originated protein kinase (TOPK), a PSD95-Disc large-ZO1 (PDZ) binding kinase (PBK), is a novel member of the mitogen-activated protein kinase (MAPK) family. Studies have shown that TOPK plays a critical role in the function of tumor cells, including apoptosis and mitosis. However, little is known on the effect of TOPK in cisplatin-induced acute kidney injury (CP-AKI). This study aimed to investigate the role and mechanism of TOPK in CP-AKI., Methods: Cisplatin was administered to C57BL/6 mice and cultured kidney tubular epithelial cells (TECs) to establish the CP-AKI murine or cellular models. TECs were then stimulated with the specific inhibitor of TOPK OTS514 or transfected with the recombinant-activated plasmid TOPK-T9E to inhibit or activate TOPK. The TECs were treated with AKT inhibitor VIII following stimulation with OTS514 or cisplatin. Western blotting and flow cytometry were used to evaluate the cell cycle and apoptosis of TECs., Results: The analysis revealed that the TOPK activity was significantly suppressed by cisplatin, both in vivo and in vitro. Furthermore, the pharmacological inhibition of TOPK by OTS514, a specific inhibitor of TOPK, exacerbated the cisplatin-induced cell cycle arrest in the G2/M phase and apoptosis of cultured TECs. Moreover, the TOPK activation via the TOPK-T9E plasmid transfection could partially reverse the cell cycle arrest at the G2/M phase and apoptosis of cisplatin-treated TECs. In addition, AKT/protein kinase B (PKB), as a TOPK target protein, was inhibited by cisplatin in cultured TECs. The pharmaceutical inhibition of AKT further aggravated the apoptosis of TECs induced by cisplatin or TOPK inhibition. TOPK systematically mediated the apoptosis via the AKT pathway in the CP-AKI cell model., Conclusion: These results indicate that TOPK activation protects against CP-AKI by ameliorating the G2/M cell cycle arrest and cell apoptosis., (© 2022. The Author(s).)

Previous studies on the global burden of caries primarily focused on simple descriptive statistics. We aimed to characterize the burden, trends, and inequalities of untreated caries of permanent and deciduous teeth from 1990 to 2019 at the global, regional, and national levels through an array of analytic approaches. Estimates of caries burden were extracted from the Global Burden of Disease Study 2019. Decomposition analysis was performed to examine the contribution of demographic and epidemiologic factors to the evolving number of prevalent caries cases. In portfolio analysis, the caries epidemiologic profile of each country was categorized by terciles of age-standardized prevalence in 2019 and average annual percentage change from 1990 to 2019. Sociodemographic attribution analysis was performed to reveal the scale of inequality in burden of caries. Age-standardized prevalence of caries in permanent and deciduous teeth decreased 3.6% (95% uncertainty interval, 2.6% to 4.5%) and 3.0% (1.3% to 4.9%), respectively. Population growth was the key driver of the changes in the number of caries cases, especially in sub-Saharan Africa (percentage contribution: 126.6%, permanent teeth; 103.0%, deciduous teeth). Caries prevalence in the permanent dentition was lower in more developed countries, whereas a reverse trend was noted in the deciduous dentition, except for the highest sociodemographic quintile where caries prevalence was the lowest. Globally, 64.6 million (95% CI, 64.4 to 64.9 million) and 62.9 million (62.8 to 63.1 million) prevalent cases of caries in permanent and deciduous teeth were attributable to sociodemographic inequality in 2019. This amounted to 3.2% (3.2% to 3.2%) and 12.1% (12.1% to 12.1%) of the global number of prevalent cases of caries in permanent and deciduous teeth. Burden of dental caries remains a global public health challenge. A systemwide reform of the global oral health care system is needed to tackle the causes of the burden and inequality of dental caries.

Serum and glucocorticoid-inducible kinase 3 (SGK3) is involved in maintaining podocyte function by regulating the protein levels of podocin and CD2-associated protein. Nephrin is also one of the slit diaphragm proteins of podocytes, but whether SGK3 participates in podocyte injury by regulating the levels of nephrin remains unclear. In this study, we focused on whether SGK3 affects nephrin levels and the mechanisms involved in the same. In the kidneys of adriamycin (ADR)-induced podocyte injury mouse model, the protein levels of SGK3 and nephrin were significantly decreased. Furthermore, the expression of SGK3 was negatively correlated with the output of proteinuria, and positively correlated with the levels of nephrin. In ADR-treated conditionally immortalized mouse podocyte cells (MPCs), the protein levels of nephrin and SGK3 were inhibited, while the constitutive expression of SGK3 reversed the ADR-induced decline in nephrin protein levels. Furthermore, ADR treatment or SGK3 inactivation enhanced the ubiquitin-proteasome degradation of nephrin in MPCs, and dramatically activated downstream effector proteins of SGK3, neural precursor cells expressing developmentally downregulated protein 4 subtype 2 (Nedd4-2) and glycogen synthase kinase-3 β (GSK3β). Similarly, Nedd4-2 or GSK3β overexpression resulted in increased activity of Nedd4-2 or GSK3β, and significantly downregulated nephrin levels. Interestingly, ubiquitin-mediated protein degradation of nephrin was regulated by Nedd4-2, rather than by GSK3β. In summary, SGK3 inactivation downregulated the levels of nephrin by increasing Nedd4-2 and GSK3β activity in ADR-induced podocyte injury model; in particular, the SGK3/Nedd4-2 signaling pathway was found to be involved in ubiquitin-mediated proteasome degradation of nephrin., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dong, Li, Zhang, Shu, Tu, Liao and Yao.)

Cisplatin-induced acute kidney injury (CP-AKI) is a severe complication in patients receiving CP chemotherapy. However, effective therapies for CP-AKI are currently lacking. Curcumin (CUR), a natural polyphenol, is extracted from the rhizome of turmeric and has been reported to have nephroprotective activity. However, the role of CUR in CP-AKI remains unclear. This study aimed to explore the mechanism of CUR in CP-AKI by combining a network pharmacology approach with experimental validations. The analysis revealed 176 potential targets of CUR based on the HERB database and 1,286 related targets of CP-AKI from the GeneCards, DrugBank, and OMIM databases. Further, 106 common targets of CUR against CP-AKI were obtained, and these common targets constructed a protein-protein interaction (PPI) network. In addition, the core targets were screened from the PPI network using Cytoscape. Molecular docking revealed that CUR displayed the best binding to AKT1. Gene Ontology (GO) analysis indicated that the primary biological processes of CUR against CP-AKI included cellular response to chemical stress and apoptotic regulation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis suggested that the PI3K-Akt signaling pathway was most significantly enriched in CUR against CP-AKI. Western blotting and flow cytometry showed that CUR inhibited apoptosis induced by CP by activating the Akt signaling pathway in human kidney tubular epithelial cells (HK-2). Altogether, our findings demonstrated that CUR alleviated apoptosis by activating the Akt signaling pathway in CP-AKI in vitro . These data provide a scientific basis for future investigations into the clinical application of CUR against CP-AKI.

Vertical expansion makes the structure and pattern of the city more complicated. Traditional two-dimensional landscape pattern cannot completely reflect the ecological structure and functional characteristics of urban landscape. In this study, we used the three-dimensional landscape pattern metrics to quantify the regional three-dimensional landscape pattern, and used boosted regression tree (BRT) machine learning algorithms to comprehensively analyze the interaction between social-environmental factors and urban landscape patterns in the central part of Shanghai. Results showed that high building ratio, mean architecture height, and architecture height standard deviation had higher values in the surrounding area of the inner ring. The number of buildings and landscape shape index were higher in the outer ring than those in other area. Building coverage ratio, floor area ratio and Shannon's diversity index had higher values in the central part, with the metrics of Puxi being generally higher than those of Pudong. Population density and normalized vegetation index (NDVI) interacted most significantly with the three-dimensional landscape pattern, with GDP as the least influential factor. Within a certain range, the three-dimensional landscape pattern metrics increased with larger population density in the social factors, and decreased with lower rate of NDVI and water surface ratio in the environmental factors. Our results demonstrated that the BRT method was effective in quantifying the interaction between landscape pattern and social-environmental factors. Our results help improve the understanding of the relationship between ecological environment and human well-being in the central part of Shanghai and provide a scientific basis for the urban three-dimensional expansion planning.

Aim: Up-to-date epidemiological studies on the global burden of severe periodontitis is scarce. This study aimed to present the latest estimates for prevalence of severe periodontitis from 1990 to 2019, by region, age, and level of socio-demographic development., Materials and Methods: Estimates from the Global Burden of Disease study 2019 were used to investigate burden and trends of prevalence of severe periodontitis and its association with socio-demographic development at global, regional, and national level. Decomposition analysis was performed to explore the contribution of demographic and epidemiological factors to the evolving burden of severe periodontitis., Results: In 2019, there were 1.1 billion (95% uncertainty interval: 0.8-1.4 billion) prevalent cases of severe periodontitis globally. From 1990 to 2019, age-standardized prevalence rate of severe periodontitis increased by 8.44% (6.62%-10.59%) worldwide. Prevalence of severe periodontitis is higher among less developed countries/regions. Global population growth accounted for 67.9% of the increase in the number of prevalent cases of severe periodontitis from 1990 to 2019., Conclusions: The global burden of severe periodontitis has been substantial and increasing over the past three decades. Upstream policy changes are urgently needed to address the global public health challenge of severe periodontitis., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Accurate appraisal of burden of adolescents and young adults (AYAs) cancers is crucial to informing resource allocation and policy making. We report on the latest estimates of burden of AYA cancers in 204 countries and territories between 1990 and 2019 in association with socio-demographic index (SDI)., Patients and Methods: Estimates from the Global Burden of Disease study 2019 were used to analyse incidence, mortality, and disability-adjusted life years (DALYs) due to AYA cancers at global, regional, and national levels by sex. Association between AYA cancer burden and SDI were investigated. Burdens of AYA cancers were contextualized in comparison with childhood and older adult cancers. All estimates are reported as counts and age-standardized rates per 100,000 person-years., Results: In 2019, there were 1.2 million incident cases, 0.4 million deaths, and 23.5 million DALYs due to AYA cancers globally. The highest age-standardized incidence rate occurred in Western Europe (75.3 [Females] and 67.4 [Males] per 100,000 person-years). Age-standardized death (23.2 [Females] and 13.9 [Males] per 100,000 person-years) and DALY (1328.3 [Females] and 1059.2 [Males] per 100,000 person-years) rates were highest in Oceania. Increasing SDI was associated with a higher age-standardized incidence rate. An inverted U-shaped association was identified between SDI and death and DALY rates. AYA cancers collectively is the second leading cause of non-communicable diseases-related deaths globally in 2019. DALYs of AYA cancers ranked the second globally and the first in low and low-middle SDI locations when compared with that of childhood and older adult cancers., Conclusion: The global burden of AYA cancers is substantial and disproportionally affect populations in limited-resource settings. Capacity building for AYA cancers is essential in promoting equity and population health worldwide.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 is challenging the dental community to an unprecedented degree. Knowledge of the increased risk of infection in dental settings has been disseminated to the public and guidelines have been formulated to assist dental attendance decision-making. However, dental attendance behaviors incompatible with treatment need is not uncommon in clinical settings. Important gaps remain in the knowledge about how psychological factors are affecting dental attendance behaviors during the COVID-19 epidemic. In this cross-sectional study, a questionnaire survey was performed during February and March 2020. A total of 342 and 294 dental patients who attended and avoided dental visits, respectively, were included. The participants were classified into four groups based on dental attendance behavior and emergent/urgent dental treatment need. Bivariate analysis was performed to investigate factors associated with dental attendance. Multivariable logistic regression based on principal component scores was performed to identify major psychological constructs associated with unnecessary dental avoidance and attendance. Among all the factors explored, inability to wear masks during dental treatment ( P < 0.001; effect size: 0.32) was most closely associated with the overall pattern of dental attendance among participants. Multivariable regression suggested that unnecessary dental avoidance was associated with perceived risk of infection in general and in dental settings (odds ratio [95% CI]: 0.62 [0.53, 0.72]; p < 0.001), perceived impact of COVID-19 and dental problems on general health (0.79 [0.65, 0.97]; 0.021), and personal traits such as trust and anxiety (0.77 [0.61, 0.98]; 0.038). Unnecessary dental attendance was associated with optimism toward the epidemic (1.68 [1.42, 2.01]; <0.001) and trust (1.39 [1.13, 1.74]; 0.002). Multidisciplinary efforts involving dental and medical professionals as well as psychologists are warranted to promote more widespread adoption, among the general public, of dental attendance behaviors compatible with dental treatment need during the COVID-19 epidemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer MZ declared a shared affiliation with several of the authors, PF, SW, and XL, to the handling editor at time of review., (Copyright © 2021 Wen, Fang, Peng, Wu, Liu and Dong.)

Liraglutide is an analog of human glucagon-like peptide-1 which play essential roles in regulation of glycolipid metabolism. To investigate role of lactic acid bacteria (LAB) in lipid-lowering effect of liraglutide, 40 mice were divided into normal food diet (NFD), high-fat food (HFD), 10.0 mg/kg/d simvastatin-treated HFD (SIM + HFD), 200 and 400 µg/kg/d liraglutide-treated HFD (LL + HFD and HL + HFD) groups for 5 weeks. We found that liraglutide could upregulate cholesterol 7α-hydroxylase (CYP7A1) and LDL-receptor (LDLR), whereas downregulate 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Besides, liraglutide enhance abundance of lactobacillaceae in gut of hyperlipidemic mice and increase bile tolerance ability of LAB by upregulating bile salt hydrolases, and the lysate of liraglutide-sensitive LAB could also directly downregulate HMGCR, the key enzyme in cholesterol synthesis, and inhibit hepatocyte steatosis. These findings might provide new theoretical guidance for clinical application of liraglutide and research and development of antiobesity, hypolipidemic, and cholesterol-lowering drugs or functional foods., (© The Author(s) 2021. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Background: Vacuum sealing drainage (VSD) and epidermal growth factor (EGF) both play an important role in the treatment of wounds. This study aims to explore the effects of the combination of VSD and EGF on wound healing and the optimal concentration and time of EGF., Methods: We tested the proliferation and migration capacity of HaCaT and L929 cells at different EGF concentrations (0, 1, 5, 10, and 100 ng/ml) and different EGF action times (2, 10, and 30 min). A full-thickness skin defect model was established using male, 30-week-old Bama pigs. The experiment included groups as follows: routine dressing change after covering with sterile auxiliary material (Control), continuous negative pressure drainage of the wound (VSD), continuous negative pressure drainage of the wound and injection of EGF 10 min followed by removal by continuous lavage (V + E 10 min), and continuous negative pressure drainage of the wound and injection of EGF 30 min followed by removal by continuous lavage (V + E 30 min). The wound healing rate, histological repair effect and collagen deposition were compared among the four groups., Results: An EGF concentration of 10 ng/ml and an action time of 10 min had optimal effects on the proliferation and migration capacities of HaCaT and L929 cells. The drug dispersion effect was better than drug infusion after bolus injection effect, and the contact surface was wider. Compared with other groups, the V + E 10 min group promoted wound healing to the greatest extent and obtained the best histological score., Conclusions: A recombinant human epidermal growth factor (rhEGF) concentration of 10 ng/ml can promote the proliferation and migration of epithelial cells and fibroblasts to the greatest extent in vitro. VSD combined with rhEGF kept in place for 10 min and then washed, can promote wound healing better than the other treatments in vivo.

Objective: Maternal vitamin D deficiency is associated with glucose and lipid metabolism in the mother and offspring. Meanwhile, it can also lead to adverse pregnancy outcomes. The aim of this case-control study was to document maternal, umbilical arterial glucose and lipid metabolic levels and correlations in pregnancies with or without vitamin D deficiency, while also investigating adverse pregnancy outcomes., Design/participants/measurements: A total of 425 pregnant women who received antenatal care and delivered at Wenzhou People's Hospital were enrolled. According to their serum 25-hydroxyvitamin D [25(OH)D] level, the pregnant women were divided into the vitamin D deficiency group [25(OH)D < 20 ng/mL, 185 participants] and the control group [25(OH)D ≥ 20 ng/mL, 240 participants]. Maternal blood samples were collected at 24-28 weeks of gestation and delivery for 75-g oral glucose tolerance test (OGTT), and measurements of glucose and lipid metabolite levels and 25(OH)D levels. Umbilical arterial samples were collected during delivery (33.57-41.43 gestational weeks)., Results: Compared with control participants, vitamin D deficiency women had significantly higher concentrations of fasting blood-glucose (P < .01), 1-h OGTT plasma glucose (P < .01), 2-h OGTT plasma glucose (P < .01), insulin (P < .01), HOMA-IR (P < .01), LDL (P < .01) and triglycerides (P = .02) and lower concentrations of HOMA-S (P < .01). Compared with the control group, vitamin D deficiency women had higher concentrations of triglycerides (P < .01) and lower concentrations of HDL-C (P < .01) and HOMA-β (P = .01) in infant umbilical arterial blood. Pearson's correlation analysis demonstrated that the maternal 25(OH)D level was negatively correlated with maternal plasma glucose, insulin, LDL-C, cholesterol, triglyceride and HOMA-IR (r = -.38, -.27, -.2, -.11, -.11, -.33 and .11; P < .01, <.01, <.01, <.05, <.05 and <.01, respectively), while there was a positive correlation between maternal serum 25(OH)D and HOMA-S (r = .11, P < .05). The triglyceride level in the umbilical artery was negatively correlated with maternal serum 25(OH)D concentration (r = -.286, P < .01), while the HDL-C and HOMA-β in umbilical artery were positively related (r = .154, .103, P < .01). Compared with the control group, the incidences of pre-eclampsia [4.8% (9/185) vs 1.25% (3/240), P = .03], gestational diabetes mellitus [19.45% (36/185) vs 12.08% (29/240), P = .04] and premature rupture of membranes [15.68% (29/185) vs 5.42% (13/240), P < .01] were higher in the vitamin D deficiency group., Conclusion: Vitamin D deficiency during pregnancy is associated with maternal glucose and lipid metabolism and pregnancy outcomes. Therefore, it is worth recommending to maintain vitamin D status at an optimal level in pregnant women to prevent metabolic disorders and pregnancy complications., (© 2020 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

In the period of regular epidemic prevention and control of Coronavirus disease 2019 (COVID-19) in our country, work resumption has been fully advanced. But there are still new sporadic local cases and imported cases across the country. In this situation, whether kindergartens reopening will increase the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread still remains uncertain. We reviewed two pediatric patients with moderate COVID-19, collected the epidemiologic information and monitored the cycle threshold value of rectal specimen and the viral loads, and discussed the transmission of SARS-CoV-2 in pediatric patients and the virulence of feces in children with moderate COVID-19, in order to analyze the risk of kindergartens reopening.

Cisplatin resistance has been a major factor limiting its clinical use as a chemotherapy drug. The present study aimed to investigate whether SET and MYND domain-containing protein 3 (SMYD3), a histone methyltransferase closely associated with tumors can affect the sensitivity of tumors to cisplatin chemotherapy. Real time-qPCR, western blotting, the luciferase reporter, MTT and clonogenic assays were performed to detect the effects of SMYD3 on the chemotherapy capacity of cisplatin. In the present study, SMYD3 exhibited different expression patterns in MCF-7 and T47D breast cancer cells. In addition, this differential expression was associated with tumor cell resistance to cisplatin. Furthermore, SMYD3 knockdown following small interfering RNA transfection increased cisplatin sensitivity, whereas SMYD3 overexpression decreased cisplatin sensitivity. In addition, SMYD3 knockdown synergistically enhanced cisplatin-induced cell apoptosis. SMYD3 expression was downregulated during cisplatin treatment. In addition, transcriptional regulatory activities of SMYD3 3'-untranslated region were also downregulated. These results suggested that SMYD3 may affect cell sensitivity to cisplatin and participate in the development of cisplatin resistance, which is a process that may involve microRNA-124-mediated regulation., (Copyright: © Wang et al.)

Background: Conventional treatment has limited efficacy in relapsed/refractory B-cell lymphoma. Since chimeric antigen receptor T-cell (CAR-T) technology has shown high safety and results in high remission rates, we investigated its efficacy and safety in B-cell lymphoma treatment and analyzed potential affecting factors to provide evidence for therapeutic strategies and applications., Methods: We searched databases including PubMed, Embase, and Cochrane up to July 2019. Meta-analysis 1 was conducted to study the efficacy of CAR-T cell for treating B-cell lymphoma, measuring the response rate and complete remission rate as outcomes. Sub-group analysis was performed for age, pathological type, target antigen, co-stimulatory molecule, and conditioning chemotherapy. Meta-analysis 2 was undertaken on the safety of the treatment with the incidence rate of toxicity (cytokine-releasing syndrome [CRS], neurotoxicity) as an outcome., Results: Seventeen studies were included in the systematic review and meta-analysis. It was found that CAR-T cells had good therapeutic effects in the following cases: B-cell lymphoma (patients ≥65 years old); diffuse large B-cell lymphoma pathological type; patients with treatment target antigen other than CD19; patients treated with co-stimulatory molecules other than CD28, including 4-1BB+CD28 or 4-1BB; and patients treated with cyclophosphamide/fludarabine pre-treatment protocol conditioning chemotherapy. Although the CRS and neurotoxicity incidences were high, most were reversible with minimal risk of death., Conclusion: CAR-T cell treatment is safe for clinical application; however, toxicity effects should be monitored.

Background: Transesophageal echocardiography may be used to assess pulmonary veins for atrial fibrillation ablation. No study focused on the role of transthoracic echocardiography (TTE) in evaluating the diameter and anatomy of pulmonary veins., Methods: Among 142 atrial fibrillation patients (57.7% men; mean age, 60.5) hospitalised for catheter ablation, we assessed pulmonary veins and compared the measurements by TTE with cardiac computed tomography (CT) before ablation. Among 17 patients who had follow-up examinations, the second measurements were also studied., Results: TTE identified and determined the diameters of 140 (98.6%) right and 140 (98.6%) left superior PVs, and 136 (95.7%) right and 135 (95.1%) left inferior PVs. A separate middle PV ostia was identified in 14 out of the 22 patients (63.6%) for the right side and in 2 out of 4 (50.0%) for the left side. The PV diameters before ablation assessed by CT vs. TTE were 17.96 vs. 18.07 mm for right superior, 15.92 vs. 15.51 mm for right inferior, 18.54 vs. 18.42 mm for left superior, and 15.56 vs. 15.45 mm for left inferior vein. The paired differences between the assessments of CT and TTE were not significant (P ≥ 0.31) except for the right inferior vein with a CT-minus-TTE difference of 0.41 mm (P = 0.018). The follow-up PV diameters by both CT (P ≥ 0.069) and TTE (P ≥ 0.093) were not different from baseline measurements in the 17 patients who had follow-up measurements., Conclusions: With a better understanding of PV anatomy in TTE imaging, assessing PV diameters by non-invasive TTE is feasible. However, the clear identification of anatomic variation might still be challenging.

Indoleamine 2,3-dioxygenase 1 (IDO1), an important immunoregulatory enzyme ubiquitously expressed in various tissues and cells, plays a key role in tryptophan metabolism via the kynurenine pathway and has emerged as an attractive therapeutic target for the treatment of cancer and other diseases, such as Alzheimer's disease and arthritis. IDO1 has diverse biological roles in immune suppression and tumor progression by tryptophan catabolism. In addition, IDO1-mediated immune tolerance assists tumor cells in escaping the immune surveillance. Recently, extensive and enormous investigations have been made in the discovery of IDO1 inhibitors in both academia and pharmaceutical companies. In this review, IDO1 inhibitors are grouped as tryptophan derivatives, inhibitors with an imidazole, 1,2,3-triazole or tetrazole scaffold, inhibitors with quinone or iminoquinone, N -hydroxyamidines and other derivatives, and their enzymatic inhibitory activity, selectivity and other biological activities are also introduced and summarized., (This journal is © The Royal Society of Chemistry 2019.)

Trehalose is used as an additive in thousands of foods, cosmetics, and pharmaceutical products, and it is being investigated as a therapeutic for multiple human diseases. However, its ability to be used as a carbon source by microbes is a concern, as highlighted by the recent finding that trehalose can be metabolized by and potentially enhance the virulence of epidemic Clostridioides difficile. Here, we show that trehalose analogues designed to resist enzymatic degradation are incapable of being used as carbon sources by C. difficile. Furthermore, we demonstrate that trehalose analogues, but not the known trehalase inhibitor validamycin A, inhibit native trehalose utilization by hypervirulent C. difficile. Thus, degradation-resistant trehalose analogues are valuable as trehalase inhibitors and as surrogates for or co-additives with trehalose in applications where enzymatic breakdown is a concern.

Sulforaphane (SFN), a natural compound derived from cruciferous vegetables, has been proved to possess potent anti-cancer activity. SMYD3 is a histone methyltransferase which is closely related to the proliferation and migration of cancer cells. This study showed that SFN could dose-dependently induce cell cycle arrest, stimulate apoptosis, and inhibit proliferation and migration of gastric carcinoma cells. Accompanied with these anti-cancer effects, SMYD3 and its downstream genes, myosin regulatory light chain 9, and cysteine-rich angiogenic inducer 61, was downregulated by SFN. Furthermore, overexpression of SMYD3 via transfection could abolish the effects of SFN, suggesting that SMYD3 might be an important mediator of SFN. To the best of our knowledge, this is the first report describing the role of SMYD3 in the anti-cancer of SFN. These findings might throw light on the development of novel anti-cancer drugs and functional food using SFN-rich cruciferous vegetables., Competing Interests: Compliance with ethical standardsThe authors declare no conflict of interest.

Purpose: We previously found that the histone methyltransferase suppressor of variegation, enhancer of zeste, trithorax and myeloid-nervy-deformed epidermal autoregulatory factor-1 domain-containing protein 3 (SMYD3) is a potential independent predictive factor or prognostic factor for overall survival in gastric cancer patients, but its roles seem to differ from those in other cancers. Therefore, in this study, the detailed functions of SMYD3 in cell proliferation and migration in gastric cancer were examined., Materials and Methods: SMYD3 was overexpressed or suppressed by transfection with an expression plasmid or siRNA, and a wound healing migration assay and Transwell assay were performed to detect the migration and invasion ability of gastric cancer cells. Additionally, an MTT assay and clonogenic assay were performed to evaluate cell proliferation, and a cell cycle analysis was performed by propidium iodide staining. Furthermore, the expression of genes implicated in the ataxia telangiectasia mutated (ATM) pathway and proteins involved in cell cycle regulation were detected by polymerase chain reaction and western blot analyses., Results: Compared with control cells, gastric cancer cells transfected with si-SMYD3 showed lower migration and invasion abilities (P < 0.05), and the absence of SMYD3 halted cells in G2/M phase and activated the ATM pathway. Furthermore, the opposite patterns were observed when SMYD3 was elevated in normal gastric cells., Conclusions: To the best of our knowledge, this study provides the first evidence that the absence of SMYD3 could inhibit the migration, invasion, and proliferation of gastric cancer cells and halt cells in G2/M phase via the ATM-CHK2/p53-Cdc25C pathway. These findings indicated that SMYD3 plays crucial roles in the proliferation, migration, and invasion of gastric cancer cells and may be a useful therapeutic target in human gastric carcinomas., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported.

Background: This study was aimed to evaluate the feasibility and accuracy of real-time three-dimensional echocardiography (RT-3DE) measurement of left atrial (LA) volume and function in comparison with two-dimensional echocardiography (2DE) measurements in atrial fibrillation (AF) patients., Methods: A total of 50 pairs of AF patients and healthy controls were enrolled in this study. Indexed LA end-diastole volume (ILAEDV) and indexed LA end-systolic volume (ILAESV), as well as LA function indices such as segmental LA ejection fraction (LAEF), were assessed using 2DE Simpson's method and the RT-3DE method., Results: The images showed that regional LA volume-time curves and LAEF were disordered in AF patients. ILAEDV and ILAESV were markedly increased and global LAEF was significantly decreased in AF patients compared with those in healthy controls (P < 0.01). No significant differences were found in ILAEDV, ILAESV, and LAEF levels as determined by the RT-3DE method or 2DE Simpson's method. Bland-Altman analysis showed that the two methods agreed well for measuring ILAEDV, ILAESV, and segmental LAEF., Conclusion: The RT-3DE method may be a feasible and accurate method for evaluating LA volume and function of AF patients in clinical practice.

We report the complete genome sequence of Lactobacillus plantarum CGMCC 8198, a novel probiotic strain isolated from fermented herbage. We have determined the complete genome sequence of strain L. plantarum CGMCC 8198, which consists of genes that are likely to be involved in dairy fermentation and that have probiotic qualities., (Copyright © 2017 Dong et al.)

Objective: To evaluate efficacy and advantages of the Traditional Chinese Medicine (TCM) synthetic rehabilitation therapy in the treatment of wrist dysfunction after distal radius fractures., Methods: From May 2014 to October 2015, 72 patients with distal radius fracture meeting standards were treated using central randomization system for clinical research. All the patients were divided into two groups: 36 patients in test group and 36 in control group. Sixty-nine cases were finished treatment and followed up in the end. The test group fell off 1 case, and the control group fell off 2 cases. The test group was given TCM synthetic rehabilitation (manipulative therapy, joint mobilization, soaking-washing with Chinese medicinal herbs, functional exercise), and the control group was given functional exercise as well as soaking-washing with Chinese medicinal herbs, 3 weeks for both. Five evaluation standards were used in this research, which were grip strength, patient-rated wrist evaluation (PRWE), Gartland and Werley wrist score, self-rating anxiety scale(SAS) and the overall curative effect evaluation. Before treatment(baseline), after 3 weeks of treatment and 3 months after fracture were the three points in time when collected the data., Results: After 3 weeks of treatment and 3 months after fracture, the test group had a significantly better results than those of control group in the PRWE, G-W wrist score and the overall curative effect evaluation( P <0.05). In terms of grip strength recovery, after 3 weeks of treatment, the intergroup difference between the test group and the control group were statistically significant relative to the baseline regarding grip strength of ipsilateral wrist by group t-test( P <0.05). However, the test group and the control group had no statistically significant relative to the baseline at 3 months after fracture in grip strength( P <0.05). For the anxiety of patients, compared with the test group and control group at before and after rehabilitation treatment, the anxiety of both test group and control group cases was eased( P <0.05). However, The degree of anxiety relief in test group and control group cases had no difference( P >0.05)., Conclusions: The TCM synthetic rehabilitation therapy has better curative effects on the treatment of functional disability of wrist joints after distal radius fractures than the general therapy of soaking-washing with Chinese medicinal herbs and functional exercise., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.

Paeonol and danshensu is the representative active ingredient of traditional Chinese medicinal herbs Cortex Moutan and Radix Salviae Milthiorrhizae, respectively. Paeonol and danshensu combination (PDSS) has putative cardioprotective effects in treating ischemic heart disease (IHD). However, the evidence for the protective effect is scarce and the pharmacological mechanisms of the combination remain unclear. The present study was designed to investigate the protective effect of PDSS on isoproterenol (ISO)-induced myocardial infarction in rats and to elucidate the potential mechanism. Assays of creatine kinase-MB, cardiac troponin I and T and histopathological analysis revealed PDSS significantly prevented myocardial injury induced by ISO. The ISO-induced profound elevation of oxidative stress was also suppressed by PDSS. TUNEL and caspase-3 activity assay showed that PDSS significantly inhibited apoptosis in myocardia. In exploring the underlying mechanisms of PDSS, we found PDSS enhanced the nuclear translocation of Nrf2 in myocardial injured rats. Furthermore, PDSS increased phosphorylated PI3K and Akt, which may in turn activate antioxidative and antiapoptotic signaling events in rat. These present findings demonstrated that PDSS exerts significant cardioprotective effects against ISO-induced myocardial infarction in rats. The protective effect is, at least partly, via activation of Nrf2/HO-1 signaling and involvement of the PI3K/Akt cell survival signaling pathway.

Hawthorn is a berry-like fruit from the species of Crataegus. In China, it has another more famous name, Shan-Zha, which has been used to improve digestion as a traditional Chinese medicine or food for thousands of years. Moreover, during the last decades, hawthorn has received more attention because of its potential to treat cardiovascular diseases. However, currently, only fruits of C. pinnatifida and C. pinnatifida var. major are included as Shan-Zha in the Chinese Pharmacopoeia. In this study, our results showed that the ethanol extract of Zhongtian hawthorn, a novel grafted cultivar of C. cuneata (wild Shan-Zha), could markedly reduce body weight and levels of serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, and liver cholesterol of hyperlipidemia mice. It could suppress the stimulation effect of high-fat diet on the transcription of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and p65, and counteract the downregulation of CYP7A1 and LDLR. In addition, the results of luciferase reporter assay and Western blot showed that the transcriptional activity of HMGCR promoter was inhibited by Zhongtian hawthorn ethanol extract in a dose-dependent manner, while overexpression of p65 could reverse this transcriptional repression effect. These results suggested that Zhongtian hawthorn could provide health benefits by counteracting the high-fat diet-induced hypercholesteolemic and hyperlipidemic effects in vivo, and the mechanism underlying this event was mainly dependent on the suppressive effect of Zhongtian hawthorn ethanol extract on the transcription of HMGCR via nuclear factor-kappa B (NF-κB) signal pathway. Therefore, this novel cultivar of hawthorn cultivar which has much bigger fruits, early bearing, high yield, cold resistance, and drought resistance, might be considered as a good alternative to Shan-Zha and has great value in the food and medicine industry. In addition, to our best knowledge, this is also the first report that the extract of Crataegus could suppress the transcription of HMGCR via NF-κB signal pathway., (© 2016 by the Society for Experimental Biology and Medicine.)

Objective: To use Monte Carlo simulation to assess the uncertainty and variability of tobacco consumption through wastewater analysis in a city., Methods: A total of 11 wastewater treatment plants (WWTPs) (serving 2.2 million people; approximately 83% of urban population in Dalian) were selected and sampled. By detection and quantification of principal metabolites of nicotine, cotinine (COT) and trans-3'-hydroxycotinine (OH-COT), in raw wastewater, back calculation of tobacco use in the population of WWTPs can be realised., Results: COT and OH-COT were detected in the entire set of samples with an average concentration of 2.33 ± 0.30 and 2.76 ± 0.91 µg/L, respectively. The mass load of absorbed NIC during the sampling period ranged from 0.25 to 4.22 mg/day/capita with an average of 1.92 mg/day/capita. Using these data, we estimated that smokers in the sampling area consumed an average of 14.6 cigarettes per day for active smoker. Uncertainty and variability analysis by Monte Carlo simulation were used to refine this estimate: the procedure concluded that smokers in Dalian smoked between 10 and 27 cigarettes per day. This estimate showed good agreement with estimates from epidemiological research., Conclusions: Sewage-based epidemiology may be a useful additional tool for the large-scale monitoring of patterns of tobacco use. Probabilistic methods can be used to strengthen the reliability of estimated use generated from wastewater analysis., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Cervical spine manipulation (CSM) is a commonly spinal manipulative therapies for the relief of cervical spine-related conditions worldwide, but its use remains controversial. CSM may carry the potential for serious neurovascular complications, primarily due to vertebral artery dissection (VAD) and subsequent vertebrobasilar stroke. Here, we reported a rare case of locked-in syndrome (LIS) due to bilaterial VAD after CSM treated by arterial embolectomy.A 36-year-old right-handed man was admitted to our hospital with numbness and weakness of limbs after treating with CSM for neck for half an hour. Gradually, although the patient remained conscious, he could not speak but could communicate with the surrounding by blinking or moving his eyes, and turned to complete quadriplegia, complete facial and bulbar palsy, dyspnea at 4 hours after admission. He was diagnosed with LIS. Then, the patient was received cervical and brain computed tomography angiography that showed bilateral VAD. Aortocranial digital subtraction angiography showed vertebrobasilar thrombosis, blocking left vertebral artery, and stenosis of right vertebral artery. The patient was treated by using emergency arterial embolectomy and followed by antiplatelet therapy and supportive therapy in the intensive care unit and a general ward. Twenty-seven days later, the patient's physical function gradually improved and discharged but still left neurological deficit with muscle strength grade 3/5 and hyperreflexia of limbs.Our findings suggested that CSM might have potential severe side-effect like LIS due to bilaterial VAD, and arterial embolectomy is an important treatment choice. The practitioner must be aware of this complication and should give the patients informed consent to CSM, although not all stroke cases temporally related to SCM have pre-existing craniocervical artery dissection.

Surface water samples from the Huangpu River were filtered to measure the UV absorption and fluorescence spectrum. Dissolved organic carbon (DOC), N-nitrosodimethylamine (NDMA), and its formation potential (NDMA-FP) were also analyzed to explore relationships between the properties of dissolved organic matter (DOM) and the formation potential of disinfection byproducts-NDMA in the Huangpu River. The study found that: NDMA-FP concentration increased with the increasing of DOC concentration (r = 0.487, P < 0.01), but it had negative relationships with SUVA254 and HIX (r = -0.605, P < 0.01; r = -0.396, P < 0.01). NDMA-FP concentration had positive relationships with the fluorescence intensity of protein-like substances such as low-molecular-weight (LMW) tyrosine-like and tryptophan-like substances (r = 0.421, P < 0.01; r = 0.426, P < 0.01), but had a negative relationship with humic-like substance (r = -0.422, P < 0.01). Therefore, NDMA formation potential increases with the increasing DOM content in the Huangpu River, which is significantly related with the protein-like substances, but decreases with the increasing aromaticity and humification of DOM.

The aims of this study were to determine the compositions and residual properties of petroleum hydrocarbon in soil, as well as to identify the source and weathering degree of the pollution. A total of 5 producing wells in Gudao and Hekou oil producing region of Shengli oilfields were analyzed. More than 50 individual target compounds including straight-and branched-chain alkanes( n-alkanes, pristine and phytane) and polycyclic aromatic hydrocarbons (PAHs) in soil samples and crude oil were determined by gas chromatography-mass spectrometry (GC-MS). The percentages of chain alkanes and PAHs in total solvent extractable matters(TSEM) of soil samples were both much lower than those in the crude oil samples. The compositions of petroleum hydrocarbon in soil samples differed from those in crude oil, which indicated the n-alkanes with carbon numbers <12 were much easier to lose in contrast to the n-alkanes with high carbon numbers. With n-octadecane/phytane as index for the weathering rate of oil contaminated soils, the relationship between the index and petroleum hydrocarbon compounds was analyzed using principal component analysis (PCA). The results showed that the n-alkanes with carbon numbers > 33 and the PAHs with rings between 3 and 5 were much harder to degrade. PCA of 4 indexes for source identification revealed more than 50% of the soil samples were polluted by crude oil, which needs more attention during remediation.