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Clinical relevance All eye health care practitioners should know how to control myopia. Background Investigating the adjunctive effects of orthokeratology and 0.01% atropine eye drops on controlling the progression of myopia in Chinese children. Methods The prospective study included Chinese children aged 8 to 13 years having a spherical equivalent refractive error ranging from -2.00 to -5.00 D. Participants were categorised into two groups: combination group (orthokeratology and 0.01% atropine) or atropine group (0.01% atropine). The axial length and spherical equivalent refraction were measured at baseline and every three months post-treatment and compared over two years. Results The combinaion and atropine groups comprised 20 and 22 participants. Following two years of treatment, the average spherical equivalent refraction change was 0.88 ± 0.31 D and 1.14 ± 0.63 D in the combination group and atropine group, respectively (P = 0.026), with an average increment in axial length of 0.50 ± 0.17 mm and 0.61 ± 0.21 mm, respectively (P = 0.091). In the atropine group, increased axial length was positively correlated with baseline spherical equivalent refraction (P = 0.018) and negatively correlated with baseline age (P = 0.003). However, these correlations were not observed in the combination group. In the subgroup of subjects aged 8-10 years and another subgroup of subjects with shorter initial axial length (22.00 to 24.50 mm), the changes in axial length over two years were significantly smaller in the combination group than the atropine group. Conclusion Orthokeratology and 0.01% atropine eye drops combination therapy were found to be more effective in reducing progression of myopia, as measured through spherical equivalent refraction changes, than atropine monotherapy in children over two years. Combinatorial therapy was more effective in controlling the elongation of axial length in children with younger baseline age or shorter baseline axial length.

Background Elucidation of the molecular mechanisms involved in the pathogenesis of coronavirus disease 2019 (COVID-19) may help to discover therapeutic targets. Methods To determine the metabolomic profile of circulating plasma from COVID-19 survivors with pulmonary sequelae 3 months after discharge, a random, outcome-stratified case-control sample was analyzed. We enrolled 103 recovered COVID-19 patients as well as 27 healthy donors, and performed pulmonary function tests, computerized tomography (CT) scans, laboratory examinations, and liquid chromatography-mass spectrometry. Results Plasma metabolite profiles of COVID-19 survivors with abnormal pulmonary function were different from those of healthy donors or subjects with normal pulmonary function. These alterations were associated with disease severity and mainly involved amino acid and glycerophospholipid metabolic pathways. Furthermore, increased levels of triacylglycerols, phosphatidylcholines, prostaglandin E2, arginine, and decreased levels of betain and adenosine were associated with pulmonary CO diffusing capacity and total lung capacity. The global plasma metabolomic profile differed between subjects with abnormal and normal pulmonary function. Conclusions Further metabolite-based analysis may help to identify the mechanisms underlying pulmonary dysfunction in COVID-19 survivors, and provide potential therapeutic targets in the future.

Mercury (Hg) pollution is a worldwide concern. Silica nanoparticles (nano-SiO2) can be released into ecosystems through natural and anthropogenic (engineered nano-SiO2) processes. Here, the influence of two sizes (30 nm and 50 nm) of artificial nano-SiO2 on Hg accumulation in soybean plants, the chemical form and distribution of Hg in plant tissues and the levels of chlorophyll and antioxidant enzymes in plants were investigated. The results showed that both sizes of nano-SiO2 amendments alleviated the growth inhibition induced by Hg and reduced the accumulation (62.2–83.6% in roots; 67.9–75.7% in stems; 45.0–70.7% in leaves lower with nano-SiO2 amendments vs. Hg-only exposure) and translocation (transport rates: 0.18–0.19 with nano-SiO2 amendments vs. 0.22–0.26 Hg-only exposure) of Hg in soybean seedlings. Compared with the Hg-only exposed groups, nano-SiO2 amendments significantly reduced the Hg concentrations in the epidermis and pericycle of the roots and stems, especially the pericycle measured by synchrotron radiation X-ray fluorescence (SRXRF). The application of nano-SiO2 also ameliorated the chlorophyll decrease (15.3–50.1% higher with nano-SiO2 amendments vs. Hg-only exposure) and antioxidant enzyme increase (20.7–33.2% lower with nano-SiO2 amendments vs. Hg-only exposure) induced by Hg stress. Additionally, the RS–Hg–SR bonding form in the roots of nano-SiO2 treated groups significantly decreased when compared with that of Hg-only exposed groups, and over 85% of the total Hg content was present in the form of R–Hg–Cl, which was largely consistent with the original Hg exposure species and indicated a low incorporation rate of Hg into plant tissues. This study explored the mechanism of nano-SiO2 against Hg toxicity in plants, and offered a new passivating agent option for Hg remediation.

The objective of the present study was to determine the role of RP11-84C13.1 in osteoporosis (OP) and its molecular mechanism. First, clinical samples were collected from OP patients and normal control patients. Human bone marrow stromal cells (hBMSCs) were extracted from femoral head tissues. Runt-related transcription factor 2 (RUNX2) and RP11-84C13.1 serum levels were assessed by reverse transcription-quantitative (RT-q)PCR. Following transfection of pcDNA-RP11-84C13.1, si-RP11-84C13.1, microRNA (miRNA)-23b-3p mimic and miRNA-23b-3p inhibitor, the expression levels of RUNX2 and RP11-84C13.1 were determined by RT-qPCR. In addition, the osteogenic ability of hBMSCs was assessed by Alizarin Red staining. The binding of RP11-84C13.1 to miRNA-23b-3p and the binding of miRNA-23b-3p to RUNX2 was confirmed by dual-luciferase reporter gene assay. Long non-coding RNA (lncRNA) RP11-84C13.1 was significantly downregulated in the serum of OP patients. The osteogenic differentiation-related genes RUNX2 and RP11-84C13.1 were markedly upregulated in a time-dependent manner, while the miRNA-23b-3p level gradually decreased in hBMSCs with the prolongation of osteogenesis. RP11-84C13.1 knockdown inhibited the osteogenic differentiation of hBMSCs. Furthermore, RP11-84C13.1 regulated RUNX2 expression by targeting miRNA-23b-3p. Overexpression of miRNA-23b-3p partially reversed the promoting effect of RP11-84C13.1 on the osteogenesis of hBMSCs. In conclusion, lncRNA RP11-84C13.1 upregulated RUNX2 by absorbing miRNA-23b-3p, and thus induced hBMSC osteogenesis to alleviate osteoporosis.

The development of medical technology provides medical specialists with a variety of choices for their primary liver cancer patients, including partial liver resection, transcatheter arterial chemoembolization, liver transplantation, and so on. However, in this context, because patients with primary liver cancer frequently do not receive adequate information to help make complicated medical decisions, those patients, who are usually otherwise ignorant about their disease, are facing multiple difficult choices. The problem might be alleviated with a process called "shared decision making." Accordingly, researchers developed a smartphone application named "Shared Decision Making Assistant" for primary liver cancer patients in China, and in this article, we report the process of its development. First, individual interviews were conducted to identify the specific needs and status of primary liver cancer patients participating in shared decision making. Next, expert group discussions were held among primary liver cancer medical experts, nurses, and software engineers, using a decision-making process called the Delphi method, which was used to arrive at a group opinion or decision by surveying a panel of experts, to draft the framework and decide on the contents of the mobile health-based decision aids program. Feedbacks and suggestions were collected to optimize the workflow of "Shared Decision Making Assistant." The resulting application consisted of seven modules: personal information, primary liver cancer treatment knowledge center, decision aids path, continuing care, interactive platform, health education, and backstage management.

We report a case of a young female patient who developed progressive neurological dysfunction with a ring-enhancing tumor-like nodule on brain magnetic resonance imaging. Urgent surgery was performed to remove the mass in the left basal ganglia. Pathological findings showed that the necrotic brain areas were accompanied by congestion, edema, discrete hemorrhage, and intestinal and perivascular lymphohistiocytic infiltration. Immunohistochemical staining results showed that Toxoplasma gondii (T. gondii) immunoreactivity was detected in both cysts and tachyzoites in these areas. The glycerol-3-phosphate dehydrogenase gene (B1) of T. gondii was amplified by sequence-specific polymerase chain reaction (PCR) and the PCR products were bi-directional Sanger sequenced. A 195 bp consensus sequence of the gene B1 was found to be 98% identical to a reference T. gondii sequence (GenBank accession No. kx270373). The final diagnosis was toxoplasmic encephalitis in the left basal ganglia. This report suggests that PCR and bi-directional DNA sequencing of T. gondii gene might be the most convenient and rapid tools for accurate diagnosis of toxoplasmic encephalitis .

Highlights • Recombinant porcine IL-22 has been expressed with activation of STAT3 signal. • pIL-22 reversed apoptosis induced by DON and protected the integrity of epithelial. • pIL-22 defended ETEC K88 infection with increased pBD-1 expression., Pigs suffer enteritis induced by pathogenic bacteria infection and toxins in the moldy feed, which cause intestinal epithelial damage and diarrhea through the whole breeding cycle. Interleukin-22 (IL-22) plays a critical role in maintaining intestinal mucosal barrier function through repairing intestinal epithelial damage. However, little was known about the effects of IL-22 against apoptosis caused by toxins and infection of intestinal pathogens in the intestinal epithelium, especially in pigs. In this study, we had successfully used prokaryotic expression system to produce recombinant porcine interleukin-22. Meanwhile, purified rIL-22 could activate STAT3 signal pathway and have been demonstrated to be safe to IPEC-J2 cells by increasing E-cadherin expression, without proinflammatory cytokines changes. Furthermore, rIL-22 reversed apoptosis induced by deoxynivalenol (DON) and played a vital part in repairing the intestinal injury. We also found that rIL-22 stimulated epithelial cells to secrete pBD-1 against enterotoxigenic E. coli (ETEC) K88 infection, as well as alleviating apoptosis ratio. This study provided a theoretical basis for curing intestinal inflammation caused by ETEC infection and epithelial apoptosis induced by DON with rIL-22 in pigs.

To explore the effects of reducing the Cp levels on intestinal barrier function, low Cp (LP) and NRC standard Cp (NP) diets were fed to pigs from 45 to 160 days, and in vitro experiments were performed using monolayers of IPEC-J2 cells. The number of goblet cells, expression of proteins related to cell junction, amino acid transport, glucose transport, transepithelial electrical resistance (TEER), dextran permeability, and IL-6 secretion level were detected in pigs. The results demonstrated that a moderate reduction of Cp levels did not affect intestinal morphology, as demonstrated by a normal villi height, crypt depth and normal numbers of goblet cells. The maintenance of the intestinal structure obtained with LP was also confirmed by stable mRNA expression levels of muc2 and E-cadherin in the jejunum. We also found that LP did not affect the protein expression of cationic amino acid transporter 1 (CAT-1) and alanine serine cysteine transporter 1 (ASCT1) from 45 to 160 days. Moreover, the excitatory amino acid transporter 3 (EAAT3), sodium-glucose cotransporter 1 (SGLT1) and glucose transporter (GLUT2) protein expression levels in the jejunum were significantly increased at a certain age during the rearing period. Furthermore, we also demonstrated that a reduction in protein concentration up to 15% in the cultural medium of IPEC-J2 cells did not impact the mucosal barrier function. This study demonstrated that a moderate reduction of the protein level did not affect intestinal mucosal barrier function and morphology in the jejunum.

The single and/or combination use of immune checkpoint blockade therapies in human infectious diseases and cancer are rapidly expanding. Despite early efforts, substantial uncertainty remains about the safety and efficacy of immune checkpoint blockade in some populations. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and T-cell immunoglobulin mucin-3 (Tim-3) are the major targetable co-inhibitory receptors on T cells. Here we showed that in animal studies, treatment with either CTLA-4- or Tim-3-blocking antibody caused greater susceptibility to fetal loss with altered cytokine profiles by decidual CD4+T (dCD4+T) cells. CTLA-4 and Tim-3 pathways appeared to play key roles in maintaining maternal-fetal tolerance by regulating the function of dCD4+T cells. In addition, the abnormality in number and functionality of dCTLA-4+Tim-3+CD4+T cells was associated with miscarriage. These findings underscored the important roles of the CTLA-4 and Tim-3 pathways in regulating dCD4+T cells function and maintaining normal pregnancy. Our study also emphasized the importance of careful consideration of reproductive safety when choosing immune checkpoint blockade therapies in real world clinical care.

A unique immunotolerant microenvironment with Th2 bias in the decidua provides an essential security for successful pregnancy. The disorganized maternal-fetal immune tolerance contributes to more than 50% of unexplained recurrent spontaneous abortion (RSA). How the Th2 bias is developed at the maternal-fetal interface remains undefined. NR2F2, a member of steroid/thyroid nuclear receptor superfamily, is endowed with diverse importance in cell-fate specification, organogenesis, angiogenesis, and metabolism. Here, we showed that NR2F2 was absolutely highly expressed in decidual CD4+T(dCD4+T) cells, but not in peripheral circulating CD4+T cells during early pregnancy. Decidual NR2F2-expressing CD4+T cells dominantly produced Th2 cytokines. In unexplained RSA patients, NR2F2 expression in dCD4+T cells was significantly decreased, accompanied with disordered phenotype of dCD4+T cells. Furthermore, overexpression of NR2F2 promoted the Th2 differentiation of naive CD4+T cells. Immunoprecipitation experiment confirmed the binding relationship between GATA-3 and NR2F2, which implied GATA-3 may be an important interactive element involved in the immunoregulatory process of NR2F2. This study is the first to reveal a previously unappreciated role for NR2F2-mediated dCD4+T cells in maternal-fetal immune tolerance and maintenance of normal pregnancy, in the hope of providing a potential biomarker for prediction and prevention of clinical unexplained RSA.

Well-regulated maternal-fetal immune tolerance is a prerequisite for normal pregnancy. Hyperactivated immune cells and overwhelming inflammatory responses trigger adverse gestation outcome, such as recurrent spontaneous abortion (RSA). Local exacerbation of immunomodulatory cells in maternal decidua is a critical event, tightly linked with fetus acceptance. Owning to the notable immunoregulatory potentials, mesenchymal stromal cells (MSCs) and regulatory T cells (Tregs) have been separately reported as promising therapeutic approaches for refractory RSA attributable to certain immune disorders. However, the cross-talk between MSCs and Tregs at the fetal-maternal interface remains poorly understood. Here we revealed, for the first time, that umbilical MSCs could induce expansion of decidual Foxp3+CD4+ T cells with upregulated production of IL-10 and TGF-β. Meanwhile, MSCs reinforced the immune suppressive functions of decidual Tregs (dTregs). More important, MSCs-instructed dTregs gained enhanced capacity to suppress Th1 and Th17 related inflammatory responses. In vivo data demonstrated that adoptive transfer of MSCs obviously promoted accumulation of Foxp3+ dTregs in lipopolysaccharide (LPS)-induced mice abortion model and spontaneous abortion model (DBA/2-mated female CBA/J mice). Furthermore, MSCs treatment effectively ameliorated absorption rate in both models. This study may offer a new insight for the application of MSCs and Tregs in clinical recurrent miscarriage.

Endometritis is an inflammatory disease of the endometrium, which is responsible for endometrial dysfunction, decidualization failure, and increased incidence of early pregnancy loss. SCM-198, a synthetic form of leonurine, is well known to possess anti-inflammatory effects. SCM-198 has been reported to display beneficial effects on endometritis. However, the specific mechanisms of SCM-198 in preventing endometritis remain unknown. In this study, we focused on the molecular mechanism of SCM-198 in inhibiting endometritis. The anti-inflammatory effects and the related signaling pathways of SCM-198 were studied in vitro using human endometrial stromal cells (hESCs). Reverse transcriptase-polymerase chain reaction and western blot analysis results demonstrated that SCM-198 markedly inhibited lipopolysaccharide (LPS)-induced endometrial inflammatory response by suppressing the LPS-JNK-cJUN/cFOS-TLR4-NF-κB pathway. The preventive and therapeutic effects of SCM-198 on endometrial inflammation were explored by using a mouse model of LPS-induced endometritis. SCM-198 produced essentially the same effects when administered either post-treatment (after LPS) or pre-treatment (before LPS) via vaginal or intraperitoneal administration. In vivo results indicated that SCM-198 is a potential effective drug for the treatment of endometritis.

Cuiying Zhang,1 Wei Liu,2 Fei Li,1 Yang Feng,1 Yunyun Li,1 Jia Wang3 1Department of Gynaecology, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Orthopedics, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Gynaecology and Obstetrics, University-Town Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Jia WangDepartment of Gynaecology and Obstetrics, University-Town Hospital of Chongqing Medical University, No. 55 University Town Middle Road, Shapingba District, Chongqing, 401331, People’s Republic of ChinaTel +86 13508307321Fax +86 023-65715700Email hjx104327zcl@163.comBackground: More and more evidences show that circular RNA (circRNA) has an important role in ovarian cancer (OC). Hsa_circ_0015326 is a newly discovered upregulated circRNA in OC, but its role and mechanism in OC have not been studied yet.Methods: Quantitative real-time PCR was used to detect the expression of hsa_circ_0015326, microRNA (miR)-127-3p and MYB. The viability, colony number, cell cycle process, invasion, migration and apoptosis of cells were determined using cell counting kit 8 assay, colony formation assay, flow cytometry, transwell assay and wound healing assay. Moreover, the protein expression levels of metastasis, proliferation, apoptosis markers and MYB were assessed using Western blot analysis. The interaction between miR-127-3p and hsa_circ_0015326 or MYB was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. Xenograft tumors were built to explore the role of hsa_circ_0015326 in OC tumor growth in vivo.Results: Elevated expression of hsa_circ_0015326 was identified in OC tissues and cells. Loss-of-function experiments suggested that silenced hsa_circ_0015326 inhibited the proliferation, invasion, migration, and promoted the apoptosis of OC cells in vitro, as well as inhibited OC tumorigenesis in vivo. Mechanically, hsa_circ_0015326 sponged miR-127-3p and miR-127-3p targeted MYB. The rescue experiments revealed that miR-127-3p inhibitor reversed the inhibitory effect of hsa_circ_0015326 silencing on OC progression, and MYB overexpression reversed the suppressive effect of miR-127-3p on OC progression. In addition, our data indicated that MYB expression was positively regulated by hsa_circ_0015326.Conclusion: This study showed that hsa_circ_0015326 could facilitate OC progression by regulating the miR-127-3p/MYB axis, which suggested that it might become a potential target for the treatment of OC.Keywords: ovarian cancer, hsa_circ_0015326, miR-127-3p, MYB

Purpose To report surgical outcomes of 25-gauge pars plana vitrectomy using air as an internal tamponade for patients with primary rhegmatogenous retinal detachment (RRD). Methods A retrospective clinical study of 59 eyes of 59 consecutive patients presented with primary RRD at the Beijing Tongren Eye Center in China. From August 2016 to May 2018, medical records of the patients who underwent 25-gauge pars plana vitrectomy with air tamponade for RRD were reviewed. The main outcome measures were primary and final anatomical success (retinal re-attachment) rates, and postoperative complications. Results Of the 59 patients, aged 54.47 ± 11.81 years, 31 (52.5%) were men. Vitrectomy was performed 3 to 40 (averaged 16.98 ± 10.17) days after the onset of symptoms, and the mean follow-up period was 12.90 ± 5.92 months (ranging 6.07-26.10 months). Forty-two eyes (71.2%) had RRD with retinal breaks in the superior half of the retina, and the mean number of retinal breaks was 1.75 ± 0.94. Three eyes (5.1%) had RRD with giant retinal tears. Of the 59 eyes, 35 (59.3%) had RRD with inferior quadrants involved. Proliferative vitreoretinopathy (PVR) gradings were C1 in 2 (3.4%) eyes and B or below in 57 (96.6%) eyes. The primary and final anatomical success rates were 94.9% (56/59) and 98.3% (58/59), respectively. Of the three eyes which developed re-detachment of the retina, one eye had postoperative progression of PVR and two eyes were RRD associated with macular hole in high myopia. Postoperative complications included 5 eyes (8.5%) with serous choroidal detachment within 3 days after surgery and 4 eyes (6.8%) with macular epiretinal membrane formation 1 to 8 months after surgery. Secondary cataract surgery was performed in 13 of the 53 phakic eyes (24.5%) during follow-up. Conclusion Small-gauge pars plana vitrectomy with air tamponade may be effective in treating selected cases of relatively simple primary RRD. Additional studies are needed to verify the efficacy of this surgical approach for more complicated cases such as those with giant retinal tears.

Our study was aimed to investigate the mechanism of rs4759314 located in HOTAIR involved in congenital heart disease. Luciferase assay was performed to evaluate whether rs4759314 affected the transcription efficiency of HOTAIR promoter, and confirm miR-545 target gene. Real-time PCR, Western-blot and IHC were carried out to investigate the relationship among HOTAIR, EGFR, p-ERK, P-P38 MAPK. MTT assay and flow cytometry analysis were performed to detect the effect of HOTAIR on cell viability and apoptosis. The presence of G allele of the polymorphism located in HOTAIR promoted transcription activity of HOTAIR promoter. Furthermore, HOTAIR inhibited miR-545 expression. EGFR was identified as a virtual target gene of miR-545 using bioinformatics analysis, and miR-545 apparently decreased luciferase activity of wild-type EGFR 3'UTR, while miR-545 had no effect on luciferase activity of mutant EGFR 3'UTR. HOTAIR and EGFR were lowly expressed, while miR-545 was highly expressed in VSD group. Higher levels of HOTAIR and ECFR, while a lower level of miR-545 were observed in AG than AA groups. Regulatory relationships between HOTAIR and miR-545, as well as EGFR and miR-545 were found to be negatively correlated, with the negative correlation coefficient being -0.49 and -0.46, respectively. HOTAIR evidently increased EGFR p-ERK and P-P38 MAPK expression levels, moreover HOTAIR substantially promoted cell viability, and inhibited cell apoptosis. In this study, we suggested the possible relation between the rs4759314 polymorphism and the risk of congenital heart disease, and explored the deregulation of HOTAIR/miR-545/EGFR/MAPK signaling pathway in the pathogenesis of congenital heart disease.

MicroRNAs serve a crucial role in the regulation of malignant biological behavior of Ewing's sarcoma (ES). Abnormal expression of miR-107 has been reported in a cohort of cancers, while its exact function in ES remains unclear. Hence, we explored the expression of miR-107 in ES cells and detected its effects on the malignant phenotype of ES cells. Firstly, we perceived the under-expression of miR-107 in human ES cells contrast with the human mesenchymal stem cells. Over-expression of miR-107 restrained cell proliferation and tube formation, arrested cell cycle progression, and facilitated cell apoptosis in SK-ES-1 and RD-ES cell lines. Furthermore, hypoxia inducible factor-1β (HIF-1β) was assumed as a target gene of miR-107. We confirmed the target role of HIF-1β in ES cells. Finally, restoring the expression of HIF-1β could partly abolish miR-107-mediated tumor suppression in ES cells. In conclusion, our results advised that miR-107 suppressed the malignant biological ability of ES cells through targeting HIF-1β.

// Yunyun Li 2 , Gaohai Shao 1 , Minghua Zhang 1 , Fengchen Zhu 1 , Bo Zhao 1 , Chao He 1 , Zhongzu Zhang 1 1 Department of Orthopedics, the Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, PR China 2 Department of Gynecology and Obstetrics, the Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, PR China Correspondence to: Zhongzu Zhang, email: zhangzhongzu@126.com Keywords: Ewing sarcoma, miR-124, SLUG, cyclin D2, mesenchymal features Received: December 03, 2016 Accepted: December 12, 2016 Published: December 31, 2016 ABSTRACT Metastasis is the most powerful predictor of poor outcome of Ewing sarcoma (ES). Thus, identification of new molecules involved in tumor metastasis is of crucial importance to reduce morbidity and mortality of this devastating disease. In this study, we found that miR-124, a highly conserved miRNA, was suppressed in ES tissues and might be associated with tumor metastasis through suppressing its mesenchymal features. Overexpression of miR-124 suppressed the invasion of ES cells in vitro and tumor metastasis in vivo , which might be achieved through suppressing its mesenchymal features, as overexpression of miR-124 could repress the mesenchymal genes expression, and inhibit cell differentiation to mesenchymal lineages in ES cells. However, when SLUG was experimentally restored in these cells, mesenchymal features including suppressed expression of mesenchymal genes and decreased invasive ability were observed. We also found that cyclin D2 (CCND2) was a novel target gene of miR-124, and was directly involved in miR-124-mediated suppressive effects on cell growth. Lastly, we found that treatment with 5-Aza-CdR restored the expression of miR-124, accompanied with suppressed cell proliferation, invasion and mesenchymal features of ES cells, which demonstrated that hypermethylation might be involved in the regulation of miR-124 expression. Collectively, our data suggest that hypermethylation-mediated suppression of miR-124 might be involved in the tumor initiation and metastasis through suppressing the mesenchymal features of ES cells.

Pyroptosis is a form of cell death that is uniquely dependent on caspase-1. Pyroptosis involved in oxidized low-density lipoprotein (ox-LDL)-induced human macrophage death through the promotion of caspase-1 activation is important for the formation of unstable plaques in atherosclerosis. The mitochondrial outer membrane protein NIX directly interacts with microtubule-associated protein 1 light chain 3 (LC3). Although we previously showed that NIX-mediated mitochondrial autophagy is involved in the clearance of damaged mitochondria, how NIX contributes to ox-LDL-induced macrophage pyroptosis remains unknown. Here, immunoperoxidase staining Nix expression decreased in human atherosclerosis. When we silenced NIX expression in murine macrophage cell, active caspase-1, and mature interleukin-1β expression levels were increased and LC3 was reduced. In addition, LDH release and acridine orange and ethidium bromide staining indicated that damage to macrophage cell membranes induced by ox-LDL was substantially worse. Moreover, intracellular reactive oxygen species and NLRP3 inflammasome levels increased. Taken together, these results demonstrated that NIX inhibits ox-LDL-induced macrophage pyroptosis via autophagy in atherosclerosis.

Precipitation is the primary source of water available to vegetation. Although many studies have explored the spatially heterogeneous relationship between vegetation and precipitation, it remains unknown why different precipitation levels lead to comparable vegetation growth and the same precipitation level leads to different vegetation growth. Here we provided a simple, new parameterized calculation method to describe the precipitation-vegetation relation. The new method characterizes the ability of local precipitation to supply the water needed for vegetation growth. In the case of China, the method can explain vegetation growth better than the common indices that represent water supply, such as the SPEI, the PDSI, and soil moisture. We further explored what induces the differences in the capacity of soil to redistribute local precipitation for vegetation growth by examining the sensitivity of the residual value between actual vegetation growth and theoretical precipitation-determined vegetation growth to water storage-related soil properties. Our results indicate that soil texture and soil depth to bedrock rather than climatic factors predicted the above mentioned residual values, which implies that soil water storage capacity can increase or decrease the amount of local precipitation needed for vegetation growth. Soil physical properties that involve a high clay content and a thickness between 1 and 3 m are favorable for the stored precipitation fraction for vegetation growth. Neglecting this effect of soil water storage capacity may introduce inaccuracies when simulating the impact of future climate change on vegetation growth.

Reservoirs are well known as a far-reaching human modification on the functions of natural river networks. However, changes in the chemistry and reactivity of dissolved organic matter (DOM) responding to hydrological management for water retention structures, and its influence on the river carbon cycle, remain poorly understood. Here we show that hydrological management does shape the molecular composition of DOM in the world's largest Three Gorges Reservoir, as revealed by optical spectroscopy and ultrahigh-resolution mass spectrometry. Relatively higher terrestrial input, molecular complexity, isomeric complexity, and environmental stability of DOM were observed during the storage period, whereas the inverse occurred during the drainage period. The results demonstrate that the hydrodynamic processes, which are mainly controlled by water intrusion from mainstream to tributaries, are likely the underlying mechanism controlling DOM chemistry. Integrated with observations from worldwide river reservoirs, the DOM degradation experiments suggest that reservoir hydrological management would enhance DOM mineralization, thereby increase CO2 emission and change the river carbon cycle.

BACKGROUND The aim of this study was to investigate duplication of the vertebral artery (VA) using three-dimensional time-of-flight (3D TOF) magnetic resonance angiography (MRA) in a large study population to further our understanding of vascular variations. MATERIAL AND METHODS A retrospective analysis of 3D TOF-MRA data in 12 826 cases was performed. The occurrence rate of VA duplication was calculated and accompanied vascular anomalies were recoded. RESULTS Twenty-one VA duplication patients were found, with an occurrence rate of 0.164%; 12 of them had left VA duplication with 2 branches initially arising from the aortic arch and left subclavian artery; 9 of them were right VA duplication with the branches originating from the right subclavian artery. In the 21 cases, 11 had other vascular abnormalities. CONCLUSIONS VA duplication is very rare and often associated with other vascular abnormalities. 3D TOF-MRA can accurately display the duplication variation. Better understanding of the variation is instrumental for disease diagnosis, interventional therapy, and surgical operation.

Sweet potato starch (SPS) granules were firstly subjected to heat-moisture treatment (HMT) and then esterified with citric acid (CA). The physicochemical properties of CA-starch and heat moisture treatment citric acid starch (HMT-CA-starch) were investigated. Results showed that the high dosage of CA significantly increased the degree of substitution (DS) and the resistant starch (RS) content of the CA-starch (P

Oxidized low-density lipoprotein (Ox-LDL)-induced macrophage pyroptosis is critical in atherosclerosis inflammation and plaque instability. It has been reported that mitochondrial (mt)DNA-depleted (rho0) cells demonstrate resistance to apoptosis. However, little is known about the susceptibility of rho0 cells to Ox-LDL-induced macrophage pyroptosis. Pyroptosis, a caspase-1-dependent programmed cell death, which compromises membrane integrity, cleaves pro-interleukin (IL)‑1β and pro‑IL‑18 into IL‑1β and IL‑18, respectively and releases damage‑associated molecular pattern molecules, is triggered by a variety of stimuli, including Ox‑LDL. In the present study, the expression levels of cleaved caspase‑1 and IL‑1β in Ox‑LDL‑treated J774A.1 rho0 cells were observed to be significantly decreased when compared with Ox‑LDL‑treated J774A.1 normal cells. Furthermore, J774A.1 rho0 cells exhibited a significant reduction in the ratios of dead cells and lactate dehydrogenase release following Ox‑LDL stimulation compared with the J774A.1 normal cells. In addition, the loss of mtDNA did not influence Ox‑LDL‑induced cholesterol accumulation in J774A.1 rho0 cells, which was observed by Oil Red O staining and CHOD‑PAP assay. Finally, J774A.1 rho0 cells exhibited reduced reactive oxygen species (ROS) production and were capable of maintaining the mitochondrial membrane potential following Ox‑LDL treatment. Thus, the results indicate that the loss of mtDNA potentially rendered murine macrophage J774A.1 resistant to Ox‑LDL‑induced pyroptosis by mitigating NACHT, LRR and PYD domains-containing protein 3 inflammasome activation through reducing ROS production. In addition, mtDNA depletion did not interrupt Ox-LDL-induced intracellular lipid accumulation and continued to maintain the mitochondrial membrane potential.

B-cell epitope is a group of residues which is on the surface of an antigen. It invokes humoral responses. Locating B-cell epitope is important for effective vaccine design, and the development of diagnostic reagents. Mimotope-based B-cell epitope prediction method is a kind of conformational B-cell epitope prediction, and the core idea of the method is mapping the mimotope sequences which are obtained from a random phage display library. However, current mimotope-based B-cell epitope prediction methods cannot maintain a high degree of satisfaction in the circumstances of employing only mimotope sequences. In this study, we did a multi-perspective analysis on parameters for conformational B-cell epitopes and characteristics between epitope and mimotope on a benchmark datasets which contains 67 mimotope sets, corresponding to 40 unique complex structures. In these 67 cases, there are 25 antigen-antibody complexes and 42 protein-protein interactions. We analyzed the two parts separately. The results showed the mimotope sequences do have some epitope features, but there are also some epitope properties that mimotope sequences do not contain. In addition, the numbers of epitope segments with different lengths were obviously different between the antigen-antibody complexes and the protein-protein interactions. This study reflects how similar do mimotope sequence and genuine epitopes have; and evaluates existing mimotope-based B-cell epitope prediction methods from a novel viewpoint.

Osteosarcoma (OS) is the most common primary bone malignancy among children and adolescents. Deregulation of microRNAs has been well documented in OS, while the putative effects of miR‑186 have not been identified yet. In the present study, we assessed the expression of miR‑186 in a cohort of 40 OS tissues and explored its effects on OS cells. As expected, miR‑186 was suppressed in OS tissues compared with relative normal tissues. Overexpression of miR‑186 inhibited cell proliferation, arrested the cell cycle progression and suppressed the cell invasion of the HOS and U2 OS cell lines. These results indicated the tumor‑suppressive role of miR‑186 in OS. Among the target genes of miR‑186, we found that pituitary tumor transforming gene 1 (PTTG1) may be a target gene of miR‑186 in OS and that the overexpression of PTTG1 could partially abolish miR‑186‑mediated suppressive effects on OS cells. Aerobic glycolysis is the major way of energy supply and is one of the characteristic phenotypes of tumor cells. In addition, we found that overexpression of miR‑186 significantly suppressed the expression of hypoxia‑inducible factor 1 (HIF‑1) and inhibited the glucose uptake and lactate production of OS cells. Collectively, our findings demonstrated that miR‑186 functions as a tumor suppressor in OS cells partially by targeting PTTG1 and that HIF‑1‑mediated suppression of aerobic glycolysis may be also involved in its suppressive effects.

Ewing sarcoma (EWS) is a kind of aggressive tumor of bone and soft tissues, which most occurring in children and adolescents. MicroRNAs (miRNAs) perform essential function in the progression and development of EWS, while the putative role of miR-638 in EWS remains uncertain. Accordingly, we detected the expression of miR-638 and explored its putative biological effects on the malignant phenotype of EWS cells. As expected, miR-638 was significantly down-regulated in EWS cells. Moreover, overexpression of miR-638 suppressed cell growth, induced cell apoptosis, and inhibited tubule formation of EWS cells in vitro. Among the putative target genes of miR-638 predicted by the miRNA target prediction tools, vascular endothelial cell growth factor A (VEGFA) attracted out attention most. The luciferase reporter assays reaffirmed that VEGFA was a targeted gene of miR-638 in EWS cells. Furthermore, miR-638 suppressed the mRNA and protein level of VEGFA, and restored the expression of VEGFA reversed the suppressed effects of miR-638 in EWS cells. Taken together, the results suggested that miR-638 might perform tumor suppressive effects in EWS, which might be mediated, at least partially, through suppressing the activity of VEGFA.

The aim of this study was to assess the long-term effects of community-based health management on elderly diabetic patients using a Markov model. A Markov decision model was used to simulate the natural history of diabetes. Data were obtained from our randomized trials of elderly with type 2 diabetes and from the published literature. One hundred elderly patients with type 2 diabetes were randomly allocated to either the management or the control group in a one-to-one ratio. The management group participated in a health management program for 18 months in addition to receiving usual care. The control group only received usual care. Measurements were performed on both groups at baseline and after 18 months. The Markov model predicted that for every 1000 diabetic patients receiving health management, approximately 123 diabetic patients would avoid complications, and approximately 37 would avoid death over the next 13 years. The results suggest that the health management program had a positive long-term effect on the health of elderly diabetic patients. The Markov model appears to be useful in health care planning and decision-making aimed at reducing the financial and social burden of diabetes.

The present study was aimed to investigate the effects of the long non-coding RNA DQ786243 in the regulation of Treg cells in oral lichen planus (OLP), as well as to evaluate its potential molecular mechanisms. Here we found that the expression of DQ786243 and Foxp3 were both overexpressed in the CD4+ cells from the peripheral blood of OLP patients, and their expression was positively correlated. Meanwhile, compared with the normal CD4+ cells, the frequency of Foxp3+ Treg cells in the OLP CD4+ cells was significantly higher. DQ786243 overexpression in normal CD4+ cells resulted in the upregulation of Foxp3 and the higher frequency of Foxp3+ Treg cells. Furthermore, we found that the induction of Foxp3+ Treg cells by DQ786243 significantly increased its suppressive function, and suppressed the function of other CD4+ T cells such as Th1 and Th17 by decreasing the levels of IFN-γ and IL-17. Moreover, we found that DQ786243 overexpression markedly elevated the expression of miR-146a via regulating Foxp3, and thus inhibiting the NF-κB signaling. In conclusion, these findings indicate that DQ786243 may regulate the induction and function of CD4+ Treg cells through Foxp3-miR-146a-NF-κB axis, implicating a novel insight into understanding the progression of OLP.

The objective of this study was to evaluate the health status and associated factors of the elderly Chinese population. A cross-sectional survey was administered to 849 elderly people aged 60 years and over living in a certain district of Nanjing, China. A health rating scale based on the characteristics of the elderly in China was used. The difference of self-rated health between different groups was tested using an ANOVA, and the associated factors were tested using an ordinal logistic regression. The results showed that the general health of the elderly Chinese people studied was not good. The scores of body function, self-care ability, and physical health decreased gradually with age. The scores of men were higher than those of women in terms of emotional personality. The factors associated with the health status of the elderly were education, living mode and marital status. The health status of the elderly Chinese and the associated factors highlighted in this study demonstrated that emotional and social support were more important than financial support for promoting the mental health of the elderly. These findings will provide a basis for the development of programmes promoting the health management and healthy ageing of the elderly in China.

// Yunyun Li 1, * , Zhongzu Zhang 2, * , Zhenghua Xiao 1 , Ying Lin 1 , Tangshu Luo 1 , Qin Zhou 3 , Xiaojing Zhang 1 1 Department of Gynecology and Obstetrics, The Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, PR China 2 Department of Orthopedics, The Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, PR China 3 Department of Gynecology and Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China * These authors contributes to this work Correspondence to: Qin Zhou, email: zhouqin_doctor@126.com Xiaojing Zhang, email: zhangxj_gyn@163.com Keywords: cervical cancer, miR-29b, STAT3, chemotherapy, EMT Received: November 14, 2016 Accepted: January 11, 2017 Published: January 19, 2017 ABSTRACT Radiotherapy combined with platinum-based chemotherapy is the standard-of-care of locally advanced cervical cancer (CC) patients, while nearly 50% of patients do not respond to standard chemotherapy. Thus, identification of relative molecules participated in chemotherapy might provide new insights in the treatment of CC. In this study, we found a cohort of miRNAs were dysregulated upon treatment with cisplatin, among of which miR-29b was the most upregulated one. We further detected its expression in CC tissues, and found that miR-29b was significantly suppressed in CC and its precancerous lesions, HSIL tissues, and was negatively related with tumor invasion. However, upon treatment with cisplatin, the expression of miR-29b was significantly up-regulated. The biological function assays showed that overexpression of miR-29b suppressed the invasion, EMT procedure and angiogenesis of cervical cancer cells in vitro and inhibited tumor growth and neovascularization in vivo through targeting STAT3 signal pathway. While, inhibition of miR-29b could prevent the cisplatin-induced epithelial features, cell movement and angiogenesis of CC cells, which means miR-29b/STAT3 axis participates in the chemotherapy of cisplatin in CC. Collectively, our data suggest that chemotherapy-mediated miR-29b expression participates in the initiation and progression of cervical cancer through suppressing the proliferation, EMT procedure and angiogenesis of cervical cancer cells by targeting STAT3 signal pathway.

The interaction between tumors cells, tumor-derived humoral factors and the bone marrow in the bone niches has been shown to be essential for bone tumor initiation and promotion. Among the tumor stromal cells, tumor-associated macrophages (TAMs) are usually the most abundant immune population. Previously, we reported that let-7a functions as a tumor suppressor in ES. Herein, we found that the suppressive effects are not only limited on the malignant phenotype of tumor cells but also on the regulation of macrophage infiltration. We observed that the let-7a expression is negatively related to macrophage infiltrations in ES. Moreover, overexpression of putative ts-miRNA let-7a significantly suppressed the recruitment of PBMCs in vitro and decreased the macrophage infiltrations in ES-xenografted tumors in vivo. Most importantly, a positive regulatory feedback loop consisting of let-7a, signal transducer and activator of transcription 3 (STAT3), and nuclear factor-kappa B (NF-κB) (let-7a/STAT3/NF-κB) was involved in let-7a-mediated suppressive effects. These data might provide evidence of a novel intracellular signaling network function in ES pathogenesis, and manipulating this novel feedback loop will have therapeutic potential for ES patients.

Although HBV, liver function and tumor characteristics were proven as hepatocellular carcinoma (HCC) prognosis-related, no large-scale and long-term follow-up studies have ever given robust evidence about prognosis predictive effect and contribution to different stage of postoperation. In this study, we evaluated the influence of above index on overall survival (OS) and disease-free survival (DFS) and other clinical data in a rather large population and long-term follow-up. Our study consisted of 1,326 HCC patients who underwent radical resection from 1996 to 2010. Epidemiology, clinical and prognosis data were analyzed. Risk factors of OS and DFS were explored. Cumulative survival comparison between groups was performed with log-rank. Multivariate analysis for independent prognostic factors was determined by Cox proportional hazards model. HBsAg status was a universal factor of HCC recurrence, while preoperational albumin (ALB) and portal vein tumor thrombus (PVTT) affected survival during the whole lifetime. Early stage recurrence was associated with capsule intact [OR (95 %) = 1.54,1.12-2.12, p = 0.009], preoperational alpha-fetoprotein (AFP), TNM and BCLC stages were the most important prognosis factors of recurrence in the early 5 years and PVTT affected the rest time. Survival was mainly associated with tumor characteristic and ALB. Short-time survival was affected with age and AFP, while BCLC was related with the long-time survival. We confirmed that during different periods after resection, factors affecting prognosis did not remain unchanged. Liver function and tumor characteristic affected DFS and OS the whole time, especially the early recurrence. However, HBV infection situation was associated with later recurrence. PVTT showed an opposite effect between early and later recurrence.

There is increasing evidence that oxidative stress is an important risk factor for arsenic-related diseases. Peripheral blood leukocytes constitute an important defense against microorganisms or pathogens, while the research on the impact of chronic arsenic exposure on peripheral blood leukocytes is much more limited, especially at low level arsenic exposure. The purpose of the present study was to explore whether chronic arsenic exposure affects oxidative stress of peripheral blood leukocytes and possible linkages between oxidative stress and arsenic-induced skin lesions. 75 male inhabitants recruited from an As-endemic region of China were investigated in the present study. The classification of arsenicosis was based on the degree of skin lesions. Arsenic levels were measured in drinking water and urine by Atomic Fluorescence Spectroscopy. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was tested by Enzyme-Linked Immunosorbent Assay. 8-OHdG of peripheral blood leukocytes was evaluated using immunocytochemical staining. 8-OHdG-positive reactions were only present in polymorphonuclear leukocytes (PMNs), but not in monocytes (MNs). The 8-OHdG staining of PMN cytoplasm was observed in all investigated populations, while the 8-OHdG staining of PMN nuclei was frequently found along with the elevated amounts of cell debris in individuals with skin lesion. Urinary arsenic levels were increased in the severe skin lesion group compared with the normal group. No relationship was observed between drinking water arsenic or urine 8-OHdG and the degree of skin lesions. These findings indicated that the target and persistent oxidative stress in peripheral blood PMNs may be employed as a sensitive biomarker directly to assess adverse health effects caused by chronic exposure to lower levels of arsenic.

Objects: To investigate the effect of health management on the Chinese elderly. Methods:600 individuals who aged 60 and older in Nanjing, China were randomly allocated into intervention and control group. Results: after 6 month of health management the intervention group elderly improved a lot in the main indexes of health literacy — health knowledge, health behavior, health belief and health skills. As for health services utilization, the hospitalization days reduced between the two groups had significant difference; the times reduced of outpatient in the last 6 months of intervention group was more than the control group, but difference was not statistically significant. The Es of health management are the most were between 0.11 and 0.48 in addition to health knowledge, hyperlipemia patients triglyceride whose Es were greater than 0.5, moderate-intensity interventions. Conclusion: health management play an active role in raising health awareness, chronic diseases prevention of the elderly.