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KCNH6 has been proven to affect glucose metabolism and insulin secretion both in humans and mice. Further study revealed that Kcnh6 knockout (KO) mice showed impaired glucose tolerance. However, the precise function of KCNH6 in the liver remains unknown. Mitochondria have been suggested to maintain intracellular Ca2+ homeostasis; ROS generation and defective mitochondria can cause glucose metabolism disorders, including type 2 diabetes (T2D). Here, we found that Kcnh6 attenuated glucose metabolism disorders by decreasing PEPCK and G6pase abundance and induced Glut2 and IRS2 expression. Overexpression of Kcnh6 increased hepatic glucose uptake and glycogen synthesis. Kcnh6 attenuated intracellular and mitochondrial calcium levels in primary hepatocytes and reduced intracellular ROS and mitochondrial superoxide production. Kcnh6 suppressed oxidative stress by inhibiting mitochondrial pathway activation and NADPH oxidase expression. Experiments demonstrated that Kcnh6 expression improved hepatic glucose metabolism disorder through the c-Jun N-terminal kinase and p38MAPK signaling pathways. These results were confirmed by experiments evaluating the extent to which forced Kcnh6 expression rescued metabolic disorder in KO mice. In conclusion, KCNH6 enhanced hepatic glucose metabolism by regulating mitochondrial Ca2+ levels and inhibiting oxidative stress. As liver glucose metabolism is key to T2D, understanding KCNH6 functions may provide new insights into the causes of diabetes.

ObjectiveDeep venous thrombosis (DVT) of the lower extremity is a common perioperative complication of femoral intertrochanteric fracture. This study aimed to identify the risk factors of lower extremity deep vein thrombosis (DVT) in elderly femoral intertrochanteric fracture patients and establish a nomogram model.MethodsFrom August 2014 to June 2021, a total of 1,652 femoral intertrochanteric fracture patients over the age of 65 were enrolled in our study. We distinguished independent risk factors by univariate and multivariate Cox analyses. A nomogram model was then built, and the discriminative and calibration of the model was evaluated through receiver operating characteristics (ROC) and calibration plots.ResultsA total of 378 patients developed DVT (292 in the training group, 86 in the validation group) while the remaining patients did not. According to the univariate and multivariate Cox analyses results, age (OR = 1.07, 95% CI: 1.04–1.10), fibrinogen (OR = 2.09, 95% CI: 1.68–2.60), D-dimer (OR = 1.33, 95% CI: 1.27–1.40), time from injury to admission (OR = 1.78, 95% CI: 1.55–2.05), functional status (OR = 4.21, 95% CI: 2.86–6.20), and diabetes (OR = 1.65, 95% CI: 1.10–2.48) were identified as independent risk factors of DVT. The ROC values for DVT of the training and validation group were 0.862 and 0.912, and the P-value of the Hosmer-Lemeshow calibration test was 0.767.ConclusionThis nomogram model can be used to predict the probability of preoperative DVT in elderly patients with femoral intertrochanteric fracture and guide physician in perioperative thrombosis management.

Genome-wide association studies for neuromyelitis optica spectrum disorder (NMOSD) have established an association between HLA-DQ alpha 1 (DQA1) and risk for NMOSD. Though ethnicity is generally considered a major influencing factor in genetic analyses, little is known regarding the association of HLA-DQA1 polymorphisms with NMOSD in the Han population, especially the single-nucleotide polymorphisms (SNPs) at HLA-DQA1 .We genotyped SNP at loci rs28383224 in a case-control study consisting of 137 subjects (51 patients with NMOSD and 86 unrelated controls were recruited) of Han ethnicity. Logistic regression was used to test the association of SNP with NMOSD susceptibility, the sex and age were adjusted, odds ratios and 95% confidence intervals were estimated.The rs28383224 polymorphism and susceptibility to NMOSD were not statistically associated ( P0.05) in the Han population in the current study. No significant difference was found in allelic frequencies or genotypic distributions among different subsets of NMOSD patients ( P0.05).In the current study, there is no evidence that polymorphism of rs28383224 in the HLA-DQA1 gene is associated with the risk of NMOSD in the Han Chinese population.

BACKGROUND Hepatic stellate cells (HSCs) are the key effector cells mediating the occurrence and development of liver fibrosis, while aerobic glycolysis is an important metabolic characteristic of HSC activation. Transforming growth factor-β1 (TGF-β1) induces aerobic glycolysis and is a driving factor for metabolic reprogramming. The occurrence of glycolysis depends on a high glucose uptake level. Glucose transporter 1 (GLUT1) is the most widely distributed glucose transporter in the body and mainly participates in the regulation of carbohydrate metabolism, thus affecting cell proliferation and growth. However, little is known about the relationship between TGF-β1 and GLUT1 in the process of liver fibrosis and the molecular mechanism underlying the promotion of aerobic glycolysis in HSCs. AIM To investigate the mechanisms of action of GLUT1, TGF-β1 and aerobic glycolysis in the process of HSC activation during liver fibrosis. METHODS Immunohistochemical staining and immunofluorescence assays were used to examine GLUT1 expression in fibrotic liver tissue. A Seahorse extracellular flux (XF) analyzer was used to examine changes in aerobic glycolytic flux, lactate production levels and glucose consumption levels in HSCs upon TGF-β1 stimulation. The mechanism by which TGF-β1 induces GLUT1 protein expression in HSCs was further explored by inhibiting/promoting the TGF-β1/mothers-against-decapentaplegic-homolog 2/3 (Smad2/3) signaling pathway and inhibiting the p38 and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. In addition, GLUT1 expression was silenced to observe changes in the growth and proliferation of HSCs. Finally, a GLUT1 inhibitor was used to verify the in vivo effects of GLUT1 on a mouse model of liver fibrosis. RESULTS GLUT1 protein expression was increased in both mouse and human fibrotic liver tissues. In addition, immunofluorescence staining revealed colocalization of GLUT1 and alpha-smooth muscle actin proteins, indicating that GLUT1 expression was related to the development of liver fibrosis. TGF-β1 caused an increase in aerobic glycolysis in HSCs and induced GLUT1 expression in HSCs by activating the Smad, p38 MAPK and P13K/AKT signaling pathways. The p38 MAPK and Smad pathways synergistically affected the induction of GLUT1 expression. GLUT1 inhibition eliminated the effect of TGF-β1 on HSC proliferation and migration. A GLUT1 inhibitor was administered in a mouse model of liver fibrosis, and GLUT1 inhibition reduced the degree of liver inflammation and liver fibrosis. CONCLUSION TGF-β1 induces GLUT1 expression in HSCs, a process related to liver fibrosis progression. In vitro experiments revealed that TGF-β1-induced GLUT1 expression might be one of the mechanisms mediating the metabolic reprogramming of HSCs. In addition, in vivo experiments also indicated that the GLUT1 protein promotes the occurrence and development of liver fibrosis.

Disturbed blood flow induces endothelial pro-inflammatory responses that promote atherogenesis. Nanoparticle-based therapeutics aimed at treating endothelial inflammation in vasculature where disturbed flow occurs may provide a promising avenue to prevent atherosclerosis. By using a vertical-step flow apparatus and a microfluidic chip of vascular stenosis, herein, it is found that the disk-shaped versus the spherical nanoparticles exhibit preferential margination (localization and adhesion) to the regions with the pro-atherogenic disturbed flow. By employing a mouse model of carotid partial ligation, superior targeting and higher accumulation of the disk-shaped particles are also demonstrated within disturbed flow areas than that of the spherical particles. In hyperlipidemia mice, administration of disk-shaped particles loaded with hypomethylating agent decitabine (DAC) displays greater anti-inflammatory and anti-atherosclerotic effects compared with that of the spherical counterparts and exhibits reduced toxicity than "naked" DAC. The findings suggest that shaping nanoparticles to disk is an effective strategy for promoting their delivery to atheroprone endothelia.

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BACKGROUND Dubin-Johnson syndrome (DJS) is a benign autosomal recessive liver disease involving mutations of the ABCC2 gene. It is characterized by chronic or intermittent conjugated hyperbilirubinemia, with chronic idiopathic jaundice as the main clinical manifestation. Genetic alterations of the ABCC2 gene are commonly used for diagnosing DJS; however, the causative ABCC2 point mutation in Chinese patients remains unknown. Research on ABCC2 mutations in Chinese DJS patients is extremely rare, and the diagnosis of DJS remains limited. The routine analysis of ABCC2 mutations is helpful for the diagnosis of DJS. Here, we report the clinical characteristics and ABCC2 genotype of an adult female DJS patient. This article is to expound the discovery of more potentially pathogenic ABCC2 variants will that contribute to DJS identification. CASE SUMMARY This study investigated a woman referred for DJS and involved clinical and genetic analyses. ABCC2 mutations were identified by next-generation sequencing (NGS). The patient showed intermittent jaundice and conjugated hyper-bilirubinemia. Histopathological examinations were consistent with the typical phenotype of DJS. Genetic diagnostic analysis revealed an ABCC2 genotype exhibiting a pathogenic variant, namely c.2443C>T (p.Arg815*), which has not been reported previously in the domestic or foreign literature. CONCLUSION Pathogenic ABCC2 mutations play an important role in the diagnosis of DJS, especially in patients with atypical presentations. Currently, NGS is used in the routine analysis of DJS cases and such tests of further cases will better illuminate the relationship between various genotypes and phenotypes of DJS.

Objective To explore the activity changes in neurology clinical practice that have occurred in tertiary public hospitals during the COVID-19 pandemic. Methods Outpatient and inpatient data from the neurology department were extracted from the electronic medical record system of three tertiary Grade A hospitals in Wenzhou. Data were analyzed across 5 months following the beginning of the pandemic (from January 13 to May 17) and compared with the same period in 2019. Data on reperfusion therapy for acute infarction stroke were extracted monthly from January to April. Results The number of outpatients declined from 102,300 in 2019 to 75,154 in 2020 (26.54%), while the number of inpatients in the three tertiary Grade A hospitals decreased from 4641 to 3437 (25.94%). The latter trend showed a significant drop from the 3rd week to the 7th week. The number of patients in these hospitals decreased significantly, and a significant drop was seen in the neurology department. As usual, stroke was the most common disease observed; however, anxiety/depression and insomnia increased dramatically in the outpatient consultation department. Conclusions The results of our study revealed the effects of the COVID-19 pandemic in the clinical practice of neurology in Wenzhou during the outbreak. Understanding the pandemic’s trends and impact on neurological patients and health systems will allow for better preparation of neurologists in the future.

Despite known benefits, the timing of and method used for umbilical cord clamping (UCC) in neonates remain controversial in China, as well as internationally. The objective of this study was to assess knowledge, attitudes, and practice of UCC amongst health care providers in China, as recommended by medical professional organizations.A web-based questionnaire on cord clamping practices was administered to midwives, obstetricians, and neonatologists in 126 hospitals from 16 provinces. The provinces were selected from seven different regions of China.A total of 5,005 (60.5% of eligible respondents) health care providers returned completed questionnaires. The awareness rates for immediate cord clamping (ICC) and delayed cord clamping (DCC) were over 85%, but the implementation rate for DCC was relatively low (ICC 58.3% vs. DCC 41.6%). Most neonates were placed below the introitus (92.8%) during cord clamping and this correlated with the route of delivery. The choice of UCC was impelled by different factors. Benefits for neonates influenced the choice of ICC (50%) and promoting a larger blood volume to stabilize systemic circulation influenced the choice of DCC (92.3%). Majority (91.5%) of respondents acquiesced that it was necessary to develop national clinical guidelines for UCC.The majority of obstetricians, neonatologists, and midwives who participated in this study had a positive perception of DCC. However, this did not translate to daily practice. The practice of UCC is variable and there are no standard guidelines.· The first large-scale epidemiological investigation of umbilical cord ligation is in China.. · The survey included three commonly used umbilical cord clamping methods.. · The respondents included neonatologists..

Vascular smooth muscle cell (SMC) from arterial stenotic-occlusive diseases is featured with deficiency in mitochondrial respiration and loss of cell contractility. However, the regulatory mechanism of mitochondrial genes and mitochondrial energy metabolism in SMC remains elusive. Here, we described that DNA methyltransferase 1 (DNMT1) translocated to the mitochondria and catalyzed D-loop methylation of mitochondrial DNA in vascular SMCs in response to platelet-derived growth factor-BB (PDGF-BB). Mitochondrial-specific expression of DNMT1 repressed mitochondrial gene expression, caused functional damage, and reduced SMC contractility. Hypermethylation of mitochondrial D-loop regions were detected in the intima-media layer of mouse carotid arteries subjected to either cessation of blood flow or mechanical endothelial injury, and also in vessel specimens from patients with carotid occlusive diseases. Likewise, the ligated mouse arteries exhibited an enhanced mitochondrial binding of DNMT1, repressed mitochondrial gene expression, defects in mitochondrial respiration, and impaired contractility. The impaired contractility of a ligated vessel could be restored by ex vivo transplantation of DNMT1-deleted mitochondria. In summary, we discovered the function of DNMT1-mediated mitochondrial D-loop methylation in the regulation of mitochondrial gene transcription. Methylation of mitochondrial D-loop in vascular SMCs contributes to impaired mitochondrial function and loss of contractile phenotype in vascular occlusive disease.

Vascular endothelial cells are exposed to shear stresses with disturbed vs. laminar flow patterns, which lead to proinflammatory vs. antiinflammatory phenotypes, respectively. Effective treatment against endothelial inflammation and the consequent atherogenesis requires the identification of new therapeutic molecules and the development of drugs targeting these molecules. Using Connectivity Map, we have identified vitexin, a natural flavonoid, as a compound that evokes the gene-expression changes caused by pulsatile shear, which mimics laminar flow with a clear direction, vs. oscillatory shear (OS), which mimics disturbed flow without a clear direction. Treatment with vitexin suppressed the endothelial inflammation induced by OS or tumor necrosis factor-α. Administration of vitexin to mice subjected to carotid partial ligation blocked the disturbed flow-induced endothelial inflammation and neointimal formation. In hyperlipidemic mice, treatment with vitexin ameliorated atherosclerosis. Using SuperPred, we predicted that apurinic/apyrimidinic endonuclease1 (APEX1) may directly interact with vitexin, and we experimentally verified their physical interactions. OS induced APEX1 nuclear translocation, which was inhibited by vitexin. OS promoted the binding of acetyltransferase p300 to APEX1, leading to its acetylation and nuclear translocation. Functionally, knocking down APEX1 with siRNA reversed the OS-induced proinflammatory phenotype, suggesting that APEX1 promotes inflammation by orchestrating the NF-κB pathway. Animal experiments with the partial ligation model indicated that overexpression of APEX1 negated the action of vitexin against endothelial inflammation, and that endothelial-specific deletion of APEX1 ameliorated atherogenesis. We thus propose targeting APEX1 with vitexin as a potential therapeutic strategy to alleviate atherosclerosis.

Vascular smooth muscle cell (vSMC) is the predominant cell type in the blood vessel wall and is constantly subjected to a complex extracellular microenvironment. Mechanical forces that are conveyed by changes in stiffness/elasticity, geometry and topology of the extracellular matrix have been indicated by experimental studies to affect the phenotype and function of vSMCs. vSMCs perceive the mechanical stimuli from matrix via specialized mechanosensors, translate these stimuli into biochemical signals controlling gene expression and activation, with the consequent modulation in controlling various aspects of SMC behaviors. Changes in vSMC behaviors may further cause disruption of vascular homeostasis and then lead to vascular remodeling. A better understanding of how SMC senses and transduces mechanical forces and how the extracellular mechano-microenvironments regulate SMC phenotype and function may contribute to the development of new therapeutics for vascular diseases.

We investigated the effects of potassium-releasing bacteria on physiological and bioche-mical characteristics of以‘宁杞1号’枸杞为研究对象,采用单因素随机区组试验设计,研究不添加NaCl和菌剂(CK)、100 mmol·L

BACKGROUND Liver fibrosis is a refractory disease whose persistence can eventually induce cirrhosis or even liver cancer. Early liver fibrosis is reversible by intervention. As a member of the transforming growth factor-beta (TGF-β) superfamily, bone morphogenetic protein 7 (BMP7) has anti-liver fibrosis functions. However, little is known about BMP7 expression changes and its potential regulatory mechanism as well as the relationship between BMP7 and TGF-β during liver fibrosis. In addition, the mechanism underlying the anti-liver fibrosis function of BMP7 needs to be further explored. AIM To investigate changes in the dynamic expression of BMP7 during liver fibrosis, interactions between BMP7 and TGF-β1, and possible mechanisms underlying the anti-liver fibrosis function of BMP7. METHODS Changes in BMP7 expression during liver fibrosis and the interaction between BMP7 and TGF-β1 in mice were observed. Exogenous BMP7 was used to treat mouse primary hepatic stellate cells (HSCs) to observe its effect on activation, migration, and proliferation of HSCs and explore the possible mechanism underlying the anti-liver fibrosis function of BMP7. Mice with liver fibrosis received exogenous BMP7 intervention to observe improvement of liver fibrosis by using Masson’s trichrome staining and detecting the expression of the HSC activation indicator alpha-smooth muscle actin (α-SMA) and the collagen formation associated protein type I collagen (Col I). Changes in the dynamic expression of BMP7 during liver fibrosis in the human body were further observed. RESULTS In the process of liver fibrosis induced by carbon tetrachloride (CCl4) in mice, BMP7 protein expression first increased, followed by a decrease; there was a similar trend in the human body. This process was accompanied by a sustained increase in TGF-β1 protein expression. In vitro experiment results showed that TGF-β1 inhibited BMP7 expression in a time- and dose-dependent manner. In contrast, high doses of exogenous BMP7 inhibited TGF-β1-induced activation, migration, and proliferation of HSCs; this inhibitory effect was associated with upregulation of pSmad1/5/8 and downregulation of phosphorylation of Smad3 and p38 by BMP7. In vivo experiment results showed that exogenous BMP7 improved liver fibrosis in mice. CONCLUSION During liver fibrosis, BMP7 protein expression first increases and then decreases. This changing trend is associated with inhibition of BMP7 expression by sustained upregulation of TGF-β1 in a time- and dose-dependent manner. Exogenous BMP7 could selectively regulate TGF-β/Smad pathway-associated factors to inhibit activation, migration, and proliferation of HSCs and exert anti-liver fibrosis functions. Exogenous BMP7 has the potential to be used as an anti-liver fibrosis drug.

Anti-lipopolysaccharide factors are a group of small proteins with broad spectrum antiviral property and antibacterial activity. Herein, we obtained the genomic sequence of the Procambarus clarkii anti-lipopolysaccharide factor (PcALF) gene by using polymerase chain reaction to investigate its expression pattern in various tissues and in the immune tissues (Hepatopancreas) following exposure to pathogens. The deduced protein of PcALF was conserved; it displayed the signal peptides and putative lipo-polysaccharide binding domain, particularly the two conserved cysteine amino acid residues at both ends of the domain. The recombinant protein of PcALF was successfully expressed in Escherichia coli and rabbit anti-PcALF polyclonal antibodies were prepared. The qRT-PCR analysis showed unequal distribution of PcALF transcript in the examined tissues, however the transcript level was greatest in hepatopancreas. The challenge with peptidoglycan (PGN), lipo-polysaccharide (LPS) and Poly I:C significantly enhanced expression level of PcALF in hepatopancreas when compared with the PBS control. RNA interference of PcALF affected the mRNA expression levels of immune-related genes. Taken together, our data suggested that PcALF is an inducible protein and could play a key biological role in the innate immune defense of P. clarkii.

Macrophage-mediated inflammatory responses occur throughout all stages of atherosclerosis. DNA methylation is one of the critical epigenetic mechanisms and is associated with the development of atherosclerosis. The underlying mechanism of epigenetic regulation of macrophage inflammation (M1 activation) remains unclear. Here we aim to study the role of DNA methyltransferase 1 (DNMT1) in modulating macrophage inflammation and atherosclerosis. DNMT1 expression is up-regulated in THP-1-derived macrophages upon treatment with lipopolysaccharide (LPS) and interferon-gamma (IFN-γ). Overexpression of DNMT1 promotes the LPS- and IFN-γ-induced M1 activation whereas inhibition of DNMT1 attenuates it. Consistently, DNMT1 expression is elevated in macrophages in atherosclerotic plaques from human and mouse specimens; compared with the Dnmt1wild-type, myeloid Dnmt1 deficiency in mice in an Apolipoprotein E (ApoE) knockout background or receiving AAV-PSCK9 injection and carotid partial ligation results in ameliorated atheroma formation and suppressed plaque inflammation. The promoter regions of atheroprotective Krüppel-like factor 4 (KLF4) are hypermethylated in M1- activated macrophages. DNMT1 down-regulates the expression of KLF4, probably through catalyzing DNA methylation of the promoter regions of KLF4. Gain- and loss-of function study of KLF4 indicates that the DNMT1-mediated macrophage M1 activation is dependent on KLF4. Our data demonstrate a proatherogenic role for DNMT1 as a defining factor in macrophage inflammation both in vitro and in vivo. DNMT1 promotes macrophage M1 activation by suppressing KLF4 expression. Thus macrophage-specific DNMT1 inhibition may provide an attractive therapeutic potential to prevent or reduce atherosclerosis.

Mao Mu,1,* Shi Zuo,2,* Rong-Min Wu,3 Kai-Sheng Deng,1 Shuang Lu,1 Juan-Juan Zhu,1 Gao-Liang Zou,1 Jing Yang,1 Ming-Liang Cheng,1 Xue-Ke Zhao1 1Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China; 2Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China; 3Department of Ultrasonography, The Maternity Hospital of Guizhou, Guiyang, Guizhou, China *These authors contributed equally to this work Purpose: Liver fibrosis is a worldwide health issue. Development of effective new drugs for treatment of this disease is of great importance. This study investigated the therapeutic effects of ferulic acid on liver fibrosis invitro and invivo.Materials and methods: Human hepatic stellate cell line (HSC) LX-2 was used for invitro assays. Transforming growth factor β1 (TGF-β1) was used to induce hepatic fibrosis in LX-2 cells. Western blot was used to detect protein levels of collagen I, fibronectin, α-smooth muscle actin (SMA), p-Smad2, p-Smad3, p-p38, and p-JNK. Gene expression was measured by RT-qPCR. Fluorescence staining was used to determine localization of Smad4. CCl4-induced hepatic fibrosis in SD rats was used as an invivo model. Histological features were detected by hematoxylin and eosin staining. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hexadecenoic acid (HA), and hydroxyproline (Hyp) were measured by ELISA.Results: TGF-β1 treatment significantly increased levels of collagen I, fibronectin, α-SMA, p-Smad2, p-Smad3, and Smad4 in LX-2 cells. Ferulic acid improved TGF-β1-induced hepatic fibrosis via regulation of the TGF-β1/Smad pathway. Consistent with invitro data, CCl4 caused severe hepatic fibrosis in SD rats, as determined by ALT, AST, HA, and Hyp upregulation. Protein levels of p-Smad2 and p-Smad3 in liver tissues were significantly increased following treatment with CCl4. All CCL4-induced changes were markedly attenuated by ferulic acid treatment.Conclusion: Ferulic acid potently improved hepatic fibrosis via inhibition of the TGF-β1/Smad pathway invitro and invivo. These findings provided evidence for potential use of ferulic acid to treat or prevent liver fibrosis. Keywords: ferulic acid, TGF-β1, CCl4, hepatic fibrosis, Smad signaling pathway&nbsp

Objective This study aimed to investigate whether umbilical cord milking (UCM) prevents and controls anemia in preterm infants, as compared with immediate cord clamping (ICC). Study Design Pregnant women delivering at Results Neonates receiving UCM had significant higher levels of hemoglobin (Hb), hematocrit, and serum iron (p 0.05). Conclusion UCM is an effective intervention to help preterm infants experience less anemia with the potential to increase blood volume, as seen by higher Hb levels and more enhanced iron stores.

Background Initial neurological manifestations involved with Acoustic neuromas (ANs) are easily misdiagnosed due to nonspecific symptoms. The objective is to investigate and describe the clinical features of small ANs presenting with initial neurological manifestations, to allow earlier diagnosis and more well-timed interference for patients with this disease. Methods This was a retrospective cross-sectional study that included 22 patients. The detailed clinical information with initial symptoms of neurological manifestations caused by small ANs between January 2010 and May 2020 were retrospectively analyzed. The collected data included symptoms, signs, neuroimaging results, and pathologic diagnoses. Results There were 9 males and 13 females, and their ages ranged from 22 to 74 years. Dizziness/vertigo was the most common initial presenting symptom in 9 of the 22 patients. Headache was the second most frequent initial presenting symptom in 8 of 22. Neuro-physical examination found that the facial nerve and auditory nerve were the most involved cranial nerves, with remaining positive signs involving abnormalities of the optic nerve, trigeminal nerve and abducens nerve as well as ataxia and nystagmus. More than half of the patients underwent microsurgery and had postoperative clinical symptom improvement. The patients who chose the observation method showed no change in tumor size at follow-up. Conclusions Dizziness/vertigo and headache are the most common initial neurological symptoms of small ANs and should be considered in the differential diagnosis of patients. The results suggest that MRI is the best tool in diagnosis for small ANs. Observation and microsurgery are safe and common methods for the treatment.

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent diseases worldwide. Blueberry, combined with probiotics (BP), might be a potential candidate for NAFLD treatment, due to its anti-inflammatory and anti-apoptotic properties. Here, we investigated whether the anti-inflammatory cytokine, IL-22, was involved in the therapeutic process of BP, using cell and rat models of NAFLD. Results indicated that BP significantly reduced lipid droplets and triglyceride (TG) accumulation in NAFLD cells. However, when IL-22 was deficient, the lipid droplets and TG content were significantly increased. In vivo, the serum parameters and pathological degree of NAFLD rats were significantly improved by BP, while IL-22 silencing significantly abolished the BP effect. Immunohistochemistry, immunofluorescence, qRT-PCR, and western blotting showed that the NAFLD group expressed significantly lower levels of IL-22, JAK1, and STAT3, and higher levels of BAX, than the normal group. Furthermore, BP significantly elevated the levels of IL-22, JAK1 and STAT3, and reduced the level of BAX in NAFLD, while IL-22 silencing prevented BP from restoring the expression of JAK1, STAT3, and BAX. We conclude that IL-22 is vital for the therapeutic effect of BP, and acts via activation of JAK1/STAT3 signaling and inhibition of the apoptosis factor BAX, which makes IL-22 a promising target for therapy of NAFLD.

Understanding the underlying molecular mechanisms of liver fibrosis is important to develop effective therapy. Herein, we show that focal-adhesion-kinse (FAK) plays a key role in promoting hepatic stellate cells (HSCs) activation in vitro and liver fibrosis progression in vivo. FAK activation is associated with increased expression of α-smooth muscle actin (α-SMA) and collagen in fibrotic live tissues. Transforming growth factor beta-1 (TGF-β1) induces FAK activation in a time and dose dependent manner. FAK activation precedes the α-SMA expression in HSCs. Inhibition of FAK activation blocks the α-SMA and collagen expression, and inhibits the formation of stress fibers in TGF-β1 treated HSCs. Furthermore, inhibition of FAK activation significantly reduces HSC migration and small GTPase activation, and induces apoptotic signaling in TGF-β1 treated HSCs. Importantly, FAK inhibitor attenuates liver fibrosis in vivo and significantly reduces collagen and α-SMA expression in an animal model of liver fibrosis. These data demonstrate that FAK plays an essential role in HSC activation and liver fibrosis progression, and FAK signaling pathway could be a potential target for liver fibrosis.

// Yi-ju Cheng 1,2,* , Ran Wu 3,* , Ming-liang Cheng 4 , Juan Du 1,2 , Xi-wei Hu 1 , Lei Yu 5 , Xue-ke Zhao 4 , Yu-mei Yao 4 , Qi-zhong Long 1,2 , Li-li Zhu 4 , Juan-juan Zhu 4 , Ni-wen Huang 1 , Hua-juan Liu 4 , Ya-xin Hu 4 and Fang Wan 1 1 Department of Respiratory Medicine, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China 2 Department of Respiratory Medicine, The Affiliated Baiyun Hospital of Guizhou Medical University, Guiyang, Guizhou, China 3 Department of Dermatology, The First Affiliated Hospital of Guiyang college of Traditional Chinese Medicine, Baoshanbei Guiyang, Guizhou, China 4 Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China 5 Prenatal Diagnostic Center, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China * These authors have contributed equally to this work Correspondence to: Ming-liang Cheng, email: // Lei Yu, email: // Keywords : carboplatin; anemia; neutropenia; thrombocytopenia; FDA adverse event reporting system Received : June 14, 2016 Accepted : October 21, 2016 Published : October 27, 2016 Abstract In order to clarify the risk of hematotoxicity of carboplatin, we inspected 19901 case reports of non-small cell lung cancer patients that were submitted to the FDA Adverse Event Reporting System (FAERS) between January 2004 and December 2015. These comprised 3907 cases which were treated with carboplatin and 15994 cases which were treated with other therapies in the absence of carboplatin. By comparison, carboplatin cases were significantly more likely to report anemia (OR = 2.27, 95% CI 1.85-2.78, P = 5.04×10 -15 ), neutropenia (OR = 2.27, 95% CI 1.76-2.92, P = 2.39×10 -10 ), and thrombocytopenia (OR = 2.38, 95% CI 1.84-3.08, P = 5.60×10 -11 ). We further explored published evidences and found 205 human genes interacting with carboplatin. Functional analysis corroborated that these genes were significantly enriched in the biochemical pathway of hematopoietic cell lineage (adjusted P = 6.02×10 -11 ). This indicated that carboplatin could profoundly affect the development of blood cells. Given the early awareness of the hematologic risks, great caution should be exercised in prescribing carboplatin to non-small cell lung cancer patients. And functional enrichment analysis on carboplatin-related genes warranted subsequent research with regard to the underlying toxicological mechanisms.

Purpose Liver fibrosis is a worldwide health issue. Development of effective new drugs for treatment of this disease is of great importance. This study investigated the therapeutic effects of ferulic acid on liver fibrosis in vitro and in vivo. Materials and methods Human hepatic stellate cell line (HSC) LX-2 was used for in vitro assays. Transforming growth factor β1 (TGF-β1) was used to induce hepatic fibrosis in LX-2 cells. Western blot was used to detect protein levels of collagen I, fibronectin, α-smooth muscle actin (SMA), p-Smad2, p-Smad3, p-p38, and p-JNK. Gene expression was measured by RT-qPCR. Fluorescence staining was used to determine localization of Smad4. CCl4-induced hepatic fibrosis in SD rats was used as an in vivo model. Histological features were detected by hematoxylin and eosin staining. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hexadecenoic acid (HA), and hydroxyproline (Hyp) were measured by ELISA. Results TGF-β1 treatment significantly increased levels of collagen I, fibronectin, α-SMA, p-Smad2, p-Smad3, and Smad4 in LX-2 cells. Ferulic acid improved TGF-β1-induced hepatic fibrosis via regulation of the TGF-β1/Smad pathway. Consistent with in vitro data, CCl4 caused severe hepatic fibrosis in SD rats, as determined by ALT, AST, HA, and Hyp upregulation. Protein levels of p-Smad2 and p-Smad3 in liver tissues were significantly increased following treatment with CCl4. All CCL4-induced changes were markedly attenuated by ferulic acid treatment. Conclusion Ferulic acid potently improved hepatic fibrosis via inhibition of the TGF-β1/Smad pathway in vitro and in vivo. These findings provided evidence for potential use of ferulic acid to treat or prevent liver fibrosis.

Ethanol extract (EE) from Periplaneta americana (PA) is the main ingredient of Kangfuxin, which is a popular traditional chinese medicine (TCM) and has long been used for the clinical treatment of burns, wounds and ulcers. We compared the wound-healing activities of three extracts of PA using cutaneous wound-healing in mice as the bioactivity model. These three extracts were EE, total polysaccharide and total protein. We also tracked bioactive fractions in the EE by organic reagent extraction, column chromatography and HPLC. Seven compounds were successfully identified from the water elution fraction of the EE of PA using UPLC-MS. Among these compounds, four compounds (P2, P3, P4, P5(1)) were first reported in PA. Some of these compounds have been previously reported to have various pharmacological activities that could contribute to the high wound-healing activity of PA.

The earliest atherosclerotic lesions preferentially develop in arterial regions experienced disturbed blood flow, which induces endothelial expression of pro-atherogenic genes and the subsequent endothelial dysfunction. Our previous study has demonstrated an up-regulation of DNA methyltransferase 1 (DNMT1) and a global hypermethylation in vascular endothelium subjected to disturbed flow. Here, we determined that DNMT1-specific inhibition in arterial wall ameliorates the disturbed flow-induced atherosclerosis through, at least in part, targeting cell cycle regulator cyclin A and connective tissue growth factor (CTGF). We identified the signaling pathways mediating the flow-induction of DNMT1. Inhibition of the mammalian target of rapamycin (mTOR) suppressed the DNMT1 up-regulation both in vitro and in vivo. Together, our results demonstrate that disturbed flow influences endothelial function and induces atherosclerosis in an mTOR/DNMT1-dependent manner. The conclusions obtained from this study might facilitate further evaluation of the epigenetic regulation of endothelial function during the pathological development of atherosclerosis and offer novel prevention and therapeutic targets of this disease.

Simple sequence repeats (SSRs) and sequence-related amplified polymorphism (SRAP) were employed to assess the genetic diversity and relationship among 108 ramie cultivars, which were collected from China, Japan, Indonesia and Myanmar. A total of 183 polymorphic bands were produced by using 21 SSR and 20 SRAP primer pairs. The genetic similarity matrix was obtained by using the similarity for qualitative data (SIMQUAL) subroutine of the Numerical Taxonomy and Multivariate Analysis System (NTSYS-pc) software statistical package, based on Jaccard's algorithms. The results showed that the similarity coefficient among the 108 ramie germplasms ranged from 0.22 to 0.89. By using principal components analysis (PCA) and unweighted pair-group method with arithmetic means (UPGMA), the 108 ramie germplasms were clustered into two categories. Shanon diversity index (SDI) was 1.1 and Nei's gene diversity index (NGDI) was 0.58 in the present study. When comparing their indexes, the genetic diversity in the different pro...

Electronic image stabilization (EIS) is the technology which detects and removes camera jitter in image sequences by digital image processing methods. It has been widely used in moving vehicles such as airborne, shipboard and vehicle-mounted camera systems. This paper firstly introduces the basic principle and structure of EIS system. Then the key techniques for each module are introduced and compared in processing speed and application scenes. The motion estimation method based on feature points is emphatically analyzed. Some experimental simulations and further discussion are made on the existing motion filtering and compensation methods. We also summarize the evaluation criteria for EIS performance. Finally the future research trend of EIS system is presented.

To explore the mechanism of interlukin-22 (IL-22)-mediated phosphor-Janus kinase-1(p-JAK1)/phosphor-signal transducer and activator of transcription 3 (p-STAT3) signaling way in the experiment of improving non-alcholic fatty liver disease (NAFLD) by blueberry probiotic serum.The rat serums with low-, medium-, and high-dose of 10% blueberry probiotics, as well as saline were prepared. NAFLD model was built by inducing normal liver cell line L-02 with free fatty acid (FFA).NAFLD model cells were cultured with saline serum (model group), low-, medium-, and high-dose blueberry probiotics serums (low-, medium-, and high-dose serum groups) , respectively .Normal liver cell group (normal group) was cultured with saline serum . Oil Red O staining was used to detect the lipid deposition in the cells; the intracellular level of triglyceride (TG) was quantitatively determined; the gene and protein expressions ofTwenty-four hours after modeling, a large amount of lipid deposition could be observed in model group. Compared with normal group, model group showed lower gene and protein expression levels ofThe blueberry probiotics could antagonize the NAFLD via p-JAK1/p-STAT3 signaling way.

To provide a theoretical and practical foundation for ramie genetic analysis, simple sequence repeats (SSRs) were identified in the ramie genome and employed in this study. From the 115 369 sequences of a specific-locus amplified fragment library, a type of reduced representation library obtained by high-throughput sequencing, we identified 4774 sequences containing 5064 SSR motifs. SSRs of ramie included repeat motifs with lengths of 1 to 6 nucleotides, and the abundance of each motif type varied greatly. We found that mononucleotide, dinucleotide, and trinucleotide repeat motifs were the most prevalent (95.91%). A total of 98 distinct motif types were detected in the genomic-SSRs of ramie. Of them, The A/T mononucleotide motif was the most abundant, accounting for 41.45% of motifs, followed by AT/TA, accounting for 20.30%. The number of alleles per locus in 31 polymorphic microsatellite loci ranged from 2 to 7, and observed and expected heterozygosities ranged from 0.04 to 1.00 and 0.04 to 0.83, respectively. Furthermore, molecular identity cards (IDs) of the germplasms were constructed employing the ID Analysis 3.0 software. In the current study, the 26 germplasms of ramie can be distinguished by a combination of five SSR primers including Ibg5-5, Ibg3-210, Ibg1-11, Ibg6-468, and Ibg6-481. The allele polymorphisms produced by all SSR primers were used to analyze genetic relationships among the germplasms. The similarity coefficients ranged from 0.41 to 0.88. We found that these 26 germplasms were clustered into five categories using UPGMA, with poor correlation between germplasm and geographical distribution. Our study is the first large-scale SSR identification from ramie genomic sequences. We have further studied the SSR distribution pattern in the ramie genome, and proposed that it is possible to develop SSR loci from genomic data for population genetics studies, linkage mapping, quantitative trait locus mapping, cultivar fingerprinting, and as genetic diversity studies.

Relative leaf chlorophyll (Chl.) content, leaf gas exchange, Chl. fluorescence, plant biological biomass, and fruit yield were evaluated in growing hot pepper ( Capsicum annuum L.) during the fruit-growing stages in hot summer under three shade levels (un-shade, 30% shade, and 70% shade) and four soil water contents (SWC) of 40–55%, 55–70%, 70–85%, and 85–100% of field moisture capacity (FMC). Hot pepper crops were more affected by light irradiance than by soil moisture and by their interaction during the whole observed periods. Hot pepper attained greatest relative leaf Chl. content (expressed as SPAD value) and photosynthetic activity when cultivated with 30% shade, resulting in the highest plant biological biomass and fruit yield. Although 70% shade improved leaf photosynthetic efficiency (expressed as F v /F m or F v '/F m '), crops obtained the lowest photosynthetic rate, photochemical quenching coefficient (qP), and non-photochemical quenching coefficient (NPQ). This showed that light irradiance was insufficiency in S70% (70% shade) treatment. The leaf net photosynthetic rates ( P N ), F v /F m , and fruit yield increased gradually as SWC levels increased from 40–55% to 70–85% FMC, but decreased as SWC was higher than 70–85% FMC. The water consumption increased progressively with SWC levels, but water-use efficiency (WUE) was the highest when soil moisture was 55–70% FMC. Interaction of shade and soil moisture had significant effects on P N and F v /F m , but not on other parameters. Under drought stress (40–55% and 55–70% FMC), 30% shade could relieve the droughty damage of crops and improve photosynthetic capacity and WUE, but 70% shade could not, oppositely, aggravate the damage. The positive correlation ( r 2 =0.72) between leaf P N and fruit yield was existent. This indicated that improvement of leaf photosynthesis would increase potentially marketable yield in hot pepper crops during the full fruit-growing stages. For agricultural purposes, approximately S30% (30% shade) with 70–85% FMC is suggested to cultivate hot pepper during the fruit growth stage in hot summer months.

In southern China, glucose-6-phosphate dehydrogenase (G6PD) deficiency is a significant health problem, and the incidence ranged from 0.5 to 4.08% in different Chinese population. The aims of this study are to investigate the molecular epidemiological characteristic of the G6PD gene among Chinese Hakka in southern Jiangxi province. 2331 unrelated subjects were screened for G6PD deficiency by a fluorescent test. DNA from deficient individuals was analyzed by a gene chip analysis for thirteen common Chinese G6PD mutations. In total, 3.60% (82/2331; 95% CI 2.77-4.27) of the sample were found to be G6PD-deficient. Eight mutations were found from 80 samples. However, mutation(s) for the two remaining samples were unknown. The most common mutations were G6PD Canton (1376 G>T) and G6PD Kaiping (1388 G>A), and the following mutations were 1311 polymorphism (1311 C>T), G6PD Gaohe (95 A>G), G6PD Chinese-5 (1024 C>T), G6PD Maewo (1360 C>T), Shunde (592 C>T), G6PD Viangchan (871 G>A) and Chinese-3 (493 A>G). This is the first report of G6PD deficiency among Chinese Hakka population in Jiangxi province.

Mulch is considered a desirable management technology for conserving soil moisture, improving soil temperature and soil quality. This study aimed to investigate soil conditions and hot pepper (Capsicum annuum L) performance in terms of leaf photosynthetic capacity, fruit yield and quality, and irrigation water use efficiency (IWUE) under such practices in greenhouse condition. A field experiment across 3 years was carried out with four types of mulch (without mulch [CK], wheat straw mulch [SM], plastic film mulch [FM], and combined mulch with plastic film and wheat straw [CM]). Mulch could improve soil physical properties regardless of mulch materials. FM and CM treatments improved soil moistures status and soil temperature in comparison to CK control, while SM increased soil water content and decreased soil temperature. Mulch increased leaf net photosynthesis rate (P(N)), stomatal conductance to water vapor (gs), intercellular CO(2) concentration (Ci), and transpiration rate (E), but declined instant water use efficiency (WUEi). No significant effect of mulch application on chlorophyll fluorescence was existent for the entire growth season. Fruit yield and irrigation water use efficiency (IWUE) showed some increment under all the mulch conditions. Compared to CK, the yield was enhanced by 82.3%, 65.0%, and 111.5% in 2008; 38.1%, 17.4%, and 46.5% in 2009; and 14.3%, 6.5%, and 19.6% in 2010 under SM, FM, and CM conditions, respectively. Although FM produced better fruit quality than other treatments, CM is the recommended practice for hot pepper cultivation in greenhouse condition due to working well to facilitate soil condition (moisture and temperature), plant growth, and marketable yield. (C) 2011 Elsevier B.V. All rights reserved.

There are more than 2000 ramie germplasms in the National Ramie Germplasm Nursery affiliated with the Institute of Bast Fiber Crops, Chinese Academy of Agricultural Science, China. As it is difficult to perform effective conservation, management, evaluation, and utilization of redundant genetic resources, it is necessary to construct a core collection by using molecular markers. In this study, a core collection of ramie consisting of 22 germplasms was constructed from 108 accessions by heuristic search based on 21 Simple Sequence Repeat (SSR) marker combinations. The results showed that there is a poor relationship between the core collection and the geographic distribution. The number of amplification bands for the core collection was the same as that for the entire collection. Shannon's index for three of the SSR primers (14%) and Nei's index for nine of the SSR primers (19%) were lower in the core collection than in the entire collection. The true core collection had wider genetic diversity compared with the random core collection. Collectively, the core collection constructed in this study is reliable and represents the genetic diversity of all the 108 accessions.

A novel image stabilization system is presented, which consists of a global feature point tracking based motion estimation, a Kalman filtering based motion smoothing and an image mosaic based panoramic compensation. The global motion is estimated using feature point matching and iteration with the least-square method. Then, the Kalman filter is applied to smooth the original motion vectors to effectively alleviate unwanted camera vibrations and follow the intentional camera scan. Lastly, the loss information of image boundary due to the motion compensation is reconstructed with image mosaic to improve the visual quality. The experimental results show that this system can smooth unwanted translation or rotation of the video sequences and realize a panoramic stabilization at real-time speed.

In order to determine the prevalence and molecular characterization of hemoglobinopathies in the Wuxi region of Jiangsu Province in the People's Republic of China (PRC), a total of 10,297 healthy people selected from a regional hospital were screened. Hemoglobin (Hb) electrophoresis, complete blood cell (CBC) count, polymerase chain reaction (PCR), DNA sequencing, reverse dot-blot and multiplex ligation-dependent probe amplification (MLPA) were used to detect Hb variants, thalassemias and hereditary persistence of fetal Hb (HPFH). Two thousand and twenty-one adult subjects were screened for thalassemia, five cases were identified as α-thalassemia (α-thal) carriers including three cases of the -α(3.7) (rightward) deletion, one case of the - -(SEA) deletion and one case of β-thal [IVS-II-654 (CT), (HBB: c.316-197CT)]. The incidence of Hb variants, thalassemia and HPFH/δβ-thal were 0.136% (14/10,297), 0.25% (5/2021) and 0.0001% (1/10,297), respectively. Eight genotypes of Hb variants were found, including Hb E [β26(B8)Glu→Lys, GAGAAG; HBB: c.79GA], Hb J-Bangkok [β56(D7)Gly→Asp (GGCGAC); HBB; c.170GA], Hb G-Coushatta [β22(4)Glu→Ala (GAAGCA); HBB: c.68AC], Hb Queens [α34(B15)Leu→Arg (CTGCGG) (α2 or α1); HBA2: c.104TG (or HBA1)], Hb I [α16(A14)Lys→Glu, AAGGAG (α1); HBA1: c.49AG], Hb Beijing [α16(A14)Lys→Asn (AAGAAC or AAT) (α2 or α1); HBA2: c.51GC (or HBA1) or 51GT (or HBA1)], Hb Ube-2 [α68(E17)Asn→Asp (AACGAC) (α2 or α1); HBA2: c.205AG (or HBA1)] and Hb G-Taipei [β22(B4)Glu→Gly (GAAGGA); HBB: c.68AG]. A Sicilian δβ(0)-thal, identified for the first time in Asia, was also found in this survey.

Thalassemia is the commonest inherited autosomal recessive disorders of hemoglobin in southern China. We developed and evaluated a reverse dot blot (RDB) assay combined with flow-through hybridization technology platform for the rapid and simultaneous identification of 5 types of α-thalassemia and 16 types of β-thalassemia common in Chinese. Reliable genotyping of wild-type and thalassemic genomic DNA samples was achieved by means of a gene chip on which allele-specific oligonucleotide probes were immobilized on a nylon membrane. This method involved two multiplex PCR amplification systems of α-thalassemia and β-thalassemia and one time of hybridization. The whole procedure starting from blood sampling to the identification of thalassemia genotype required less than 4h. The diagnostic reliability of this reverse dot blot assay was evaluated on 427 samples (387 cases of thalassemia and 40 healthy persons) by using direct DNA sequence analysis and gap-PCR in a blind study. These samples included 377 cases of blood, 7 cases of amniotic fluid, 18 cases of chorionic villus, and 25 cases of cord blood. The RDB gene chip was in complete concordance with the reference method. The reverse dot blot assay was a simple, rapid, accurate, and cost-effective method to identify common thalassemia genotypes in the Chinese population.