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Objectives. Previous researches have demonstrated that abnormal functional connectivity (FC) is associated with the pathophysiology of bipolar disorder (BD). However, inconsistent results were obtained due to different selections of regions of interest in previous researches. This study is aimed at examining voxel-wise brain-wide functional connectivity (FC) alterations in the first-episode, drug-naive patient with BD in an unbiased way. Methods. A total of 35 patients with BD and 37 age-, sex-, and education-matched healthy controls underwent resting-state functional magnetic resonance imaging (rs-fMRI). Global-brain FC (GFC) was applied to analyze the image data. Support vector machine (SVM) was adopted to probe whether GFC abnormalities could be used to identify the patients from the controls. Results. Patients with BD exhibited increased GFC in the left inferior frontal gyrus (LIFG), pars triangularis and left precuneus (PCu)/superior occipital gyrus (SOG). The left PCu belongs to the default mode network (DMN). Furthermore, increased GFC in the LIFG, pars triangularis was positively correlated with the triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) and negatively correlated with the scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) coding test and Stroop color. Increased GFC values in the left PCu/SOG can be applied to discriminate patients from controls with preferable sensitivity (80.00%), specificity (75.68%), and accuracy (77.78%). Conclusions. This study found increased GFC in the brain regions of DMN; LIFG, pars triangularis; and LSOG, which was associated with dyslipidemia and cognitive impairment in patients with BD. Moreover, increased GFC values in the left PCu/SOG may be utilized as a potential biomarker to differentiate patients with BD from controls.

To identify risk factors and develop a simple model to predict early prognosis of acute paraquat (PQ) poisoning patients, we performed a retrospective cohort study of acute PQ poisoning patients (n = 1199). Patients (n = 913) with PQ poisoning from 2011 to 2018 were randomly divided into training (n = 609) and test (n = 304) samples. Another two independent cohorts were used as validation samples for a different time (n = 207) and site (n = 79). Risk factors were identified using a logistic model with Markov Chain Monte Carlo (MCMC) simulation and further evaluated using a latent class analysis. The prediction score was developed based on the training sample and was evaluated using the testing and validation samples. Eight factors, including age, ingestion volume, creatine kinase-MB [CK-MB], platelet [PLT], white blood cell [WBC], neutrophil counts [N], gamma-glutamyl transferase [GGT], and serum creatinine [Cr] were identified as independent risk indicators of in-hospital death events. The risk model had C statistics of 0.895 (95% CI 0.855–0.928), 0.891 (95% CI 0.848–0.932), and 0.829 (95% CI 0.455–1.000), and predictive ranges of 4.6–98.2%, 2.3–94.9%, and 0–12.5% for the test, validation_time, and validation_site samples, respectively. In the training sample, the risk model classified 18.4%, 59.9%, and 21.7% of patients into the high-, average-, and low-risk groups, with corresponding probabilities of 0.985, 0.365, and 0.03 for in-hospital death events. We developed and evaluated a simple risk model to predict the prognosis of patients with acute PQ poisoning. This risk scoring system could be helpful for identifying high-risk patients and reducing mortality due to PQ poisoning.

As a malignant disease, lung cancer has a high morbidity and mortality rate. Baicalin is derived from Radix Scutellariae and has anti-tumor effects, however, its role in lung cancer remains unknown. Here, functional assays suggested baicalin suppressed in vitro lung cancer phenotypes. We used micro (mi)RNA array analysis to explore baicalin effects on miRNA expression. We observed baicalin increased miR-340-5p expression, whereas inhibition of this expression abolished anti-tumor effects of baicalin. Furthermore, neuroepithelial cell transforming 1 (NET1) functioned as a miR-340-5p target, and acted in a baicalin-dependent manner to regulate lung cancer progression. Thus, baicalin elicited antitumor activities by affecting the miR-340-5p/NET1 axis, suggesting a new approach to lung cancer clinical management.

Fucosylated glycosaminoglycan (FG) from sea cucumbers has been reported to have anticoagulant effects via targeting intrinsic tenase. However, FG from natural source also potentially poses risks due to its FXIIa activation and platelet aggregating effects. Here, we found that the effect of FG on human platelet aggregation depended on both the sulfation pattern and chain length. FGs with higher content of Fuc2S4S and larger molecular weight (≥14 kD) had stronger activity. Both platelet aggregation and P-selectin expression induced by TaFG (an FG from Thelenota ananas) were decreased as the molecular weight reduced. Ticagrelor, aspirin and wortmannin completely blocked the secretion (ADP) but only partially blocked the aggregation induced by TaFG. Tirofiban an αIIbβ3 antagonist however potently inhibited both the secretion and aggregation, with IC50 of 6.01 ± 1.1.97 nM. Furthermore, TaFG could bind to human αIIbβ3 with high affinity, and the affinities of two FGs were paralleled with their activity in platelet aggregation or activation. These results indicated that αIIbβ3 played an important role in TaFG-induced platelet aggregation which was mediated by PI3K, and that platelet secretion was required for the amplification of aggregation.

Barley possesses a branchless, spike-shaped inflorescence where determinate spikelets attach directly to the main axis, but the developmental mechanism of spikelet identity remains largely unknown. Here we report the functional analysis of the barley gene BRANCHED AND INDETERMINATE SPIKELET 1 (BDI1), which encodes a TCP transcription factor and plays a crucial role in determining barley inflorescence architecture and spikelet development. The bdi1 mutant exhibited indeterminate spikelet meristems that continued to grow and differentiate after producing a floret meristem; some spikelet meristems at the base of the spike formed two fully developed seeds or converted to branched spikelets, producing a branched inflorescence. Map-based cloning analysis showed that this mutant has a deletion of ~600 kb on chromosome 5H containing three putative genes. Expression analysis and virus-induced gene silencing confirmed that the causative gene, BDI1, encodes a CYC/TB1-type TCP transcription factor and is highly conserved in both wild and cultivated barley. Transcriptome and regulatory network analysis demonstrated that BDI1 may integrate regulation of gene transcription cell wall modification and known trehalose-6-phosphate homeostasis to control spikelet development. Together, our findings reveal that BDI1 represents a key regulator of inflorescence architecture and meristem determinacy in cereal crop plants.

Grain size is a major determinant of grain yield in sorghum and other cereals. Over 100 quantitative trait loci (QTLs) of grain size have been identified in sorghum. However, no gene underlying any grain size QTL has been cloned. Here, we describe the fine mapping and cloning of one grain size QTL. From an F8 recombinant inbred line population derived from a cross between inbred lines 654 and LTR108, we identified 44 grain size QTLs. One QTL, qTGW1a, was detected consistently on the long arm of chromosome 1 in the span of 4 years. Using the extreme recombinants from an F2:3 fine-mapping population, qTGW1a was delimited within a ~33 kb region containing three predicted genes. One of them, SORBI_3001G341700, predicted to encode a G-protein γ subunit and homologous to GS3 in rice, is likely to be the causative gene for qTGW1a. qTGW1a appears to act as a negative regulator of grain size in sorghum. The functional allele of the putatively causative gene of qTGW1a from inbred line 654 decreased grain size, plant height, and grain yield in transgenic rice. Identification of the gene underlying qTGW1a advances our understanding of the regulatory mechanisms of grain size in sorghum and provides a target to manipulate grain size through genome editing.

Broccoli (Brassica oleracea var. italica) is one of the most important and nutritious vegetables widely cultivated in China. In the recent four decades, several improved varieties were bred and developed by Chinese breeders. However, the efforts for improvement of broccoli are hindered by limited information of genetic diversity and genetic relatedness contained within the available germplasms. This study evaluated the genetic diversity, genetic relationship, population structure, and fingerprinting of 372 accessions of broccoli representing most of the variability of broccoli in China. Millions of SNPs were identified by whole-genome sequencing of 23 representative broccoli genotypes. Through several stringent selection criteria, a total of 1,167 SNPs were selected to characterize genetic diversity and population structure. Of these markers, 1,067 SNPs were genotyped by target sequencing (GBTS), and 100 SNPs were genotyped by kompetitive allele specific PCR (KASP) assay. The average polymorphism information content (PIC) and expected heterozygosity (gene diversity) values were 0.33 and 0.42, respectively. Diversity analysis revealed the prevalence of low to moderate genetic diversity in the broccoli accessions indicating a narrow genetic base. Phylogenetic and principal component analyses revealed that the 372 accessions could be clustered into two main groups but with weak groupings. STRUCTURE analysis also suggested the presence of two subpopulations with weak genetic structure. Analysis of molecular variance (AMOVA) identified 13% variance among populations and 87% within populations revealing very low population differentiation, which could be attributed to massive gene flow and the reproductive biology of the crop. Based on high resolving power, a set of 28 KASP markers was chosen for DNA fingerprinting of the broccoli accessions for seed authentication and varietal identification. To the best of our knowledge, this is the first comprehensive study to measure diversity and population structure of a large collection of broccoli in China and also the first application of GBTS and KASP techniques in genetic characterization of broccoli. This work broadens the understanding of diversity, phylogeny, and population structure of a large collection of broccoli, which may enhance future breeding efforts to achieve higher productivity.

Objective: To investigate the prevalence of and risk factors associated with mental health symptoms in psychiatric outpatients and their family members in China during the COVID-19 pandemic.Methods: This cross-sectional, survey-based, region-stratified study collected demographic data and mental health measurements for depression, anxiety and acute stress from 269 psychiatric patients and 231 family members in the Second Xiangya Hospital in China from April 27, 2020 to May 8, 2020. Binary logistic regression analysis was performed to identify risk factors associated with mental health outcomes.Result: The results of this survey revealed that symptoms of depression, anxiety, and acute stress were highly prevalent symptoms in the psychiatric patient group. Respondents who were female, unmarried or highly educated were significantly more likely to have the above symptoms. In the family member group, more than half of them felt that the burden of nursing had increased during the epidemic. Subjects with a high degree of burden of care were significantly more likely to exhibit the above mental health symptoms, while females were significantly more likely to have acute stress.Conclusions: The results of this survey revealed a high prevalence of mental health disorder symptoms among psychiatric patients and an increased burden of nursing among their family members after the COVID-19 outbreak in China. Understanding the risk factors in those particular groups of people help improve the public health service system for mental health problems during public health events. For further study, exploration of the needs of mental health services and dynamic change tracking will be needed.

dHG-5 (Mw 5.3 kD) is a depolymerized glycosaminoglycan from sea cucumber Holothuria fuscopunctata. As a selective inhibitor of intrinsic Xase (iXase), preclinical study showed it was a promising anticoagulant candidate without obvious bleeding risk. In this work, two bioanalytical methods based on the anti-iXase and activated partial thromboplastin time (APTT) prolongation activities were established and validated to determine dHG-5 concentrations in plasma and urine samples. After single subcutaneous administration of dHG-5 at 5, 9, and 16.2 mg/kg to rats, the time to peak concentration (Tmax) was at about 1 h, and the peak concentration (Cmax) was 2.70, 6.50, and 10.11 μg/mL, respectively. The plasma elimination half-life (T1/2β) was also about 1 h and dHG-5 could be almost completely absorbed after s.c. administration. Additionally, the pharmacodynamics of dHG-5 was positively correlated with its pharmacokinetics, as determined by rat plasma APTT and anti-iXase method, respectively. dHG-5 was mainly excreted by urine as the unchanged parent drug and about 60% was excreted within 48 h. The results suggested that dHG-5 could be almost completely absorbed after subcutaneous injection and the pharmacokinetics of dHG-5 are predictable. Studying pharmacokinetics of dHG-5 could provide valuable information for future clinical studies.

To better understand the role of polyamines (PAs) and their metabolism in responses to chilling stress in tobacco plants, this study investigated changes of endogenous PA contents, PA synthetase and oxidase activities, seedling growth and membrane permeability in tobacco (Nicotiana tabacum) cvs. MSk326 (MK, chilling-sensitive variety) and Honghuadajinyuan (HD, chilling-tolerant variety) under chilling stress. Chilling stress significantly reduced the shoot and root dry weights but improved PA contents, especially of putrescine, in the two tobacco cultivars, with higher contents in the tolerant variety. Moreover, stepwise regression analysis indicated that the relative growth rate of tobacco seedlings under chilling stress was positively correlated with endogenous PA contents, putrescine and spermidine, particularly. The above results suggested that the resistance of tobacco seedlings to chilling stress was promoted mainly by putrescine and spermidine. And further study specified that the higher PA contents in the chilling-tolerant tobacco variety were related to higher PA synthetase activities [arginine decarboxylase (ADC) and ornithine decarboxylase (ODC)] and lower oxidase activities (diamine oxidase and polyamine oxidase) under chilling stress. Again, the study demonstrated that PA biosynthesis in tobacco seedlings was mainly dependent on the ODC pathway under chilling stress, through ADC and ODC inhibitor application and recovery treatments. Compared with the ADC inhibitor (d-arginine), the ODC inhibitor (2-fluoromethyl ornithine) more significantly inhibited PA contents and increased membrane permeability in tobacco seedlings under chilling stress. In summary, the research findings suggested PAs play an important role in regulating the chilling tolerance of tobacco seedlings.

Background Previous positron emission tomography studies have reported the changes of cerebral glucose metabolism in bipolar disorder. However, the findings across studies remain controversial, containing differing results. Methods A systematic literature search of the PubMed, Embase, Cochrane Library, and Web of Science databases was conducted. We conducted a voxel‐wide meta‐analysis of cerebral glucose metabolism studies, using the seed‐based mapping approach, in patients with bipolar disorder (BD). Results We identified 7 studies suitable for inclusion, which included a total of 126 individuals with BD and 160 healthy controls. The most consistent and robust findings were an increase in cerebral glucose metabolism in the right precentral gyrus and a decrease in the left superior temporal gyrus, left middle temporal gyrus, and cerebellum. Additionally, the sex distribution and illness duration had significant moderating effects on cerebral glucose metabolism alterations. Conclusions Cerebral glucose metabolism alterations in these brain regions are likely to reflect the disease‐related functional abnormalities such as emotion and cognition. These findings contribute to a better understanding of the neurobiological underpinnings of bipolar disorder. Limitations. This study was done at a study level and cannot be addressed at the patient level. Subgroup analysis of BD I and BD II is not possible due to limited literature data., The changes of cerebral glucose metabolism in bipolar disorder remains differences. Our meta‐analysis used the seed‐based mapping approach and found that cerebral glucose metabolism alterations are likely to reflect the disease‐related functional abnormalities.

The genus Citrobacter is commonly found in environmental and industrial settings, some members of which have been used for bioremediation of heavy metals owing to the absorption ability of their biofilms. Although our previous studies have found that the outer membrane protein A (OmpA) contributes to the process of Citrobacter werkmanii biofilm formation, the underlying mechanisms remain elusive. Therefore, we deleted ompA from the genome of C. werkmanii and investigated its phenotypes in comparison to the wild type strain (WT) and the complementary strain using biochemical and molecular techniques including RNA-Seq. Our results demonstrated that the deletion of ompA led to an increase in biofilm formation on both polystyrene and glass surfaces due to upregulation of some biofilm formation related genes. Meanwhile, swimming ability, which is mediated by activation of flagellar assembly genes, was increased on semi-solid plates in the ∆ompA strain when compared with WT. Additionally, inactivation of ompA also caused increased 1,2-benzisothiazolin-3-one (BIT) resistance, differential responses to Ca2+ stress, curli protein expression and cellulose production. Finally, ∆ompA caused differential expression of a total of 1470 genes when compared with WT, of which 146 were upregulated and 1324 were downregulated. These genes were classified into different Gene Ontology (GO) and KEGG pathways. In summary, ompA in C. werkmanii contributes to a variety of biological functions and may act as a target site to modulate biofilm formation. KEY POINTS: • ompA is a negative regulator for biofilm formation by C. werkmanii. • ompA inhibits swimming motility of C. werkmanii. • ompA deletion causes different expression profiles in C. werkmanii.

Objective: Studies on alterations in the regional neural activity in the brain of patients with bipolar disorder (BD) have provided conflicting results because of different medications used and study designs. A low bone mineral density (BMD) is also observed in patients with BD. This study aimed to further explore regional neural activities in unmedicated patients with BD and their association with BMD. Methods: In this study, 40 patients with BD and 42 healthy controls were scanned through resting-state functional magnetic resonance imaging (fMRI). Imaging data were analyzed with regional homogeneity (ReHo) and pattern classification. Pearson’s correlation analyses were performed to explore the correlations between abnormal ReHo and BMD. Results: A significant increase in ReHo values in the left inferior frontal gyrus (IFG)/temporal pole, left cerebellum vermis I/vermis II/parahippocampal gyrus/brainstem, and right superior temporal gyrus (STG) and a decrease in ReHo in the occipital gyrus (OG; left middle OG/superior OG/bilateral cuneus) were found in the patients with BD (p < 0.05) compared with those in the healthy controls. No significant correlation was observed between the abnormal ReHo values in any of the brain regions of the patients with BMD.Support vector machine (SVM) analyses revealed that the ReHo values in the right STG for distinguishing patients from healthy controls showed an accuracy of 91.89%, a sensitivity of 75.68%, and a specificity of 83.78%. The ReHo values in the left cerebellum vermis I/vermis II/parahippocampal gyrus/brainstem indicated an accuracy of 78.38%, a sensitivity of 75.68%, and a specificity of 81.08%. Conclusion: This study further confirms the abnormal brain activities in extensive regions, and these brain regions are primarily located in the fronto–temporal–occipital circuit and the cerebellum vermis of patients with BD. The regional neural activity in the right STG and the left cerebellum vermis I/vermis II/parahippocampal gyrus/brainstem may serve as potential imaging markers to distinguish patients with BD from healthy controls.

Background Medical comorbidities in people with mental disorders have recently gained more attention. People with bipolar disorder (BD) often have comorbid low bone mass, which is associated with increased fracture risk and related severe outcomes. However, few clinical studies on bone metabolism in BD patients are available. This study was designed to assess bone mineral density (BMD) and related influencing factors in a sample of newly diagnosed, drug-naive individuals with BD and age- and sex-matched healthy controls. Methods Sixty-one drug-naive individuals with BD (DSM-V) and 95 healthy volunteers had their lumbar spine (L1-L4) and left hip (Neck/Troch/Ward's) BMD determined by dual-energy X-ray absorptiometry. Besides, sociodemographic and clinical assessment were collected. Between-group comparisons and within subgroup analysis were performed. Results Drug-naive patients with BD had significantly lower BMD in comparison to healthy controls in multiple sites (L1, L3, Neck, Troch, Ward's, and total hip). On subgroup analysis, overweight individuals with BD had higher bone mass, while females presented reduced BMD. Binary logistic regression showed that low BMD in multiple regions was associated with BD diagnosis, body mass index (BMI), gender, and age. Conclusion Drug-naive individuals with BD have lower BMD when compared to an age- and gender-matched healthy control sample. Low BMI and female gender are factors associated with this outcome. The underlying pathological mechanisms of BD comorbid with osteoporosis should be further explored. Clinical trial registration www.chictr.org.cn, identifier ChiCTR190002137.

Aim & methods: A decision-analytic model was constructed to simulate a real-world cohort of Chinese patients visiting a Chinese regional mental health center for long-term health outcomes and direct medical costs. Results: When compared with age and gender-matched general population, the Chinese patients with schizophrenia were associated with reduced overall survival by 20.6 years (27.6 vs 48.2 years) and reduced quality-adjusted life years (QALY) by 18.4 QALY (18.4 vs 36.8 QALY), respectively, and increased lifetime direct medical costs by about three-times (US$84,324 vs 33,387 as of 31 December 2017) on average. Conclusion: The burden of schizophrenia was mainly driven by the mortality associated with relapsed schizophrenia and direct medical costs for schizophrenia in local mental health rehabilitation institutes.

Background: The aim of this study was to evaluate the effectiveness and safety of surgical treatment of intra-articular distal radius fractures (DRFs) with the assistance of three-dimensional (3D) printing technique. Methods: Patients with intra-articular DRFs in our hospital from February 2017 to November 2018 were enrolled in this study, and were randomly assigned to 2 parallel groups to receive surgical treatment with the assistance of 3D printing technique or not. For patients in the 3D printing group, the surgical procedure was simulated with 3D physical model before surgery. Volar plate and K-wire fixation were performed in all patients. Patients in the 2 groups were compared in terms of intraoperative indexes and postoperative function. Results: A total of 32 patients were included in our study. During surgery, mean operation time in the 3D model group was significantly lower than that in the routine group (P .05). Conclusion: With the assistance of 3D printing technique, the operation time, amount of intraoperative bleeding, and times of intraoperative fluoroscopy can be reduced during the surgical treatment of intra-articular DRFs with volar plating and K-wire fixation. This technique is safe and effective, and is worth spreading in other orthopedic surgeries.

Objective Late complications after endoscopic biliary sphincterotomy (EST) include stone recurrence, but no definite risk factors for recurrence have been established. This study was performed to identify the predictors of recurrence and evaluate the clinical outcomes of EST for common bile duct stones. Methods In total, 345 eligible patients who successfully underwent EST were evaluated and followed up. Statistical analysis was performed on patients with recurrence or who had undergone at least 6 months of reliable follow-up to detect the risk factors for recurrence. Results A total of 57 patients (16.52%) developed recurrence of common bile duct stones. The median length of time until recurrence was 10.25 months (range, 6–54.4 months). Univariate analyses showed that the following factors were associated with recurrence: cholecystectomy prior to EST, prior biliary tract surgery, periampullary diverticulum, diameter of the common bile duct (>15 vs. ≤15 mm), quantity of stones, complete stone removal at the first session, and lithotripsy. Multivariate analysis identified two independent risk factors for recurrence: previous biliary tract surgery and lithotripsy. Conclusions EST for common bile duct stones is safe as indicated by patients’ long-term outcomes. Patients with a history of biliary surgery or lithotripsy are more prone to recurrence.

Oxidative damage has been implicated to be one of main mechanisms by which fluoride (F) induces toxic effects. Previous studies reported that F destroyed the epididymal structure of mouse and rabbit. Epididymis is the important place for sperm maturation. However, little is known about the effect of F on the oxidative stress status of epididymis. Therefore, the aim of the present study was to explore the changes in the activities and transcriptional levels of CuZn superoxide dismutase (CuZn-SOD, SOD1) and catalase (CAT), as well as the ultrastructure, in testis and epididymis of mice administrated with F. Sixty health Kunming mice were randomly divided into four groups. With one group untreated as controls, the others were treated with 25, 50, and 100 mg NaF/L in drinking water. After 10 weeks administration, mitochondrial ultrastructural changes in testis and epididymis were observed, including the incomplete membrane and the dissolved or disappeared cristae. Compared to the control group, the activities of both SOD1 and CAT in testis and epididymis were significantly reduced by 50 or 100 mg NaF exposure. In addition, the mRNA expressions of testicular SOD1 and CAT were also decreased significantly in 100 mg NaF/L group, while the SOD1 and CAT mRNA expressions in epididymides were significantly reduced in all F treatment groups. The above results suggest that in the presence of F, similar to testis, epididymis also loses the balance between oxidative stress and antioxidative defense, and perhaps more sensitive to F.

It is well known that high fluoride results in low fertility. Epididymis is the important place for spermatozoa maturation, which is essential for successful fertilization. In the previous studies, fluoride was reported to damage the epididymal structure of mouse and rabbit. However, the mechanism underlying sodium fluoride (NaF)-induced epididymal toxicity has not yet been well elucidated. The aim of this study is to explore the global protein alterations in epididymis of mice exposed to NaF using the iTRAQ technique. Results showed that 211 proteins were differentially expressed in both 25 and 100 mg/L NaF groups. Some of them have been proved to be important for reproduction, such as low-density lipoprotein receptor-related protein 2 (Lrp2), cytochrome c, testis-specific (Cyct), sorbitol dehydrogenase (Sord), glutathione S-transferases (GSTs), acrosin, beta-defensin 126, cysteine-rich secretory protein (Crisp) 1, and Crisp2. Gene ontology (GO) analysis suggested cellular process, organelle and catalytic activity account for high percent and number of differentially expressed proteins. 171 pathways were found after the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, among which the representative maps, such as ribosome, focal adhesion, and phagosome, were involved. Different functional categories post-translational modification, protein turnover, chaperones; translation, ribosomal structure and biogenesis; cytoskeleton; energy production and conversion are implicated in the Cluster of Orthologous Groups (COG) of proteins analysis. Subsequently, the effect of NaF on the antioxidant activity in epididymis, especially glutathione and glutathione-related enzymes, was evaluated. Results exhibited high fluoride caused low total antioxidant capacity (T-AOC), high methane dicarboxylic aldehyde (MDA), decreased reduced glutathione (GSH), and the glutathione-related enzymes [GSH peroxidase (GPx), GSH reductase (GR), and GSH S-transferase (GST)] changes in activity, protein, and mRNA expressions. In summary, NaF decreased the antioxidant activity of epididymis, especially glutathione and glutathione-related enzymes, as well as iTRAQ results, providing new explanations for the low sperm quality induced by fluoride.

Obesity is a global public health concern and may lead to a variety of complications. Previous studies have indicated that adipokines and energy‑source materials contribute to obesity and obesity‑associated insulin resistance. MicroRNAs (miRs) are endogenous 20‑ to 25‑nucleotide non‑coding RNAs associated with fat metabolism. It has been indicated that miR‑21 is associated with adipogenesis and metabolic syndrome. In the present study, the expression of miR‑21 in human mature adipocytes was analyzed using reverse transcription quantitative‑polymerase chain reaction following treatment with adipokines, including tumor necrosis factor (TNF)‑α, interleukin (IL)‑6, leptin, resistin and energy source materials, including free fatty acids (FFAs) and glucose. The current study demonstrated that the expression of miR‑21 in human mature adipocytes was upregulated following treatment with TNF‑α, IL‑6, leptin, resistin and FFAs. However, low‑ and high‑glucose did not have an effect on miR‑21 expression. These results confirmed that TNF‑α, IL‑6, leptin, resistin and FFAs may contribute to obesity and obesity‑associated insulin resistance via upregulating miR‑21 in human mature adipocytes. Therefore, miR‑21 may be a key regulatory factor of obesity and obesity‑associated insulin resistance, and represents a potential therapeutic target for the treatment of these disorders.

Background: As a bioactive composite extracted from American cockroach, Xinmailong injection (XML) is used for the treatment of congestive heart failure (CHF) in China. Clinical data has provided evidence that XML has positive inotropic properties. The objective of this study was to assess the mechanisms involved in the therapeutical effect of XML on CHF.Materials and Methods: The effects of XML on the cardiac function in isolated rat heart were measured. A Ca2+ imaging technology was used in rat cardiomyocytes (H9c2 cells) to reveal the role of XML on Ca2+ channels. Meanwhile, the effects of XML on the activities of Na+/K+ ATPase and sodium/calcium exchanger were measured. In addition, the level of reactive oxygen species and the protein expressions for the superoxide dismutase and hemeoxygenase were determined in the cardiomyocytes.Results: The results showed that XML increased the electrical impulse-induced [Ca2+]i in H9c2 cells, which was dependant on extracellular Ca2+ and was abolished by ML218-HCl (a T-type Ca2+channels antagonist) but not nimodipine (a L-type Ca2+channels antagonist). Ouabain, a Na+/K+-ATPase inhibitor, increased the electrical impulse-induced [Ca2+]i, which was significantly inhibited by XML. Moreover, XML markedly inhibited the Na+/K+ ATPase activity in H9c2 cells. In addition, XML notably reduced the production of reactive oxygen species and enhanced the protein expressions of antioxidant enzymes including superoxide dismutase 1, superoxide dismutase 2 and hemeoxygenase 1 in H9c2 cell.Conclusion: Our findings pave the ways to the better understandings of the therapeutic effects of XML on cardiovascular system.Keywords: Xinmailong Injection, American cockroach, Congestive heart failure, Calcium Channels, T-Type， Na+/K+-ATPase, Reactive oxygen species

To study variations in cochlear size and shape with potential implications for cochlear implants.A comprehension of the cochlear morphology is essential for nontraumatic electrode insertion and hearing preservation in individual surgery.A total of 310 normal developed cochleae with three-dimensional multiplanar reconstructed computed tomography images were studied. We measured the linear length of the half (1/2TL) and three quarters (3/4TL) of the basal turn, the first turn (1TL), the first two turns (2TL), and the cochlear length. The length and width of the cochlear base as well as the tilt angle within the first turn (α) and the angle between the first and second turns (γ) of the cochlea were also measured.The measurement results showed that cochlear size and shape vary greatly among individuals. The length and width of cochlear base had positive correlations with 1/2TL (r = 0.526 and r = 0.625), 3/4TL (r = 0.633 and r = 0.729), 1TL (r = 0.658 and r = 0.754), 2TL (r = 0.677 and r = 0.795) and cochlear length (r = 0.622 and r = 0.769) respectively. The mean tilt angle α was 9.72 ± 1.85 degrees while the angle γ was 14.90 ± 1.36 degrees, and both had significant positive correlations with the ratio of length to width of cochlear base (p = 0.040 and p = 0.013).The significant variations of the cochlear anatomy suggest that personalized cochlear implant is needed. The width of cochlear base has a stronger association with the linear length of cochlea. And the angle within the first turn and between the first and second turns can be predicted by the ratio of length to width of cochlear base.

From the 1940s to 1990s, heparin and warfarin have been the main anticoagulants for the prevention and treatment of thrombotic events. Since then, LMWHs and fondaparinux proved effective in clinical trials, with better pharmacokinetic profiles and no monitoring requirements. Developed in the early 21st century, DOACs have comparable efficacy to LMWHs, but increase bleeding risk, as the anticoagulant targets (FIIa, FXa) are also essential for physiological hemostasis. In contrast, selective inhibition of the intrinsic coagulation pathway may be a promising strategy for safer antithrombotic treatment. FXII, FXI and FIX inhibitors have produced favorable results in preclinical studies. Notably, intrinsic F.Xase is another promising candidate target, yet to be systematically evaluated. Here, we review the development of anticoagulants, including recent research on intrinsic F.Xase inhibitors, and the revision of coagulation models over time. Studies support optimism for future diversification of anticoagulants, which could offer more reliable and patient-specific therapy.

This study explores the efficacy and mechanism by which octreotide (OCT) alleviates paraquat (PQ)-induced pancreatic injury. Twenty-four adult male rats were randomly divided into three groups: the normal control (NC), PQ poisoning, and OCT treatment groups. The PQ-induced pancreatic injury rat model was established by administering PQ (120 mg/kg). Treatment group rats received OCT (8 μg/kg body weight) every 8 h by subcutaneous injection, 1 h after PQ administration. Rats were euthanized 24 h after PQ injection. Serum amylase, lipase, tumor necrosis factor-α, and interleukin-6 levels were markedly increased in the PQ group versus the NC group. In pancreatic tissue, PQ poisoning drastically induced necrosis and increased inflammatory cytokine and oxidative stress marker levels. Compared with the PQ group, OCT reduced pancreatic damage and histological scores, serum amylase, lipase, and inflammatory cytokine levels, as well as oxidative stress. OCT demonstrates protective effects against PQ-induced pancreatic damage through anti-inflammatory and antioxidant actions.

Quercetin, a flavonoid, has been reported to ameliorate cardiovascular diseases, such as cardiac hypertrophy. However, the mechanism is not completely understood. In this study, a mechanism related to proteasome-glycogen synthesis kinase 3 (GSK-3) was elucidated in rats and primary neonatal cardiomyocytes. Rats were subjected to sham or constriction of abdominal aorta surgery groups and treated with or without quercetin for 8 weeks. Angiotensin II (Ang II)-induced primary cardiomyocytes were cultured with quercetin treatment or not for 48 h. Echocardiography, real-time RT-PCR, histology, immunofluorescence, and Western blotting were conducted. Proteasome activities were also detected using a fluorescent peptide substrate. Echocardiography showed that quercetin prevented constriction of abdominal aorta-induced cardiac hypertrophy and improved the cardiac diastolic function. In addition, quercetin also significantly reduced the Ang II-induced hypertrophic surface area and atrial natriuretic factor (ANF) mRNA level in primary cardiomyocytes. Proteasome activities were obviously inhibited in the quercetin-treated group both in vivo and in vitro. Quercetin also decreased the levels of proteasome subunit beta type (PSMB) 1, PSMB2, and PSMB5 of the 20S proteasome as well as the levels of proteasome regulatory particle (Rpt) 1 and Rpt4 of the 19S proteasome. In particular, the PSMB5 level in the nucleus was reduced after quercetin treatment. Furthermore, phosphorylated GSK-3α/β (inactivation of GSK-3) was decreased, which means that GSK-3 activity was increased. The phosphorylation levels of upstream AKT (PKB (protein kinase B)) and liver kinase B1/AMP activated protein kinase (LKB1/AMPKα) and those of downstream extracellular signal-regulated kinase (ERK), histone H3, β-catenin, and GATA binding protein 4 (GATA4) were reduced after quercetin treatment, while hypertrophy was reversed after treatment with the GSK-3 inhibitor. In summary, quercetin prevents cardiac hypertrophy, which is related to proteasome inhibition and activation of GSK-3α/β. Upstream (AKT, LKB1/AMPKα) and downstream hypertrophic factors, such as ERK, histone H3, β-catenin, and GATA4, may also be involved.

Previous studies framed a possible link of retinoic acid (RA) regulation in brain to autism spectrum disorders (ASD) etiology. The aim of this study was to measure serum levels of RA in relation to the degree of the severity of autism. Serum RA levels were measured by enzyme-linked immunosorbent assay (ELISA) colorimetric detection Kit in 81 children with autism and 81 age-sex matched typical development children. The severity of autistic symptomatology was measured by the Childhood Autism Rating Scale (CARS) score using the Chinese version. The serum levels of RA in the children with ASD (1.68 ± 0.52 ng/ml) were significantly lower than those of control subjects (2.13 ± 0.71 ng/ml) (P 0.001). At admission, 57 children (70.4%) had a severe autism. In those children, the mean serum RA levels were lower than in those children with mild to moderate autism (1.57 ± 0.47 ng/ml VS. 1.95 ± 0.55 ng/ml; P = 0.003). Furthermore, in multivariate model, low RA level was associated with having/the presence of ASD (adjusted odd ratio[OR] 0.516; P = 0.003) and severe ASD (OR 0.415; P = 0.015) after adjusted for confounding factors. The data suggested that serum RA levels were reduced in the group with ASD, and the levels negative correlated significantly with the severity of autism.

Polyphenol oxidase (PPO) is believed to play a role in plant growth, reproduction, and resistance to pathogens and pests. PPO causes browning of grains in cereals. In this study, genetic mapping of sorghum grain for phenol color reaction (PHR) was performed using a recombinant inbred line population. Only one locus was detected between SSR markers SM06072 and Xtxp176 on chromosome 6. Two linked orthologous genes (Sb06PPO1 and Sb06PPO2) within the mapped region were discovered and cloned. Transformation experiments using Nipponbare (a PHR negative rice cultivar) showed that Sb06PPO1 from LTR108 and two Sb06PPO2 alleles from both varieties could complement Nipponbare, whereas Sb06PPO1 from 654 could not. Subsequent quantitative real-time PCR (qPCR) experiments showed that Sb06PPO1 and Sb06PPO2 functioned diversely, Sb06PPO1 was mainly expressed in young panicles before flowering. Sb06PPO2 was strongly expressed in flowering panicles, especially in hulls and branches at filling stage. Moreover, the expression of Sb06PPO1 was found to be significantly up-regulated by exogenous ABA and salt, whereas Sb06PPO2 was not changed significantly, further demonstrating functional differentiation between the two genes.

Objectives The evolution of infectious diseases (IDs) poses a challenge to many ID physicians, who must either adapt or transition to another career track. This national cross-sectional study assessed the current working conditions and problems faced by ID professionals in China. Methods A national questionnaire survey of ID physicians and their facilities throughout China was performed in May–June 2016 using stratified random sampling. Results A total of 156/300 (52.0%) ID departments and 1071/2250 (47.6%) physicians from 21 provinces participated in the survey. Overall, 151 (96.2%) of 156 hospitals had ID wards and 141 (90.4%) provided outpatient consultations. The average number of ID physicians per department was 10.32 ± 6.57. The ratio of patient beds to doctors was 5: 1, and the ratio of patient beds to nurses was 5: 1.85. Training in IDs was available in 126 (80.8%), and ID research was performed in 108 (69.2%), of the 156 departments. The main service provided by ID physicians was the management of legally notifiable communicable diseases. The annual income of 942 (88.0%) of the 1071 physicians was below $15 000. Of these physicians, 870 (81.2%) felt high or very high pressure in their work, whereas only 514 (48.0%) were satisfied or very satisfied with their jobs. Conclusions The limited medical service provided by ID physicians is poorly aligned with current healthcare demands. Moreover, the heavy workloads, high stress, poor compensation and limited career prospects for ID physicians in China impede the continued development of specialists and places them in a career dilemma. ID physicians should work to develop and diversify the field and to enhance their capacities by learning new technologies and collaborating with other medical disciplines.

The present study was undertaken to investigate the hypoglycemic effect of polysaccharides (PPSC) isolated from calyx of Physalis alkekengi var. franchetii Makino in alloxan-induced diabetic mice. Seven polysaccharide fractions were obtained through a DEAE-52 column and Sephadex G-100 gel column and they were the main composes of PPSC. The PPSC treatment could prevent the loss of body weight in diabetic mice and result in a decrease of fasting blood glucose (FBG) and glycated serum protein (GSP) and an increase of fasting serum insulin in a dose-dependent manner. The histopathological examination of pancreas revealed the ability of PPSC to protect and reverse β-cells from necrosis due destruction of alloxan in diabetic mice. Furthermore, oral PPSC upregulated the expression of PI3K, Akt and GLUT4 mRNA in skeletal muscles and adipose tissues. The results suggest that PPSC possess significant anti-diabetic activity, as evaluated using alloxanised diabetic mice model. Consequently, PPSC might be a promising candidate for the development of a new anti-diabetic agent.

As a Ca2+-permeable cationic channel, canonical transient receptor potential 5 channel (TRPC5) has been known to be involved in various functions of cells. Although TRPC5 is abundantly expressed in vascular endothelium, it remains unknown whether TRPC5 plays a role in regulating endothelial senescence. In the present study, we investigated the involvement of TRPC5 in the senescence of mouse aortic endothelial cells (MAECs). Meanwhile, the regulatory role of TRPC5 in the endothelial dysfunction in aged mice was also studied. Results showed that the endothelium-dependent relaxations were significantly promoted but the endothelium-dependent contractions were markedly attenuated in aortic rings from aged mice with TRPC5 gene knocked out compared with those from aged C57BL/6J mice. Meanwhile, the nuclear telomerase activity and nitric oxide generation were notably enhanced but the reactive oxygen species production was significantly inhibited in aged mice or in hydrogen peroxide-induced senescent MAECs lacking the TRPC5 gene. In addition, by performing the senescence-associated β-galactosidase staining the oxidative stress-induced premature senescence was markedly depressed in MAECs with TRPC5 gene deficient. Expressions of endothelial nitric oxide synthase and silent information regulator protein 1 (SIRT1) were significantly up-regulated but those of P53 and P21 were markedly down-regulated both in aged mice and in hydrogen peroxide-treated MAECs in the absence of the TRPC5 gene. These results of our study uncover novel functions of TRPC5 in regulating vascular aging.

The reproductive toxicity of fluoride has become a major concern in the world. Fluoride can decrease the abilities of sperm capacitation, hyperactivation, chemotaxis, acrosome reaction and fertilization, but the studies on the responses of sperm small noncoding RNAs (sncRNAs), especially miRNAs, to fluoride exposure are lacking. miRNAs are demonstrated to influence sperm quality and male fertility by regulating gene expression at post-transcriptional levels or translational repression. The objective of this study is to analyze miRNA profiling in sperm of mice administrated with 25 and 100 mg L(-1) sodium fluoride (NaF) for 60 d using high-throughput sequencing technology. Along with reduced sperm concentration, survival, motility, and mitochondrial membrane potential, 31 differentially expressed known miRNAs were identified in fluoride groups, compared with the control group. 671 predicted target genes against the 16 altered miRNAs were mainly involved in protease inhibitor activity, apoptosis, ubiquitin mediated proteolysis, and signaling pathways of calcium, JAK-STAT, MAPK, p53, Wnt, which were proved to be directly related to sperm quality. These findings suggested that the altered sperm miRNAs could be potential biomarkers for fluoride reproductive toxicity.

Canal wall down mastoid surgery following multiple earlier surgical failures can be revised by a well-trained experienced surgeon. A dry and safe ear is obtainable in most patients, and hearing preservation is also possible.To analyze the intra-operative findings in revision surgery for canal wall down (CWD) mastoidectomy and to ascertain the prognosis.A total of 76 revision mastoidectomies with tympanoplasties performed from March 2008 to May 2014 at the First Affiliated Hospital of Zhengzhou University in China were reviewed. The pre-operative, intra-operative, and post-operative data was recorded and analyzed.The possible reason of previous surgical failures were confirmed by the operative findings, which included inadequate mastoidectomy or persistent air-cell disease (66/76 [86.8%]), recurrent or persistent cholesteatoma (44/76 [57.9%]), excessive opened cavity combined with complications (9/76 [11.8%]), and infected cavities (68/76 [89.5%]). In this study, disease control was achieved in 70 (92.1%) patients. Complications following previous surgery were modified by revision surgery. Hearing was significantly improved in the 54 cases with ossicular replacement prosthesis. After a mean follow-up of 22 months, the group of revision surgery with ossiculoplasty as a whole experienced a statistically significant hearing gain of 16.57 ± 11.96 dB (p 0.05) at air conduction pure tone average (PTA).