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Epidemiological studies inversely associate BMI with breast cancer risk in premenopausal women, but the pathophysiological linkage remains ill-defined. Despite the documented relevance of the ‘local’ environment to breast cancer progression and the well-accepted differences in transcriptome and metabolic properties of anatomically distinct fat depots, specific breast adipose contributions to the proliferative potential of non-diseased breast glandular compartment are not fully understood. To address early breast cancer causation in the context of obesity status, we compared the cellular and molecular phenotypes of breast adipose and matched breast glandular tissue from premenopausal non-obese (mean BMI = 27 kg/m2) and obese (mean BMI = 44 kg/m2) women. Breast adipose from obese women showed higher expression levels of adipogenic, pro-inflammatory, and estrogen synthetic genes than from non-obese women. Obese breast glandular tissue displayed lower proliferation and inflammatory status and higher expression of anti-proliferative/pro-senescence biomarkers TP53 and p21 than from non-obese women. Transcript levels for T-cell receptor and co-receptors CD3 and CD4 were higher in breast adipose of obese cohorts, coincident with elevated adipose interleukin 10 (IL10) and FOXP3 gene expression. In human breast epithelial cell lines MCF10A and HMEC, recombinant human IL10 reduced cell viability and CCND1 transcript levels, increased those of TP53 and p21, and promoted (MCF10A) apoptosis. Our findings suggest that breast adipose-associated IL10 may mediate paracrine interactions between non-diseased breast adipose and breast glandular compartments and highlight how breast adipose may program the local inflammatory milieu, partly by recruiting FOXP3+ T regulatory cells, to influence premenopausal breast cancer risk.

The continuous spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world has raised unprecedented challenges to the human society. Antibodies and nanobodies possessing neutralization activity represent promising drug candidates. In this study, we report the identification and characterization of a potent SARS-CoV-2 neutralizing nanobody that targets the viral spike receptor-binding domain (S-RBD). The nanobody, termed as Nb-007, engages SARS-CoV-2 S-RBD with the two-digit picomolar binding affinity and shows outstanding virus entry-inhibition activity. The complex structure of Nb-007 bound to SARS-CoV-2 S-RBD reveals an epitope that is partially overlapping with the binding site for the human receptor of angiotensin-converting enzyme 2 (ACE2). The nanobody therefore exerts neutralization by competing with ACE2 for S-RBD binding, which is further ascertained by our in-vitro biochemical analyses. Finally, we also show that Nb-007 reserves promising, though compromised, neutralization activity against the currently-circulating Delta variant and that fusion of the nanobody with Fc dramatically increases its entry-inhibition capacity. Taken together, these data have paved the way of developing Nb-007 as a drug-reserve for potential treatment of SARS-CoV-2 related diseases.

Background The prevalence of idiopathic membranous nephropathy (IMN) is increasing worldwide and the gut microbiota is recognized to play a role in its pathology. The aim of this study was to understand the involvement of the gut–kidney axis in IMN by analyzing the composition of the gut microbiota of biopsy-proven IMN patients compared with healthy controls (HC). Methods Fecal samples from 30 patients with IMN diagnosed by renal biopsy and 30 healthy co-residents (control group) were collected for analysis in the Nephrology Department of the Second Affiliated Hospital of Harbin Medical University. The microbiota composition was analyzed by a 16S rRNA microbial profiling approach. Results The results indicated that the α- and β-diversity of IMN patients differed significantly from those of the HC groups (P Faecalibacterium, Agathobacter, and Bacteroides were less abundant in the IMN group than in the HC group (LDA score > 2). Abundant bacterial functions related to lipid metabolism were observed among IMN group. Conclusion Patients with IMN appear to have an altered gut microbiome, which could provide reference for future research on the interaction mechanism between the intestinal flora and IMN.

BACKGROUND This study aims to analyze the work behaviors of patients with allergic rhinitis (AR) during the autumn pollen season, using a 2-week diary survey. METHODS In this study, we recruited patients with seasonal allergic rhinitis (SAR) who were allergic to autumn pollen using an experience sampling method. All participants completed a 2-week survey using the WeChat app during the autumn pollen season (September 16, 2018 through to September 30, 2018). Collected data included participants' general characteristics, nasal symptoms, symptoms of insomnia, mood, and unethical work behaviors. RESULTS The results showed that pollen concentration had a significant positive effect on the symptoms of rhinitis (P

BACKGROUND Artemisia annua is an important autumnal pollen allergen for seasonal allergic rhinitis (SAR) in northern China. To date, no study has investigated allergen immunotherapy with A annua. We aimed to investigate the efficacy and mechanisms underlying A annua-sublingual immunotherapy (SLIT). METHODS This was a randomized, double-blind, placebo-controlled phase III clinical trial involving 71 SAR patients, randomized to SLIT with A annua extract (n = 47) or placebo (n = 24) for 32 weeks. Total nasal symptom score (TNSS; primary clinical end point) was evaluated at baseline (peak pollen phase (PPP) in the previous year), initiation of A annua-SLIT, 1st PPP during SLIT, end of SLIT and 2nd PPP during follow-up. Blood samples and nasal secretions were collected at beginning and after SLIT for assessment of T cells and inflammatory mediators. Safety was assessed according to adverse events (AEs) reported. RESULTS Artemisia annua-SLIT significantly reduced TNSS to a greater level from baseline (from 9.45 ± 1.68 to 6.16 ± 2.27) than placebo (from 9.29 ± 2.09 to 9.05 ± 2.40) at the 1st PPP (P

The first systematic direct diversification of a complex natural product by metal-catalyzed N-H functionalization was carried out. A new series of

Protein phosphorylation is an important cellular regulatory mechanism affecting the activity, localization, conformation, and interaction of proteins. Protein phosphorylation is catalyzed by kinases, and thus kinases are the enzymes regulating cellular signaling cascades. In the model plant Arabidopsis, 940 genes encode for kinases. The substrate proteins of kinases are phosphorylated at defined sites, which consist of common patterns around the phosphorylation site, known as phosphorylation motifs. The discovery of kinase specificity with a preference of phosphorylation of certain motifs and application of such motifs in deducing signaling cascades helped to reveal underlying regulation mechanisms, and facilitated the prediction of kinase-target pairs. In this mini-review, we took advantage of retrieved data as examples to present the functions of kinase families along with their commonly found phosphorylation motifs from their substrates.

Background: Patients with Meniere's disease (MD) may present with peripheral vestibular end organ dysfunction and balance dysfunction. Objective: This study aimed to compare the results of vestibular evoked myogenic potential (VEMP) tests with those of the sensory organization test (SOT) in patients with MD to determine whether they are correlated. Material and methods: In total, 132 patients with unilateral MD were evaluated using an audiometric test, the SOT, a caloric test and VEMP tests. Results: Cervical VEMP and ocular VEMP tests were conducted in 132 patients with MD, and the response rates of the affected side were lower than those of the unaffected side. The composite score, C5ES, and C6ES of the SOT were significantly decreased in patients with no VEMP responses compared to those with VEMP responses. Conclusions and significance: MD patients with no VEMP responses are more likely to develop balance impairment than those with VEMP responses. MD patients with otolith organ impairment may therefore have balance disorders, and should exercise caution to prevent falls and subsequent injuries.

To evaluate the relationship between the positions of cytoplasmic granulation and the oocytes developmental potential in human, we detected the developmental potentials of oocytes with centrally located cytoplasmic granulation (CLCG). The patients’ age, body mass index (BMI), Infertility duration, follicle stimulation hormone (FSH) levels, average stimulate ovulation days, gonadotropin (GN) total dose, fertilization rate, cleavage rate, high quality embryo rate, embryo utilization rate and pregnancy rate were analyzed. The results showed that there were no significant difference on patients’ age, BMI, infertility duration, FSH levels, average stimulate ovulation days, GN total dose, pregnancy rate and birth rate between CLCG group and control group in patients with BMI P > 0.05). However, there was no significant difference in fertilization rate, cleavage rate, and high quality embryo rate in patients with BMI P > 0.05). The pregnancy rate was low in both groups, but 35 and 15 healthy fetuses were born in each group. We also found that the central granulated area size did not affect fertilization rate, cleavage rate, embryo utilization rate, and high quality embryo rate (P > 0.05). These results suggested CLCG might be a normal morphology of oocyte. The oocytes from patients with or without CLCG had no significant difference in their developmental potentials. The patients who transferred CLCG embryos had successful delivery. The developmental potentials of oocytes with different CLCG grades had no obvious differences.

Aim To identify the effects and mechanism of action of Polygonatum kingianum (P. kingianum) on dyslipidemia in rats using an integrated untargeted metabolomic method. Methods A rat model of dyslipidemia was induced with a high-fat diet (HFD) and rats were given P. kingianum [4 g/(kg•d)] intragastrically for 14 wk. Changes in serum and hepatic lipid parameters were evaluated. Metabolites in serum, urine and liver samples were profiled using ultra-high performance liquid chromatography/mass spectrometry followed by multivariate statistical analysis to identify potential biomarkers and metabolic pathways. Results P. kingianum significantly inhibited the HFD-induced increase in total cholesterol and triglyceride in the liver and serum. P. kingianum also significantly regulated metabolites in the analyzed samples toward normal status. Nineteen, twenty-four and thirty-eight potential biomarkers were identified in serum, urine and liver samples, respectively. These biomarkers involved biosynthesis of phenylalanine, tyrosine, tryptophan, valine, leucine and isoleucine, along with metabolism of tryptophan, tyrosine, phenylalanine, starch, sucrose, glycerophospholipid, arachidonic acid, linoleic acid, nicotinate, nicotinamide and sphingolipid. Conclusion P. kingianum alleviates HFD-induced dyslipidemia by regulating many endogenous metabolites in serum, urine and liver samples. Collectively, our findings suggest that P. kingianum may be a promising lipid regulator to treat dyslipidemia and associated diseases.

Two new premyrsinane-type diterpenes (

Five new aconitine-type C

Objective This study aimed to investigate the success rate, complications, and success-related factors of external cephalic version (ECV) of singleton breech pregnancies after 37 gestational weeks without anesthesia. Methods We studied 40 singleton breech pregnancies in women who underwent ECV without anesthesia after 37 gestational weeks from October 2018 to March 2020. On the basis of success of ECV, the women were divided into two groups of the successful group and the failed group. Various factors were analyzed to determine those that affect the success of ECV. Results Of the 40 attempts of ECV, 24 (60.0%) were successful and 16 (40.0%) failed. With regard to success-related factors, parity was significantly different between the two groups, with more multiparous women in the successful group than in the failed group. However, none of the other factors were significantly different between the groups. Fetal outcome was good in all of the cases. Ultimately, 3 cesarean sections were performed in the successful group and 16 were performed in the failed group. Conclusions ECV of breech presentation after the 37th week of pregnancy without anesthesia is an effective and relatively safe alternative, and can effectively reduce the cesarean section rate.

Background Displaced femoral neck fractures in geriatric patients are typically treated with either hemiarthroplasty or total hip arthroplasty. The choice between hemiarthroplasty and total hip arthroplasty requires a good estimate of the patient’s life expectancy, as the recent HEALTH trial suggests that the benefits of the two operations do not diverge, if at all, until the second year post-operatively. A systematic review was this performed to determine if there sufficient information in the medical literature to estimate a patient’s life expectancy beyond two years and to identify those patient variables affecting survival of that duration. Methods Pubmed, Embase, and Cochrane databases were queried for articles reporting survival data for at least two years post-operatively for at least 100 patients, age 65 or greater, treated surgically for an isolated hip fracture. A final set of 43 papers was created. The methods section of all selected papers was then reviewed to determine which variables were collected in the studies and the results section was reviewed to note whether an effect was reported for all collected variables. Results There were 43 eligible studies with 25 unique variables identified. Only age, gender, comorbidities, the presence of dementia and fracture type were collected in a majority of studies, and within that, only age and gender were reported in a majority of the results. Most (15/ 25) variables were reported in 5 or fewer of the studies. Discussion There are important deficiencies in the literature precluding the evidence-based estimation of 2 year life expectancy. Because the ostensible advantages of total hip arthroplasty are reaped only by those who survive two years or more, there is a need for additional data collection, analysis and reporting regarding survival after geriatric hip fracture.

To explore the real world clinical application characteristics and the drug combination regularity of Ciwujia Injection, 12 554 cases of patients with Ciwujia Injection were extracted from the information systems of 24 class Ⅲ grade A hospitals in China, and a standardized analysis was carried out. Most of the patients were middle-aged and old-aged, and the main departments were cardiovascular department(22.50%) and neurology department(17.92%). Before 2008, 93.77% of the patients were single overdose users, which reduced to only 2.07% after 2011. The course of treatment was mostly between 8-14 days(32.98%). The top three di-seases diagnosed by Western medicine were hypertension(11.78%), cerebral infarction(9.47%), and coronary heart disease(8.15%), and the most common traditional Chinese medicine syndrome was the deficiency of liver and kidney(18.59%). The most commonly used Western medicine was Acetylsalicylic Acid(51.07%), and the most commonly used traditional Chinese medicine was Danshen Injection(9.67%). The most commonly used Western medicine in combined application was calcium channel blocker(46.88%), and the most commonly used traditional Chinese medicine in combined application was stasis removing agent(93.21%). And the drug combination with the highest support was Isosorbide Mononitrate + Acetylsalicylic Acide, with a high recovery rate after discharge(96.81%). The results showed that Ciwujia Injection had certain regularity. It considered underlying concurrent diseases, anticoagulation and blood circulation, with a wide range of effects in strengthening the body and regulating the mind. The results could expand the understanding of Ciwujia Injection and provide a more detailed real world basis and reference for optimizing therapeutic regimen in clinic.

To explore the population characteristics and clinical application characteristics of patients with cerebral hemorrhage treated with Xingnaojing Injection in real world. The model was established by Apriori algorithm, and the general information and medication information of 8 369 patients with cerebral hemorrhage treated with Xingnaojing Injection were analyzed by using Clementine 12.0 in the databases of information systems of 33 class Ⅲ grade A hospitals in China. The results showed that among the 8 369 patients with cerebral hemorrhage treated with Xingnaojing Injection, the median age was 59 years old. And the male to female ratio was about 1.74∶1. Most of them did manual labor(31.26%), and were hospitalized in winter(27.46%), especially during the Cold Dew(5.1%). The majority of the patients were in a stable condition(50.94%), and preferred neurosurgery department(48.82%). 29.03% of patients were hospitalized for 15-28 days, and 42.47% of patients spent 10 000-50 000 Yuan of hospitalization expenses. The single dose of Xingnaojing Injection was 10-20 mL at most(46.03%). And the course of medication was mostly 3 days or less(68.60%). Lidocain was the most frequently used Western medicine in drug combination(5.05%), and Huayu Tongmai Ji was the most frequently used traditional Chinese medicine in drug combination(10.73%). The most frequently used one type of traditional Chinese medicine combined with one type of Western medicine was Huayu Tongmai Ji + Dexamethasone(8.08%). The most frequently used two Western medicines in drug combination were Omeprazole + Dexamethasone(5.07%). Prilosec + Dexamethasone + Lidocaine(3.35%) were three Western drugs with the most frequent combination. When the dosage was 10-20 mL and the number of days of treatment wasgt; 15 days, the largest number of the patients was cured and improved(44.78%, 45.85%). The results showed that cerebral hemorrhage patients treated with Xingnaojing Injection were mostly middle-aged and elderly people, with more males than females. Brain hemorrhage often occurred in winter and spring. Xingnaojing Injectiont was often combined with glucocorticoids, proton pump inhibitors and cardiovascular drugs to prevent cerebral hemorrhage complications. The clinical medication met the guidelines for the treatment of cerebral hemorrhage. Some patients had over-treatment use, which can provide a reference for clinicians in treating cerebral hemorrhage.

The ability to reliably distinguish benign from malignant solid liver lesions on ultrasonography can increase access, decrease costs, and help to better triage patients for biopsy. In this study, we used deep learning to differentiate benign from malignant focal solid liver lesions based on their ultrasound appearance.Among the 596 patients who met the inclusion criteria, there were 911 images of individual liver lesions, of which 535 were malignant and 376 were benign. Our training set contained 660 lesions augmented dynamically during training for a total of 330,000 images; our test set contained 79 images. A neural network with ResNet50 architecture was fine-tuned using pre-trained weights on ImageNet. Non-cystic liver lesions with definite diagnosis by histopathology or MRI were included. Accuracy of the final model was compared with expert interpretation. Two separate datasets were used in training and evaluation, one with all lesions and one with lesions deemed to be of uncertain diagnosis based on the Code Abdomen rating system.Our model trained on the complete set of all lesions achieved a test accuracy of 0.84 (95% CI 0.74-0.90) compared to expert 1 with a test accuracy of 0.80 (95% CI 0.70-0.87) and expert 2 with a test accuracy of 0.73 (95% CI 0.63-0.82). Our model trained on the uncertain set of lesions achieved a test accuracy of 0.79 (95% CI 0.69-0.87) compared to expert 1 with a test accuracy of 0.70 (95% CI 0.59-0.78) and expert 2 with a test accuracy of 0.66 (95% CI 0.55-0.75). On the uncertain dataset, compared to all experts averaged, the model had higher test accuracy (0.79 vs. 0.68, p = 0.025).Deep learning algorithms proposed in the current study improve differentiation of benign from malignant ultrasound-captured solid liver lesions and perform comparably to expert radiologists. Deep learning tools can potentially be used to improve the accuracy and efficiency of clinical workflows.

Caloric restriction (CR) is explored to limit the caloric intake without malnutrition. CR can affect the levels of various metabolites in organism, such as lipids, free fatty acids, ketones, bile acids and amino acids, etc, and is thought being able to extend the lifespan, postpone and reduce the incidence of age-related disorders (e.g., type 2 diabetes, cancer and cardiovascular diseases). These effects are mainly attributed to the role of CR in energy metabolism. The mechanism of CR on energy metabolism is closely related to biological clock, hormonal production, gastrointestinal flora and inflammation. Here we briefly review the effects and mechanism of CR on energy metabolism.

From 2001 to 2015, medical data of 16 856 elderly patients aged 65 years and over who used Suxiao Jiuxin Pills in the information system of 37 tertiary A-level hospitals were collected. After standardized analysis, it was found that the average age of 16 856 elderly patients was 72.48 years, and the main admission departments were department of cardiology(19.30%) and geriatric department(9.77%). Generally, 61.96% of the degree of illness is average, and the average hospitalized days were 16.16 days; 47.97% of the patients were diagnosed as coronary heart disease by Western medicine, and 5.86% of the patients were diagnosed as Qi deficiency and blood stasis; The more common combination of Western medicine was isosorbide nitrate(61.15%), Aspirin Enteric Coated Tablets(50.77%) and Gansu(36.88%), the combination of traditional Chinese medicine is Compound Danshen Dropping Pills/Tablets(19.13%), Xuesaitong Capsules/Injection(15.01%), Shexiang Baoxin Pills(12.29%); the commonly used Western medicine is vasodilator(78.39%), Chinese medicine is Huoxue Huayu(82.04%), and the commonly used Western medicine is Aaspirin Enteric Coated Tablets+Isosorbide Nitrate. The author intends to explore the valuable clinical characteristics and the clues of the combined medication scheme, and find that the application of Suxiao Jiuxin Pills basically conforms to the instructions, conforms to the characteristics of the elderly with many common diseases and complicated concurrent diseases; the combination of drugs and the indications-coronary heart disease guidelines are consistent, with certain rules to follow, and expand the recognition of the clinical application of Suxiao Jiuxin Pills, and provide clinical diagnosis and treatment ideas.

To understand and analyze the epidemic status of human intestinal parasitic diseases in the ecological region of the Qinba Mountains in Henan Province, so as to provide the evidence for the control of the diseases in this region.According to the methods ofTotally 6 706 residents were recruited in this study, 8 kinds of parasites were found including 3 species of helminthes and 5 species of protozoans. The overall infection rate of intestinal parasites was 3.39%, covering 2.92% for helminthes and 0.49% for protozoans. The infection rate ofThe infection rates of human intestinal parasites in the ecological region of the Qinba Mountains in Henan Province have decreased sharply.[

Gastric cancer is the fourth most common type of cancer and the second cause of cancer‑related mortalities worldwide despite the use of multimodal therapy. Cadherins are transmembrane glycoproteins that are involved in tumorigenesis. CDH17 has been found to be over‑expressed in gastric cancer and its overexpression was associated with lymph node metastasis and tumor‑node‑metastasis stage of the patients, yet the exact role and molecular mechanism of CDH17 in gastric cancer have not been determined. Using a lentiviral system as a delivery mediator of RNA interference, we found that inhibition of CDH17 can lead to reduce proliferation and increase apoptosis of gastric cancer cell line MKN28 in vitro and significantly diminish their tumorigenicity in vivo. Our results of the present study suggest that CDH17 may be a promising candidate for the therapeutic targeting of gastric cancer.

Adipocytokines apelin peptide, the ligand of APJ (putative receptor related to the angiotensin receptor AT1), plays key roles in the pathogenesis and deterioration of cancer. In lung cancer, apelin elevating microvessel densities has been reported. Our previous research has characterized that apelin-13 promoted lung adenocarcinoma cell proliferation. However, the effect of apelin on metastasis in lung adenocarcinoma and the underlying mechanisms remain unclear. This study shows that apelin-13 induced human adenocarcinoma cell migration via the APJ receptor. Apelin-13 phosphorylated PAK1 and cofilin increase the migration of lung adenocarcinoma cells. Moreover, the results verify that over-expression of apelin and APJ contributed to reducing the effect of doxorubicin and razoxane on inhibiting lung adenocarcinoma cells metastasis. Hypoxia activated APJ expression and apelin release in lung adenocarcinoma cells. The results demonstrate a PAK1-cofilin phosphorylation mechanism to mediate lung adenocarcinoma cells migration promoted by apelin-13. This discovery further suggests that APJ and its downstream signalling is a potential target for anti-metastatic therapies in lung adenocarcinoma patients.

To investigate the protective effect and possible mechanism of recombinant adiponectin on apoptosis in Human Umbilical Vein Endothelial Cells (HUVECs) induced by tert-butyl hydroperoxide (t-BHP).HUVECs were cultured in vitro and apoptosis was induced by t-BHP. On this basis, HUVECs were transfected with adenovirus carrying adiponectin prior to exposure to t-BHP, to further explore the protective effect of adiponectin on apoptosis induced by t-BHP. The percentage of cell viability was determined by MTT assay. The apoptotic rate was evaluated by fluorescence microsopic analysis with Hochest/PI staining. The protein levels of p-JNK, JNK and Caspase 3 were detected by Western blot.Following t-BHP 100Continuous exposure to t-BHP induced apoptosis in HUVECs. Recombinant adiponectin protected HUVECs from apoptosis induced by t-BHP, which was correlated with the downregulation of p-JNK and active Caspase 3.

To understand the epidemic status of principal human parasitosis in the ecological region of Huaiyang hills of Henan Province.According to the scheme of The 3rd National Survey of Principal Human Parasites made by National Institute of Parasitic Diseases, the survey was performed based on the ecological regions. The stratified cluster sampling was made combined with the economic and geographical conditions. The infections of intestinal helminths and protozoans in permanent residents were respectively detected by Kato-Kats technique and iodine solution.Totally 6 710 residents in 26 survey spots from 9 counties were detected, in which 528 children aged 3 to 6 years were detected forThe infection rates of principal human parasites in Huaiyang hilly ecological region of Henan have decreased sharply, but more efforts still should be paid on the prevention and control of parasitosis in children.

Genome-wide association studies (GWASs) have been performed extensively in diverse populations to identify single nucleotide polymorphisms (SNPs) associated with complex diseases or traits. However, to date, the SNPs identified fail to explain a large proportion of the variance of the traits/diseases. GWASs on type 2 diabetes (T2D) and obesity are generally focused on individual traits independently, and genetic intercommunity (common genetic contributions or the product of over correlated phenotypic world) between them are largely unknown, despite extensive data showing that these two phenotypes share both genetic and environmental risk factors. Here, we applied a recently developed genetic pleiotropic conditional false discovery rate (cFDR) approach to discover novel loci associated with BMI and T2D by incorporating the summary statistics from existing GWASs of these two traits. Conditional Q-Q and fold enrichment plots were used to visually demonstrate the strength of pleiotropic enrichment. Adopting a cFDR nominal significance level of 0.05, 287 loci were identified for BMI and 75 loci for T2D, 23 of which for both traits. By incorporating related traits into a conditional analysis framework, we observed significant pleiotropic enrichment between obesity and T2D. These findings may provide novel insights into the etiology of obesity and T2D, individually and jointly.

Background: The objective of this meta-analysis was to compare the efficacy and safety of minimally invasive plate osteosynthesis (MIPO) and conventional plate osteosynthesis (CPO) for humeral shaft fracture. Methods: Potential academic articles were identified from the Cochrane Library, Medline (1966–2016.3), PubMed (1966–2016.3), Embase (1980–2016.3), and ScienceDirect (1966–2016.3). Gray studies were identified from the references of the included literature. Randomized controlled trials (RCTs) and non-RCT involving MIPO and CPO for humeral shaft fracture were included. Two independent reviewers performed independent data abstraction. I2 statistic was used to assess heterogeneity. Fixed or random effects model was used for meta-analysis. Results: Two RCTs and 3 non-RCTs met the inclusion criteria. There was a lower incidence of iatrogenic radial nerve palsy in patients with MIPO (P = 0.006). There was no statistically significant difference in in the risk of developing nonunion, delay union, malformation, screw loosening, infection, operation time, UCLA, and MEPS function score between the 2 groups. Conclusion: MIPO decreased incidence of iatrogenic radial nerve palsy and is an efficacy and safety technique for humeral shaft fracture. Due to the limited quality and data of the evidence currently available, more high-quality RCTs are required.

Allergic rhinitis (AR) is a chronic systemic allergic disease with an association reported between allergy and anxiety. The objective of the current study was therefore to investigate and retrospectively evaluate the factors that may possibly induce state and trait anxiety among patients with AR and vasomotor rhinitis (VMR).A total of 253 outpatients suffering from AR and 108 suffering from VMR were assessed for nasal symptoms experienced during the 14 days prior to assessment. All patients scored the severity of their symptoms on a visual analogue scale (VAS) and answered the State-Trait Anxiety Inventory (STAI) questionnaire to evaluate their state (STAI-S) and trait (STAI-T) anxiety scores. Pearson's correlation and multiple regression tests were employed to assess correlations between symptom scores and anxiety status scores.The STAI-S/T scores were not significantly different between AR and VMR patients; however, for AR patients, STAI-S and STAI-T were significantly associated with nasal obstruction and the total nasal symptom scores. Multiple regression analysis further demonstrated that only nasal obstruction significantly influenced both STAI-S and STAI-T scores. In contrast, nasal itching and total nasal symptom scores were significantly correlated with the STAI-S and STAI-T scores in VMR patients, whereas continuous sneezing VAS scores were significantly associated with only the STAI-S score. However, multiple regression analysis showed that the associations between any of the 4 nasal symptom scores and STAI-S and STAI-T scores were not significant.Nasal obstruction may play a prominent role in mediation of anxiety in patients suffering from AR, but not in patients suffering from VMR.

Ajudes rebudes: Marie Curie Career Integration Grant; Dexeus Foundation for Women's Health Research; i Contratos Ramón y Cajal CD11c is an α integrin classically employed to define myeloid dendritic cells. Although there is little information about CD11c expression on human T cells, mouse models have shown an association of CD11c expression with functionally relevant T cell subsets. In the context of genital tract infection, we have previously observed increased expression of CD11c in circulating T cells from mice and women. Microarray analyses of activated effector T cells expressing CD11c derived from naïve mice demonstrated enrichment for natural killer (NK) associated genes. Here we find that murine CD11c+ T cells analyzed by flow cytometry display markers associated with non-conventional T cell subsets, including γδ T cells and invariant natural killer T (iNKT) cells. However, in women, only γδ T cells and CD8+ T cells were enriched within the CD11c fraction of blood and cervical tissue. These CD11c+ cells were highly activated and had greater interferon (IFN)-γ secretory capacity than CD11c- T cells. Furthermore, circulating CD11c+ T cells were associated with the expression of multiple adhesion molecules in women, suggesting that these cells have high tissue homing potential. These data suggest that CD11c expression distinguishes a population of circulating T cells during bacterial infection with innate capacity and mucosal homing potential.

Altres ajuts: Marie Curie Career Integration Grant i una beca Fundació Dexeus Salut de la Dona Efforts to develop vaccines that can elicit mucosal immune responses in the female genital tract against sexually transmitted infections have been hampered by an inability to measure immune responses in these tissues. The differential expression of adhesion molecules is known to confer site-dependent homing of circulating effector T cells to mucosal tissues. Specific homing molecules have been defined that can be measured in blood as surrogate markers of local immunity (e.g. α4β7 for gut). Here we analyzed the expression pattern of adhesion molecules by circulating effector T cells following mucosal infection of the female genital tract in mice and during a symptomatic episode of vaginosis in women. While CCR2, CCR5, CXCR6 and CD11c were preferentially expressed in a mouse model of Chlamydia infection, only CCR5 and CD11c were clearly expressed by effector T cells during bacterial vaginosis in women. Other homing molecules previously suggested as required for homing to the genital mucosa such as α4β1 and α4β7 were also differentially expressed in these patients. However, CD11c expression, an integrin chain rarely analyzed in the context of T cell immunity, was the most consistently elevated in all activated effector CD8+ T cell subsets analyzed. This molecule was also induced after systemic infection in mice, suggesting that CD11c is not exclusive of genital tract infection. Still, its increase in response to genital tract disorders may represent a novel surrogate marker of mucosal immunity in women, and warrants further exploration for diagnostic and therapeutic purposes.

Objective: To compare the onset of action, efficacy, and safety of azelastine and levocabastine in the treatment of allergic rhinitis. Subjects and Methods: In a multicenter, randomized, double-blind, parallel-group trial, 244 patients with moderate-to-severe allergic rhinitis were randomized to receive either azelastine hydrochloride nasal spray (ANS) 0.1% or levocabastine hydrochloride nasal spray (LNS) 0.05% for 14 consecutive days. A visual analog scale was used to record total nasal symptom score (TNSS) changes. Indexes for further assessment included onset of action, total effective rate, and evaluation of therapeutic effect. Results: Statistically significant changes from baseline in TNSS were seen in both the LNS group and the ANS group. No significant differences were seen between the two groups in terms of evaluation of therapeutic effect, total effective rate, and onset of action, except for a higher symptom relief rate in the LNS group than in the ANS group within 30 min of administering the first dose. Adverse reactions were mild to moderate, with an incidence of 0.9% for LNS and 2.5% for ANS. Conclusion: Both ANS and LNS were effective and safe in the treatment of moderate-to-severe persistent allergic rhinitis. Moreover, LNS reached a higher symptom relief rate within 30 min of administering the first dose.

The antimicrobial resistance and the character of integrons were determined in 58 Shigella flexneri strains isolated from China. All isolates were multi-drug resistant and found to carry integrons of class 1 (94.8%), class 2 (100%), or both (94.8%). No intI3 was detected. The typical class 1 integrons were found in conjugative plasmids and could be transferred to the recipient E. coli DH5α. The gene cassettes of typical class 1 integrons dfrA17-aadA5 and dfrA12-orfF-aadA2 were detected in 54 strains (93.1%) and 1 strain, respectively. Atypical class 1 integrons located on the chromosome with gene cassettes bla (oxa-30)-aadA1 were detected in 55 isolates (94.8%). All the intI2 positive isolates carried gene cassettes dfrA1-sat1-aadA1. To our knowledge, this is the first report that atypical and typical class 1 integrons coexisted with class 2 integron in multi-drug resistant S. flexneri strains.

To explore the mechanisms involved in ox-LDL transcytosis across endothelial cells and the role of caveolae in this process. An in vitro model was established to investigate the passage of oxidized low density lipoprotein (ox-LDL) through a tight monolayer of human umbilical vein endothelial cells (HUVEC) cultured on a collagen-coated filter. Passage of DiI-labeled ox-LDL through the monolayer was measured using a fluorescence spectrophotometer. The uptake and efflux of ox-LDL by HUVEC were determined using fluorescence microscopy and HPLC. Caveolae inhibitors – carrageenan (250 μg/mL), filipin (5 μg/mL), and nocodazole (33 μmol/L)–decreased the transport of ox-LDL across the monolayer by 48.9%, 72.4%, and 79.8% as compared to the control group. In addition, they effectively decreased ox-LDL uptake and inhibited the efflux of ox-LDL. Caveolin-1 and LOX-1 were up-regulated by ox-LDL in a time-dependent manner and decreased gradually after depletion of ox-LDL (P

Aims:To evaluate the efficacy and tolerability of nonpenetrating filtering surgery in the treatment of patients with open-angle glaucoma. Methods: Pertinent studies were selected by extensive searches. A total of 17 randomized controlled trials were included in the present meta-analysis. The main outcome measures were risk differences (RDs) of complete success for efficacy and postoperative complications for tolerability. Pooled estimates were computed according to a random-effects model. Results:Viscocanalostomy and deep sclerectomy were significantly less effective than tra- beculectomy, and pooled RDs of complete success were –0.16 (95% confidence interval, CI, –0.30 to –0.02) and –0.10 (–0.19 to 0.00). Deep sclerectomy plus mitomycin C (MMC) was also less effective than trabeculectomy plus MMC, with pooled RD of complete success being –0.16 (95% CI –0.32 to –0.01). Viscocanalostomy and deep sclerectomy caused main complications in fewer patients than trabeculectomy. Conclusions:Viscocanalostomy and deep sclerectomy were less effective than trabeculectomy in the treatment of open-angle glaucoma, and deep sclerectomy plus MMC was also less effective than trabeculectomy plus MMC. However, viscocanalostomy and deep sclerectomy were associated with fewer complications than trabeculectomy.

Tyroservatide (YSV) is an active, low-molecular-weight polypeptide that has been shown to have antitumor effects on human hepatocellular carcinoma BEL-7402 cells in vitro and in vivo. Multi-drug resistance (MDR) represents a major obstacle to the success of cancer chemotherapy. To enhance the chemosensitivity of tumor cells, attention has been focused on MDR modulators. In this study, we evaluated the reversal effect of YSV on MDR, and explored its mechanism of action in vitro. Administration of YSV reversed the multi-drug resistance of human hepatocellular carcinoma BEL-7402/5-FU cells significantly. The intracellular accumulation of doxorubicin and Rhodamine-123 (Rh123) were increased, which implied that the function of the P-glycoprotein (P-gp) efflux pump was inhibited by YSV. Moreover, the mRNA and protein expression of multi-drug resistance gene (MDR1) were also decreased by YSV. We observe that lung-resistance protein (LRP) and multi-drug resistance-associated protein (MRP1) each contribute to MDR in BEL-7402/5-FU cells as well. The mRNA and protein expression of LRP were decreased by YSV. No significant change was observed in mRNA expression of MRP1. However, we observe that the MRP1 protein level was reduced after treatment with YSV. These data demonstrate that YSV effectively reverses MDR in BEL-7402/5-FU cells, and that its mechanism of action is associated with the down-regulation of MDR1, MRP1 and LRP expression, as well as the inhibition of P-gp function.

Objective : Cardiac contractility is regulated tightly as an extrinsic and intrinsic homeostatic mechanism to the heart. The molecular basis of the intrinsic system is largely unknown. Here, we test the hypothesis that bone morphogenetic protein-2 ( BMP-2 ) mediates embryonic cardiac contractility upstream of myocyte-specific enhancer factor 2A ( MEF2A ). Methods : The BMP-2 and MEF2A expression pattern was analyzed by RT-PCR, Western blotting, whole-mount in situ hybridization, and an in vivo transgenic approach. The cardiac phenotype of BMP-2 and MEF2A knock-down zebrafish embryos was analysed. Cardiac contractions were recorded with a video camera. Myofibrillar organization was observed with transmission electron microscopy. Gene expression profiles were performed by quantitative real-time PCR analysis. Results : We demonstrate that BMP-2 and MEF2A are co-expressed in embryonic and neonatal cardiac myocytes. Furthermore, we provide evidence that BMP-2 is required for cardiac contractility in vitro and in vivo and that MEF2A expression can be activated by BMP-2 signaling in neonatal cardiomyocytes. BMP-2 is involved in the assembly of the cardiac contractile apparatus. Finally, we find that exogenous MEF2A is sufficient to rescue ventricular contractility defects in the absence of BMP-2 function. Conclusions : In all, these observations indicate that BMP-2 and MEF2A are key components of a pathway that controls the cardiac ventricular contractility and suggest that the BMP2-MEF2A pathway can offer new opportunities for the treatment of heart failure.

The objective of this study was to determine the effects of adenovirus-mediated vascular endothelial growth factor (Ad-VEGF) on the angiogenesis and survival of free-fat tissue transplantation in nude mice. Thirty 6-week-old CD-1 nude male mice were injected with 1ml fat tissue (harvested by suction-assisted lipectomy from the breast of humans) in the subcutaneous of scalp and were randomised into three groups of 10 animals each. Group 1 was the study group, in which Ad-VEGF was mixed with transplanted fat tissue and injected into mice. In group 2, adenovirus-mediated green fluorescent protein (Ad-GFP) gene was mixed with transplanted fat tissue and injected into the mice. In group 3, normal saline alone was used. Both group 2 and group 3 are control groups. The animals were euthanised 15 weeks after the procedure. The fat survival weight and volume of the study group were significantly greater than those of two control groups (p

Selective serotonin receptor inhibitor (SSRI) and serotonin-noradrenaline reuptake inhibitor (SNRI) users have been reported to have an increased risk of upper gastrointestinal bleeding (UGIB), but their association with lower gastrointestinal bleeding (LGIB) is less studied. This study aimed to analyze the incidence of UGIB and LGIB among SSRI users, SNRI users, and controls. Using the National Health Insurance Research Database of Taiwan, 9753 subjects who were taking serotonin reuptake inhibitors (8809 with SSRIs, and 944 with SNRIs), and 39,012 age, sex, and enrollment time-matched controls were enrolled at a 1:4 ratio. The log-rank test was used to analyze differences in the cumulative hazard of UGIB and LGIB between groups. Cox proportional hazard regression analysis was used to evaluate the independent risk factors for UGIB and LGIB. During the 10-year follow-up period from 2000 to 2010, SSRI users, but not SNRI users, had significantly higher incidences of UGIB and LGIB than the controls (P

To investigate the psychological statuses of Chinese adults with moderate-to-severe persistent allergic rhinitis, and evaluate the effects of nasal symptoms on their psychological statuseses.The Symptom Checklist-90 (SCL-90) or self-reporting Inventory was employed to analyze the psychological statuses of 539 adults with moderate-to-severe persistent allergic rhinitis.The SCL-90 scores of the adults with moderate-to-severe persistent allergic rhinitis were statistically higher than those of non-allergic adults in terms of somatization, depression, anxiety and hostility. No statistical discrepancies existed in gender or age. The course of disease contributed to somatization and compulsion. The effects of nasal symptoms included two aspects: nasal obstruction had a conspicuous impact on somatization, compulsion, interpersonal sensitivity, depression, anxiety and psychosis, while nasal itching contributed to somatization, depression and anxiety.The psychological statuses of adults with moderate-to-severe persistent allergic rhinitis is evidently worse than that of non-allergic adults. Symptoms such as nasal obstruction and itching had an obvious impact on outpatients' psychological statuses.

The effectiveness and stability of epithelial barrier depend on apical junctional complexes, which consist of tight junctions (TJs) and adherens junctions (AJs). E-cadherin is the primary component of AJs, and it is essential for maintenance of cell-to-cell interactions and regulates the epithelial barrier. However, the exact mechanism underlying E-cadherin expression, particularly at the posttranscriptional level, remains largely unknown. RNA-binding proteins CUG-binding protein 1 (CUGBP1) and HU antigen R (HuR) are highly expressed in the intestinal epithelial tissues and modulate the stability and translation of target mRNAs. Here, we present evidence that CUGBP1 and HuR interact directly with the 3′-untranslated region of E-cadherin mRNA and regulate E-cadherin translation. CUGBP1 overexpression in Caco-2 cells inhibited E-cadherin translation by increasing the recruitment of E-cadherin mRNA to processing bodies (PBs), thus resulting in an increase in paracellular permeability. Overexpression of HuR exhibited an opposite effect on E-cadherin expression by preventing the translocation of E-cadherin mRNA to PBs and therefore prevented CUGBP1-induced repression of E-cadherin expression. Elevation of HuR also abolished the CUGBP1-induced epithelial barrier dysfunction. These findings indicate that CUGBP1 and HuR negate each other's effects in regulating E-cadherin translation by altering the recruitment of E-cadherin mRNA to PBs and play an important role in the regulation of intestinal barrier integrity under various pathophysiological conditions.

Chlamydia trachomatis is the etiological agent of the most commonly reported bacterial sexual transmitted infection (STI) in North America and Europe. The control of Chlamydia infection is hindered by the asymptomatic nature of initial infection but the consequence of untreated infection seriously threatens the reproductive health of young women. Unfortunately, there is no licensed vaccine for Chlamydia vaccine, in part due to our incomplete understanding of the immune response to Chlamydia urogenital infection. It has been well established that T cell-mediated immunity plays a dominant role in protective immunity against Chlamydia and thus the importance of B cells is somewhat underappreciated. Here, we summarize recent progress on understanding the role of B cells during Chlamydia genital tract infections and discuss how B cells and humoral immunity make an effective contribution to host defense against important intracellular pathogens, including Chlamydia.

Reninoma is an extremely rare renal tumor characterized by excessive renin secretion causing secondary hypertension and hypokalemia. Reninoma is a benign and highly manageable lesion if it is discovered early and removed surgically.We report six cases of reninoma and provide a literature review on this rare disease, highlighting the diagnostic evaluation and follow-up of each patient.Reninoma should be considered in young adults with elevated renin activity and refractory hypertension. Imaging studies and selective venous catheterization are often helpful in identifying the lesion. In most cases of reninoma presenting with renin-mediated hypertension, conservative surgical treatment should be considered to remove the small, superficial lesion.

To investigate the relationship between the different types of allergic rhinitis and anxiety.State-trait anxiety (State-Trait Anxiety Inventory, STAI) was adopted to 98 cases, moderate to severe persistent allergic rhinitis (PAR, male 43 cases, female 55 cases ) and 165 cases of moderate to severe intermittent allergic rhinitis (IAR, male 89 cases, female 76 cases ) and compared with the Chinese standard norm.SPSS 15.0 software was used to analyze the data.There was no significant difference in state anxiety (S-AI) and trait anxiety (T-AI) score (P(PAR): 0.411,0.724; P(IAR): 0.400,0.061) between male patients with allergic rhinitis (PAR and IAR) and the 1998 Chinese male norm. There was no significant difference (P(PAR): 0.503, P(IAR): 0.789) between female AR patients and normal in T-AI. The S-AI score was significantly higher in female AR patients than that in Chinese women norm scores (P(PAR) = 0.007, P(IAR) = 0.004). PAR and IAR showed no significant difference on T-AI and S-AI. (P value was 0.748 and 0.967).Female patients with allergic rhinitis can cause anxiety and continued, but there is no obvious anxiety potential in T-AI. The male patients do not show significantly different from normal people in terms of state and trait anxiety. And then, different types of allergic rhinitis have no significant correlation with anxiety.