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Abstract Objectives To compare the efficacy of nadroparin and fondaparinux sodium for prevention of deep vein thromboembolism (DVT) in lower extremities after total hip arthroplasty (THA) and total knee arthroplasty (TKA). Methods A total of 592 patients were enrolled in the study. Clinical data of patients who underwent total hip arthroplasty (THA) and total knee arthroplasty (TKA) in our hospital from December 2021 to September 2022 were retrospectively collected, which mainly included patients’ general information, surgery-related information, and DVT-related information. The patients were categorized into the nadroparin group(n = 278) and the fondaparinux sodium group(n = 314) according to the types of anticoagulants used. Anticoagulant therapy began 12–24 h after operation and continued until discharge. DVT prevalence between two groups was compared. The Statistical Package for Social Sciences (SPSS) software version 25 (SPSS, Armonk, NY, USA) was used for statistical analysis. Results The prevalence of DVT in the nadroparin group and the fondaparinux sodium group was 8.3% (23/278) and 15.0% (47/314), respectively(p = 0.012). Statistical analysis showed that nadroparin group showed a lower prevalence of thrombosis than fondaparinux group (OR = 1.952, P = 0.012). Subgroup analyses showed that nadroparin group had a lower prevalence of DVT than fondaparinux group in some special patients groups such as female patients (OR = 2.258, P = 0.007), patients who are 65–79 years old (OR = 2.796, P = 0.004), patients with hypertension (OR = 2.237, P = 0.042), patients who underwent TKA (OR = 2.091, P = 0.011), and patients who underwent combined spinal-epidural anesthesia (OR = 2.490, P = 0.003) (P

Abstract The decline of endothelial autophagy is closely related to vascular senescence and disease, although the molecular mechanisms connecting these outcomes in vascular endothelial cells (VECs) remain unclear. Here, we identify a crucial role for CD44, a multifunctional adhesion molecule, in controlling autophagy and ageing in VECs. The CD44 intercellular domain (CD44ICD) negatively regulates autophagy by reducing PIK3R4 and PIK3C3 levels and disrupting STAT3-dependent PtdIns3K complexes. CD44 and its homologue clec-31 are increased in ageing vascular endothelium and Caenorhabditis elegans, respectively, suggesting that an age-dependent increase in CD44 induces autophagy decline and ageing phenotypes. Accordingly, CD44 knockdown ameliorates age-associated phenotypes in VECs. The endothelium-specific CD44ICD knock-in mouse is shorter-lived, with VECs exhibiting obvious premature ageing characteristics associated with decreased basal autophagy. Autophagy activation suppresses the premature ageing of human and mouse VECs overexpressing CD44ICD, function conserved in the CD44 homologue clec-31 in C. elegans. Our work describes a mechanism coordinated by CD44 function bridging autophagy decline and ageing.

Sea ice surface temperature (IST) is an important indicator of environmental changes in the Arctic Ocean. In this study, the relative performance of four mainstream IST records, i.e. airborne IST, infrared radiometer measured IST (IR IST), longwave radiation derived IST (LWR IST), and snow and ice mass balance array buoy derived IST (Buoy IST), were evaluated against the MODIS IST product. Bias, standard deviation (STD), and root mean square error (RMSE) were used to evaluate the data quality. Results revealed that airborne IST had the best accuracy, which was 0.21 K colder than MODIS IST, with STD of 1.46 K and RMSE of 1.47 K. Ground-based ISTs were biased with each other but all warmer than the MODIS IST. The IR IST had the best overall accuracy (bias = 0.55 K; STD = 1.52 K; RMSE = 1.61 K), while the LWR IST was the noisiest measurement with the largest outlier data percent. Besides, co-located IR and LWR ISTs were more consistent than any type of evaluated IST against MODIS IST (correlation coefficient = 0.99). Airborne and IR ISTs are thus the premier choice for monitoring the rapidly changing Arctic sea ice, together with satellite observations.

Objective Neuropathic pain (NP) plays an important role in patients with knee osteoarthritis (KOA). However, the prevalence of NP at different treatment stages including outpatient, awaiting and after total knee arthroplasty (TKA) have not been compared. The understanding of this issue and identify risk factors can help physicians develop individualized strategies to manage the pain of KOA. Therefore, the aim of the study is to investigate the prevalence and risk factors of NP at different treatment stages of KOA. Methods Patients diagnosed as KOA between August 2016 and August 2020 were enrolled in this cross‐sectional study and divided into three groups according to treatment stage, including outpatient stage, awaiting TKA stage (pre‐TKA) and after TKA stage (post‐TKA). A numeric rating scale (NRS) and PainDETECT questionnaire were used to evaluate nociceptive pain and NP. Patient demographics, radiological assessments using Kellgren–Lawrence (K‐L) grade, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were analyzed. Data analysis and statistics were processed using SPSS 20.0 and examined by ANOVA with/without Bonferroni correction or Kruskal–Wallis test. A chi‐square test was used to determine cross‐table data and calculate the odds ratio (OR) value. Results Of the 921 patients, the prevalence of possible and likely NP was 17.5% (56/320) and 2.5% (8/320) in the pre‐TKA group compared with 3.4% (8/233) and 0.4% (1/233) in the outpatient group and 1.4% (5/368) and 0.5% (2/368) in the post‐TKA group, respectively. In the pre‐TKA group, higher NRS (NRS >3; OR = 10.65, 95% CI: 3.25–34.92, P 10; OR = 4.88, 95% CI: 2.38–10.01, P 3) and WOMAC pain scores (score > 10) are risk factors of NP.

Abstract Objective Over the years, microRNAs (miRNAs) have been involved in the pathogenesis of rheumatoid arthritis (RA). We aim to investigate the role of human umbilical cord mesenchymal stem cells (HUCMSCs)-derived exosomal miR-140-3p in RA development. Methods Exosomes(exo) were isolated from human umbilical cord-derived mesenchymal stem cells (HUCMSCs), and this isolation was followed by the transfer of miR-140-3p. RA rat models were constructed by collagen II adjuvant and respectively treated with HUCMSCs-exo or HUCMSCs-exo carrying miR-140-3p mimic/inhibitor, and expression of miR-140-3p and serum- and glucocorticoid-inducible kinase 1 (SGK1) was assessed. Then, RA score and inflammation scoring, fibrosis degree and apoptosis, serum inflammatory response and oxidative stress in joint tissues were determined. The RA synovial fibroblasts (RASFs) were extracted from rats and identified. Conducted with relative treatment, the migration, proliferation and apoptosis in RASFs were determined. Results MiR-140-3p was decreased while SGK1 was increased in RA rats. HUCMSCs-exo or upregulated exosomal miR-140-3p improved pathological changes and suppressed inflammation, oxidative stress and fibrosis in RA rats, and also constrained and RASF growth. Overexpression of SGK1 reversed the inhibition of RASF growth caused by overexpression of miR-140-3p. Conclusion Upregulated exosomal miR-140-3p attenuated joint injury of RA rats by silencing SGK1. This research provided further understanding of the role of exosomal miR-140-3p in RA development.

Accurate retrieval of ice surface temperature (IST) over the Arctic ice-water mixture zone (IWMZ) is significantly essential for monitoring the change of the polar sea ice environment. Previous researchers have focused on evaluating the accuracy of IST retrieval in pack ice regions, possibly on account of the availability of in situ measurement data. Few of them have assessed the accuracy of IST retrieval on IWMZ. This study utilized Landsat 8/TIRS and Operation IceBridge observations (OIB) to evaluate the accuracy of the current IST retrieval method in IWMZ and proposed an adjustment method for improving the overall accuracy. An initial comparison shows that Landsat 8 IST and OIB IST have minor differences in the pack ice region with RMSE of 0.475 K, MAE of 0.370 K and cold bias of −0.256 K. In the thin ice region, however, the differences are more significant, with RMSE of 0.952 K, MAE of 0.776 K and warm bias of 0.703 K. We suggest that this phenomenon is because the current ice-water classification method misclassified thin ice as water. To address this issue, an adjusted method is proposed to refine the classification of features within the IWMZ and thus improve the accuracy of IST retrieval using Landsat 8 imagery. The results demonstrate that the accuracy of the retrieved IST in the two cases was improved in the thin ice region, with RMSE decreasing by about 0.146 K, Bias decreasing by about 0.311 K, and MAE decreasing by about 0.129 K. After the adjustment, high accuracy was achieved for both pack ice and thin ice in IWMZ.

Ciprofloxacin is ubiquitous and poses a potential threat to aquatic ecosystems. However, the comprehensive effect of prolonged ciprofloxacin exposure on the submerged clonal plant Vallisneria natans (Lour.) Hara remains unknown. Growth and physiological responses in V. natans exposed to ciprofloxacin at concentrations of 0, 0.05, 0.25, 1.25, 2.5, 5 and 10 mg/L were repeatedly evaluated on Days 7, 14, 28, 42 and 56. V. natans maintained good growth properties under 0.05–0.25 mg/L ciprofloxacin treatments, while the inhibition effect on plant growth induced by higher-concentration treatments increased over time. The IC50 values of ciprofloxacin for growth endpoints ranged from 1.6 mg/L to 5.3 mg/L and displayed time-dependent decreases. Pigment contents were significantly stimulated by ciprofloxacin on Day 7 but decreased to varying degrees as the exposure time was extended. Soluble protein and hydrogen peroxide content rose significantly over the first 14 days of treatment with 0.25–10 mg/L ciprofloxacin but decreased under 1.25–10 mg/L ciprofloxacin treatments since Day 28. Antioxidants including superoxide dismutase, catalase, guaiacol peroxidase, ascorbate peroxidase and proline functioned well in mitigating oxidative stress under different ciprofloxacin concentrations, lowering the comprehensive toxic effects of ciprofloxacin on V. natans during the period from Day 14 to Day 42, as evidenced by decreased IBR (integrated biomarker response) values. However, the toxic pressure of ciprofloxacin on V. natans peaked on Day 56. These findings suggest that exposure time can influence the responses of V. natans exposed to ciprofloxacin and that IBR can be employed to evaluate the integrated impacts of prolonged ciprofloxacin contamination in aquatic settings.

10-Hydroxydec-2-enoic acid (10-HDA), an unsaturated hydroxyl fatty acid from the natural food royal jelly, can protect against cell and tissue damage, yet the underlying mechanisms are still unexplored. We hypothesized that the neutralization of the hydroxyl free radical (•OH), the most reactive oxygen species, is an important factor underlying the cytoprotective effect of 10-HDA. In this study, we found that the •OH scavenging rate by 10-HDA (2%, g/ml) was more than 20%, which was achieved through multiple-step oxidization of the –OH group and C=C bond of 10-HDA. Moreover, 10-HDA significantly enhanced the viability of vascular smooth muscle cells (VSMCs) damaged by •OH (P < 0.01), significantly attenuated •OH-derived malondialdehyde production that represents cellular lipid peroxidation (P < 0.05), and significantly increased the glutathione levels in •OH-stressed VSMCs (P < 0.05), indicating the role of 10-HDA in reducing •OH-induced cytotoxicity. Further proteomic analyses of VSMCs identified 195 proteins with decreased expression by •OH challenge that were upregulated by 10-HDA rescue and were primarily involved in protein synthesis (such as translation, protein transport, ribosome, and RNA binding) and energy metabolism (such as fatty acid degradation and glycolysis/gluconeogenesis). Taken together, these findings indicate that 10-HDA can effectively promote cell survival by antagonizing •OH-induced injury in VSMCs. To the best of our knowledge, our results provide the first concrete evidence that 10-HDA-scavenged •OH could be a potential pharmacological application for maintaining vascular health.

Abstract Ovarian cancer (OC) causes more deaths than any other gynecological cancer. Many cellular pathways have been elucidated to be associated with OC development and progression. Specifically, the insulin-like growth factor 1 receptor/insulin receptor substrate 1 (IGF1R/IRS1) pathway participates in OC development. Moreover, accumulating evidence has shown that microRNA deregulation contributes to tumor initiation and progression. Here, our study aimed to investigate the molecular functions and regulatory mechanisms of miR-150, specifically, in OC. We found that the expression of miR-150-5p/3p and their precursor, mir-150, was downregulated in OC tissues; lower mir-150 levels were associated with poor OC patient outcomes. Ectopic mir-150 expression inhibited OC cell growth and metastasis in vitro and in vivo. Furthermore, both IRS1 and IGF1R were confirmed as direct targets of miR-150-5p/3p, and the miR-150-IGF1R/IRS1 axis exerted antitumor effects via the PI3K/AKT/mTOR pathway. Forkhead box protein 3 (FoxP3) positively regulated the expression of miR-150-5p/3p by binding to the mir-150 promoter. In turn, the PI3K/AKT/mTOR pathway downregulated FoxP3 and miR-150-5p/3p. Taken together, these findings indicate that a complex FoxP3-miR-150-IGF1R/IRS1-PI3K/AKT/mTOR feedback loop regulates OC pathogenesis, providing a novel mechanism for miR-150 as a tumor suppressor miRNA in OC.

Thermodynamic parameters play a crucial role in determining polar sea ice thickness (SIT); however, modeling their relationship is difficult due to the complexity of the influencing mechanisms. In this study, we propose a self-attention convolutional neural network (SAC-Net), which aims to model the relationship between thermodynamic parameters and SIT more parsimoniously, allowing us to estimate SIT directly from these parameters. SAC-Net uses a fully convolutional network as a baseline model to detect the spatial information of the thermodynamic parameters. Furthermore, a self-attention block is introduced to enhance the correlation among features. SAC-Net was trained on a dataset of SIT observations and thermodynamic data from the 2012–2019 freeze-up period, including surface upward sensible heat flux, surface upward latent heat flux, 2 m temperature, skin temperature, and surface snow temperature. The results show that our neural network model outperforms two thermodynamic-based SIT products in terms of accuracy and can provide reliable estimates of SIT. This study demonstrates the potential of the neural network to provide accurate and automated predictions of Arctic winter SIT from thermodynamic data, and, thus, the network can be used to support decision-making in certain fields, such as polar shipping, environmental protection, and climate science.

Abstract Monascus pigments (MPs) with different color characteristics, produced by submerged fermentation of Monascus purpureus M9, have potential application in food industry. In the present study, the effects and regulatory mechanisms of ammonium nitrate (AN) on the color characteristics of MPs were investigated. The concentration of intracellular pigments was significantly decreased when subjected to AN. The hue and lightness value indicated AN altered the total pigments appearance from original red to orange. The HPLC analysis for six major components of MPs showed that the production of rubropunctatin or monascorubrin, was significantly reduced to the undetectable level, whereas the yields of monascin, ankaflavin, rubropunctamine and monascorubramine, were apparently increased with AN supplement. To be noted, via real-time quantitative PCR strategy, the expression level of mppG, closely relative to orange pigments biosynthesis, was significantly down-regulated. However, the expression of mppE, involved in yellow pigments pathway, was up-regulated. Moreover, the broth pH value was dropped to 2.5–3.5 in the fermentation process resulted from AN treatment, along with the increased extracellular polysaccharide biosynthesis. Taken together, the change of MPs categories and amounts by AN might be the driving force for the color characteristics variation in M. purpureus M9. The present study provided useful data for producing MPs with different compositions and modified color characteristics.

Abstract Objectives A pneumonia associated with 2019 novel coronavirus (2019-nCoV, subsequently named SARS-CoV2) emerged worldwide since December, 2019. We aimed to describe the epidemiological characteristics of 2019 coronavirus disease (COVID-19) in Shaanxi province of China. Results 1. Among the 245 patients, 132 (53.9%) were males and 113 (46.1%) were females. The average age was 46.15 ± 16.43 years, ranging from 3 to 89 years. 2. For the clinical type, 1.63% (4/245) patients were mild type, 84.90% (208/245) were moderate type, 7.76% (19/245) were severe type, 5.31% (13/245) were critical type and only 0.41% (1/245) was asymptomatic. 3. Of the 245 patients, 116 (47.35%) were input case, 114 (46.53%) were non-input case, and 15 (6.12%) were unknown exposure. 4. 48.57% (119/245) cases were family cluster, involving 42 families. The most common pattern of COVID-19 family cluster was between husband and wife or between parents and children.

Objective To compare medial pivot (MP) prostheses to two types of posterior‐stabilized (PS) prostheses (NexGen and NRG) in terms of patient satisfaction, causes of dissatisfaction, and risk factors for dissatisfaction after total knee arthroplasty (TKA). Methods A total of 453 patients who underwent primary TKA by one senior surgeon from August 2016 to August 2018 were investigated in a retrospective study, including 121, 219, and 113 patients in the MP, NexGen, and NRG groups, respectively. The mean age and follow‐up time of patients were 70.82 ± 7.06 years and 20.64 ± 3.88 months. A survey was designed and responses were collected by telephone, WeChat, and outpatient follow up. Patient satisfaction, causes of dissatisfaction, post‐TKA pain on a numeric rating scale (NRS), and range of motion (ROM) were compared among groups, and risk factors were investigated. Patient satisfaction included a five‐level satisfaction rating (very satisfied, satisfied, neutral, dissatisfied, or very dissatisfied), with five options for causes of dissatisfaction (persistent pain, limited ROM, knee instability, asthenia, and/or other factors). Results Overall, 89.84% of patients were satisfied with the results of primary TKA. There were no significant differences among the three groups regarding the side of the operation, the length of hospitalization in days, or the average follow‐up time. Patient satisfaction was similar among the MP (87.38%), NexGen (89.89%), and NRG groups (90.32%). Persistent pain after TKA was the major cause of dissatisfaction (32/40), but no difference in the frequency of this complaint was found among the groups (P = 0.663). The NRS score (P = 0.598) and the ROM (P = 0.959) of the MP group were not significantly different from those of the NexGen and NRG groups. Gender, length of hospitalization, and follow‐up time were all uncorrelated with patient satisfaction, but age showed a very weak correlation with patient satisfaction (r = 0.110, P = 0.033). Moreover, the NRS score (r = 0.459, P < 0.000) and the ROM (r = −0.175, P = 0.001) were significantly correlated with patient dissatisfaction. The odds ratio of dissatisfaction was 6.37 (P

Abstract Background Inflammatory mediators in the synovial fluid (SF) play critical roles in the initiation and development of pain in knee osteoarthritis (KOA). However, data for inflammatory marker expression are conflicting, and the role of SF inflammatory mediators in neuropathic pain is not clear. Therefore, the aim of this study was to identify SF inflammatory mediators associated with nociceptive and neuropathic pain in KOA. Methods Levels of IL-1β, IL-6, TNF-α, macrophage colony-stimulating factor, MMP-3, MMP-13, metalloproteinase with thrombospondin motifs 5, calcitonin gene-related peptide, neuropeptide Y, substance P and bradykinin were measured using enzyme-linked immunosorbent assays in 86 patients. Nociceptive pain was assessed using the numeric rating scale (NRS), visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. Neuropathic pain was determined using the PainDETECT questionnaire. Moreover, knee function was evaluated by the WOMAC score and range of motion (ROM) assessments. Radiological grade was defined using the Kellgren-Lawrence (K-L) grading scale. Results Pain scores measured using different methods correlated highly with each other. A worse K-L grade and knee function were associated with worse pain. Expression of IL-1β and IL-6 was increased in the early stage compared with the late stage. The NRS score correlated positively with age, K-L grade, and the WOMAC score and negatively with ROM and TNF-α expression. The VAS correlated positively with age, K-L grade, and the WOMAC score but negatively with ROM and levels of IL-1β, IL-6 and TNF-α. The WOMAC pain score did not correlate with any of the inflammatory mediators measured; it correlated only with ROM. The PainDETECT score correlated only with the WOMAC score. Expression of other inflammatory mediators did not correlate with any of the pain scores. Conclusions IL-1β, IL-6 and TNF-α play critical roles in pain in the early stage of KOA and correlate with pain. The catabolic enzymes and neuropeptides measured do not correlate with nociceptive and neuropathic pain. New biomarkers related to pain in the late stage need to be further investigated.

The accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) has been described in many cancers. In our previous studies, we have identified cancer risk and outcome associated SNPs in the D-loop of malignant fibrous histiocytoma (MFH). In the present study, we investigated the SNPs in the D-loop of mitochondria DNA (mtDNA) for their association with age-at-onset, metastasis, and relapse using a population-based series of MFH patients. Our data showed that the SNP site of nucleotide 16304 T/C was associated with age-at-onset using the Kaplan–Meier method and compared by the log-rank test. Meanwhile, allele 152C genotype was identified to be significantly associated with a high metastasis rate in MFH patients. In addition, patients with allele 16266C were proven to have a higher relapse rate compared with 16266T at a statistically significant level. Finally, we performed a multivariate analysis with the Cox proportional hazards model. The age-at-onset of patients with the minor allele C genotype was significantly earlier than that of patients with the T genotype at the 16304 site. In summary, the analysis of genetic polymorphisms in the D-loop may help to identify patient subgroups at a high risk of early onset, high metastasis and relapse rate in MFH, thereby helping to refine therapeutic decisions.

Lobaplatin is a third-generation platinum-based antineoplastic agent and is widely used for osteosarcoma treatment before and after tumor removal. However, treatment failure often results from lobaplatin drug resistance. In our study, we found that SaOS-2 and SOSP-9607 osteosarcoma cells became less sensitive to lobaplatin after treatment with exogenous interleukin (IL)-6. Quantitative proteomic analysis was performed to elucidate the underlying mechanism in SaOS-2 osteosarcoma cells. Cells were divided into a control group (CG), a lobaplatin treatment group (LG), a recombinant human IL-6 (rhIL-6), and a lobaplatin treatment group (rhILG). We performed three biological replicates in each group to compare the differential protein expression between groups using a tandem mass tag (TMT) labeling technology based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 1,313 proteins with significant differential expression was identified and quantified. The general characteristics of the significantly enriched proteins were identified by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and protein–protein interaction (PPI) analysis was conducted using IntAct and STRING. In total, 31 proteins were further verified by parallel reaction monitoring (PRM), among which ras GTPase-activating protein-binding protein 1 (G3BP1), fragile X mental retardation syndrome-related protein 1 (hFXR1p), and far upstream element-binding protein 1 (FUBP1) were significantly differentially expressed. Immunohistochemistry results showed that these three proteins are highly expressed in specimens from platinum-resistant osteosarcoma patients, while the proteins are negatively or weakly expressed in specimens from platinum-sensitive osteosarcoma patients. The immunofluorescence staining results were in accord with the immunohistochemistry staining results. siRNA knockdown of FUBP1 showed a strikingly decreased IC50 value for lobaplatin in FUBP1-silenced cells, which verified the role of FUBP1 in the drug susceptibility of osteosarcoma and the potential therapeutic value for increasing the sensitivity to lobaplatin. This is the first proteomic study on a rhIL-6 intervention before lobaplatin treatment in osteosarcoma cells.

Dome A is the summit of the Antarctic plateau, where the Chinese Kunlun inland station is located. Due to its unique location and high altitude, Dome A provides an important observatory site in analyzing global climate change. However, before the arrival of the Chinese Antarctic expedition in 2005, near-surface air temperatures had not been recorded in the region. In this study, we used meteorological parameters, such as ice surface temperature, radiation, wind speed, and cloud type, to build a reliable model for air temperature estimation. Three models (linear regression, random forest, and deep neural network) were developed based on various input datasets: seasonal factors, skin temperature, shortwave radiation, cloud type, longwave radiation from AVHRR-X products, and wind speed from MERRA-2 reanalysis data. In situ air temperatures from 2010 to 2015 were used for training, while 2005–2009 and 2016–2020 measurements were used for model validation. The results showed that random forest and deep neural network outperformed the linear regression model. In both methods, the 2005–2009 estimates (average bias = 0.86 °C and 1 °C) were more accurate than the 2016–2020 values (average bias = 1.04 °C and 1.26 °C). We conclude that the air temperature at Dome A can be accurately estimated (with an average bias less than 1.3 °C and RMSE around 3 °C) from meteorological parameters using random forest or a deep neural network.

Abstract Background Endometriosis is a chronic gynecological disease that is characterized by the presence of endometrial tissue outside the uterine cavity. The main symptoms include dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility. These symptoms impair the lives of most of the women suffering from the disease. Surgical resection of endometriotic lesions is an effective means of treating dysmenorrhea, but the risk of recurrence is high. Western medicine has limited use for treating it due to side effects and ineffectiveness. The purpose of this study is to verify the effectiveness and safety of acupuncture. Methods/design This trial will be carried out in four parts. A total of 106 eligible patients with pelvic pain related to endometriosis will be randomly assigned into two groups, in a 1:1 ratio, as the treatment group or the control group. The participants assigned to the treatment group will be treated with acupuncture treatment at Guanyuan (CV4), Sanyinjiao (SP6), Taichong (LR3), Zhaohai (KI6) and Qichong (ST30) while the control group will receive acupuncture at non-acupoints. The trial will include three menstrual cycles of treatment and three menstrual cycles of follow-up. The primary outcome is pelvic pain that will be assessed by means of a 10-cm visual analog scale (VAS). At each stage, we will evaluate the safety of the acupuncture treatment. Discussion The study will compare the effectiveness and safety of acupuncture with comfort needles on pelvic pain related to endometriosis in the hope of providing significant evidence for using acupuncture on pelvic pain related to endometriosis. Trial registration ClinicalTrials.gov, ID: NCT03125304. Registered on 30 April 2017.

miRNA biogenesis enzyme Drosha cleaves double-stranded primary miRNA by interacting with double-stranded RNA binding protein DGCR8 and processes primary miRNA into precursor miRNA to participate in the miRNA biogenesis pathway. The role of Drosha in vascular smooth muscle cells (VSMCs) has not been well addressed. We generated Drosha conditional knockout (cKO) mice by crossing VSMC-specific Cre mice, SM22-Cre, with Drosha (loxp/loxp) mice. Disruption of Drosha in VSMCs resulted in embryonic lethality at E14.5 with severe liver hemorrhage in mutant embryos. No obvious developmental delay was observed in Drosha cKO embryos. The vascular structure was absent in the yolk sac of Drosha homozygotes at E14.5. Loss of Drosha reduced VSMC proliferation in vitro and in vivo. The VSMC differentiation marker genes, including αSMA, SM22, and CNN1, and endothelial cell marker CD31 were significantly downregulated in Drosha cKO mice compared to controls. ERK1/2 mitogen-activated protein kinase and the phosphatidylinositol 3-kinase/AKT were attenuated in VSMCs in vitro and in vivo. Disruption of Drosha in VSMCs of mice leads to the dysregulation of miRNA expression. Using bioinformatics approach, the interactions between dysregulated miRNAs and their target genes were analyzed. Our data demonstrated that Drosha is required for VSMC survival by targeting multiple signaling pathways.

In this paper, linear navigation law is studied in depth and we suggest an efficient, practical and simple approach for nonholonomic mobile robot navigation under velocity vector control based on the linear navigation law. First of all, an obstacle is equivalent to a velocity vector when detected by a robot's sensory system according to the relative distant and relative direction between the robot and the obstacle. Then the vector sum of all obstacles' equivalent velocity vectors (OEVVs) and the linear navigation velocity vector (LNVV) derived from the linear navigation law drives the robot to reach the desired goal position without colliding with any obstacle in the robot's workspace. Furthermore, during the process of driving the mobile robot under the resultant velocity vector, a set of strategies for velocity and acceleration constraints (VAC) is devised to make kinematic behaviours of the mobile robot more practical. Finally, to validate the effectiveness and superiority, extensive simulation results with no obstacles, a single obstacle and multiple obstacles are provided.