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Intracoronary injection of pro-urokinase (Pro-UK) during percutaneous coronary intervention (PCI) seems to be a promising treatment in improving myocardial perfusion. In this systematic review and meta-analysis, we aimed at investigating the efficacy and safety of intracoronary Pro-UK injection during PCI in ST elevation myocardial infarction (STEMI) patients.A comprehensive literature searched on PubMed, Embase, Cochrane, Ovid-MEDLINE, Ovid-Embase, Ovid-Cochrane Databases and ClinicalTrials.gov from inception until June 1, 2022, in English only. The primary outcome was myocardial perfusion, including thrombolysis in myocardial infarction (TIMI) grades, corrected TIMI frame count (CTFC), TIMI myocardial perfusion grades (TMPG). The secondary outcomes were ST-segment resolution (STR), major adverse cardiovascular events (MACE), myocardial marker, cardiac function and hemorrhagic complications.We identified 5 studies (all RCTs) involving 761 participants. Under PCI procedure, compared with placebo, intracoronary Pro-UK injection may improve myocardial perfusion, including increasing the TIMI grades [odd ratio (OR) 0.46; 95% confidence interval (CI) 0.28-0.75; p = 0.002; I2 = 0%] , CTFC (OR -3.47; 95% CI [-5.60, -1.33]; p = 0.001; I2 = 0%) and TMPG (OR 0.17; 95% CI [0.06-0.44]; p = 0.0003; I2 = 0%), increase the rate of STR (OR 2.25; 95% CI [1.56-3.26]; p0.0001; I2 = 0%), reduce the incidence of MACE (OR 0.51; 95% CI [0.33-0.81]; p = 0.004; I2 = 0%) and reduce myocardial infarct size (CK, standardized mean difference [SMD] -0.45; 95% [CI] [-0.62, -0.28]; p0.00001; I2 = 10%. CK-MB, [SMD] -0.43; 95% CI [-0.68, -0.18]; p = 0.0007; I2 = 60%. cTnI, [SMD] -0.31; 95% CI [-0.46, -0.17]; p0.0001; I2 = 0%). Moreover, the treatment may improve the cardiac functions (LVFE, pooled mean difference [MD] 1.23; 95% CI [0.66-1.79]; p0.0001; I2 = 24%. LVEDd, pooled MD -0.13; 95% CI [-0.17, -0.09]; p0.00001; I2 = 0%). But there is no statistically significant difference between the Pro-UK group and placebo in the occurrence of hemorrhagic complications (OR 1.19; 95% CI [0.75-1.87]; p = 0.46; I2 = 0%).Intracoronary Pro-UK injection during PCI in STEMI patients is an effective and safe treatment to perform. The treatment may improve myocardial perfusion and rate of STR, as well as decreasing the incidence of MACE and myocardial infarct size. Importantly, the treatment may improve the cardiac functions and life quality. In the future, more multi-centered and massive sample studies are required.

The Coatomer protein complex subunit beta 2 (COPB2) is involved in the formation of the COPI coatomer protein complex and is responsible for the transport of vesicles between the Golgi apparatus and the endoplasmic reticulum. It plays an important role in maintaining the integrity of these cellular organelles, as well as in maintaining cell homeostasis. More importantly, COPB2 plays key roles in embryonic development and tumor progression. COPB2 is regarded as a vital oncogene in several cancer types and has been implicated in tumor cell proliferation, survival, invasion, and metastasis. Here, we summarize the current knowledge on the roles of COPB2 in cancer development and progression in the context of the hallmarks of cancer.

Studies have found that erectile dysfunction (ED) may be a short-term or long-term complication in coronavirus disease 2019 (COVID-19) patients, but no relevant studies have completed a pooled analysis of this claim. The purpose of the review was to comprehensively search the relevant literature, summarize the prevalence of ED in COVID-19 patients, assess risk factors for its development, and explore the effect of the COVID-19 infection on erectile function.Medline, Embase, and the Cochrane Library was performed from database inception until April 14, 2022. Heterogeneity was analyzed by χOur review included 8 studies, 4 of which functioned as a control group. There were 250,606 COVID-19 patients (mean age: 31-47.1 years, sample size: 23-246,990). The control group consisted of 10,844,200 individuals (mean age: 32.76-42.4 years, sample size 75-10,836,663). The prevalence of ED was 33% (95% CI 18-47%, ICOVID-19 patients have a high risk and prevalence of ED, mainly driven by anxiety. Attention should be paid to patient's erectile functioning when treating COVID-19.

Single-arm trial refers to a clinical trial design that does not set up parallel control group, adopts open design, and does not involve randomization and blind method. These features, on the one hand, speed up the process of clinical trials, significantly shorten the time to market and meet the needs of patients with advanced malignancies, but also lead to the uncertainty of single-arm clinical trials themselves. Recently, the US Food and Drug Administration held a meeting of the oncologic drug advisory committee to discuss six tumor indications that have been accelerated approved, which once again triggered the discussion of single-arm trials. The basis of accelerated approval by single-arm trial is actually a compromise on the level of evidence-based medical evidence requirements after assessing the benefit risk. Therefore, the sponsor should strictly grasp the applicable conditions of single-arm trial in anti-tumor drugs and conduct single-arm trial scientifically. Post-marketing clinical trial should be implement as early as possible to ensure the benefit of patients. Based on the characteristics of single-arm trial, combined with two guidance relevant to single-arm trial issued by National Medical Products Administration recently, this article is supposed to propose and summarize the strategy of single-arm trial supporting the marketing of anti-tumor drugs.单臂试验是指在临床试验设计时，不设立平行对照组，并采用开放设计，不涉及随机与盲法的一种临床试验设计。单臂试验的特征一方面加速了临床试验的进程，缩短了药品的上市时间，使晚期恶性肿瘤患者更快获得治疗药物，但同时也具有试验结果不够稳定的局限性。2021年4月，美国食品药品监督管理局召开肿瘤药物咨询委员会会议，对6项已通过单臂加速批准上市的肿瘤适应证进行讨论，再次引发了各界对单臂试验的讨论。单臂试验所支持的药品加速上市，实际是在评估了获益风险后，对循证医学证据级别要求进行了一定程度的妥协，因此，研发单位应严格把握单臂试验支持抗肿瘤药物附条件上市的适用条件，并科学开展单臂试验，同时，及早开展上市后确证性研究，以确保患者获益。文章基于单臂试验的特点，结合国家药品监督管理局发布的《单臂试验支持上市的抗肿瘤药进入关键试验前临床方面沟通交流技术指导原则》和《单臂试验支持上市的抗肿瘤药上市许可申请前临床方面沟通交流技术指导原则》，对单臂试验支持抗肿瘤药物上市策略提出思考与总结。.

1. Mycoplasma gallisepticum (MG) causes severe lung inflammation and cell damage by activating toll-like receptor (TLR) signalling, the nuclear factor-kappaB (NF-κB) pathway and pro-inflammatory cytokine gene expression. Baicalin (BA) is a flavonoid extracted from Scutellaria baicalensis, which possesses anti-inflammatory and anti-bacterial properties. This study investigated the effect of BA in MG-induced lung inflammation and its potential mechanism in MG-infected chicken embryo lungs and DF-1 cells.2. The histopathological examination result showed that BA treatment alleviated MG-induced lung pathological changes. In addition, CCK-8 and cell cycle assays showed that BA treatment inhibited MG-induced cell proliferation and cell cycle progression in DF-1 cells.3. The ELISA and RT-qPCR results demonstrated that BA treatment decreased the expression of interleukin-1beta (IL-1β), IL-6, and tumour necrosis factor-alpha (TNF-α) both in MG-infected chicken embryo lungs and DF-1 cells.4. The results revealed that BA inhibited mRNA expression levels of toll-like receptor-6 (TLR6), myeloid differentiation primary response gene-88 (MyD88) and nuclear factor-κB (NF-κB), and the nuclear translocation of NF-κB-p655. In conclusion, the results showed that BA has a protective effect against MG-induced lung inflammation in chicken by inhibiting the TLR6-mediated NF-κB signalling.

Bio-inspired polarization navigation is a promising navigation method inspired by insects’ autonomous foraging and homing behaviour. Many insects acquire their spatial orientation by sensing the polarization pattern of the skylight. We propose utilization of solar meridian in the polarized skylight as an orientation cue because of its significant features. Using its features, we then design and construct an imaging polarization navigation prototype. The prototype consists of a field-division polarization imaging sensor, the corresponding software, an interface, and the solar-meridian recognizing and measurement algorithm. The field-division polarization imaging sensor is the core component of the prototype and acquires polarized intensity images. To adapt to the demand of real-time on navigation system, we then propose an optimized real-time polarization image processing and pattern recognition algorithm based on Hough transform. The azimuth measurement accuracy of the sensor is then calibrated using a facility that is able to get higher azimuth accuracy by measurement of the star light. To verify the navigation capability of the developed system, we use a dynamic experiment, where the prototype is installed on the top of a vehicle and its navigation performance is compared with GNSS.

OBJECTIVE: To investigate the clinical characteristics of lower extremity arterial disease (LEAD) and its risk factors in patients with diabetic foot ulcer (DFU). METHODS: We retrospectively collected the clinical and follow-up data of 650 patients with DFU treated in the Department of Endocrinology and Metabolism of Nanfang Hospital between January, 2017 and December, 2019. We compared the data between patients who had LEAD and those without LEAD and used a multivariate logistic regression model to analyze the risk factors of LEAD in DFU patients. RESULTS: Among the 650 DFU patients, 470 (72.4%) had LEAD. The patients were followed up for a mean of 3.5 months, and the mean healing time of DFU was 2.55 months; healing of DFU occurred in 453 patients and 183 patients received amputation. The patients with LEAD and those without LEAD differed significantly in age, hospitalization costs, diastolic blood pressure (DBP), glycated hemoglobin, blood lipid levels, disease course, ankle brachial index, healing time, smoking history, clinical outcomes, Wagner grade and imaging results (P < 0.05). Multivariate logistic regression analysis identified age (OR=1.070, 95% CI: 1.049-1.091), smoking history (OR= 2.013, 95% CI: 1.268-3.195), and a decreased DBP (OR=0.980, 95% CI: 0.963-0.997) as independent risk factors for LEAD in DFU patients. A prolonged healing time was a prominent clinical feature of DFU complicated by LEAD. CONCLUSION: DFU patients have a high incidence of LEAD, which leads to high rates of disability and mortality and is associated with an advanced age, high smoking rate and longer healing time. A decreased DBP is also a risk factor for LEAD in DFU patients.

To evaluate the prognostic value of left atrial global longitudinal strain (LAGLS) in atrial fibrillation (AF) patients with mitral valve disease (MVD).In this single-centre retrospective study, 48 consecutive AF patients with MVD who underwent cardiac magnetic resonance imaging (CMRI) before surgery were enrolled. The LAGLS was assessed by cine-CMRI images and feature tracking (CMRI-FT) technique. Logistic regression and receiver operating characteristic (ROC) analysis were performed to identify the value of LAGLS in predicting atrial tachyarrhythmia recurrence after surgery.The LAGLS level of the total patients was 4.4% (interquartile range: 2.7-9.2%). LAGLS was significantly associated with many evaluated parameters of severity of disease including biventricular volumetric function, left atrial (LA) ejection fraction, and the European System for Cardiac Operative Risk Evaluation II score (all p0.05). Multivariate Cox analysis showed that LAGLS (hazard ratio = 0.52, 95% confidence interval [CI]: 0.31, 0.87; p=0.013) was an independent predictor of atrial tachyarrhythmia recurrence after adjustment for LA diameter, LA and biventricular ejection fraction, aetiology of MVD (rheumatic or degenerative), and surgical procedure (valve surgery alone or valve surgery combined with Maze IV). The optimal cut-off value of LAGLS was 4.1% for predicting recurrent atrial tachyarrhythmia (sensitivity 81.8%, specificity 78.4%) and the area under the ROC curve was 0.854 (95% CI: 0.711, 0.996, p0.001).CMRI-FT-derived LAGLS may act as a novel non-invasive imaging biomarker with which to evaluate the severity of disease and offer independent prognostic information for atrial tachyarrhythmia recurrence after surgery in AF patients with MVD.

We propose an unsupervised unimodal registration method based on Wasserstein Gan. Different from the existing registration methods based on deep learning, the proposed method can finish training without ground truth or preset similarity metrics. The network is composed of a generation network and a discrimination network. The generation network extracts the potential deformation fields between fixed images (positive images) and moving images, and predicts the registered images (negative images) by interpolation; the discrimination network then judges the similarity between the positive images and negative images that are input alternately, and feeds back the judgment result as a loss function to drive the network parameter update. Finally, through adversarial training, the registration image generated by the generation network deceives the discrimination network and the network converges. In the experiment, we randomly selected 30 cases of LPBA40 brain dataset, 25 cases of EMPIRE10 lung dataset and 15 cases of ACDC heart dataset as the training datasets, with 10 cases of LPBA40 brain dataset, 5 cases of EMPIRE10 lung dataset and 5 cases of ACDC heart dataset as the test datasets. The results of registration were compared with those obtained using Affine algorithm, Demons algorithm, SyN algorithm and VoxelMorph algorithm. The DICE coefficient (DSC) and the normalized correlation coefficient (NCC) evaluation index of the proposed algorithm were the highest, indicating a better registration accuracy of our method than Affine algorithm, Demons algorithm, SyN algorithm and the current unsupervised SOTA algorithm VoxelMorph.

OBJECTIVE: To investigate the application value of serum 25-hydroxy vitamin D [25(OH)D] in systemic lupus erythematosus (SLE). METHODS: Data of 158 patients with SLE in Department of Rheumatology and Immunology in the People's Hospital of Xinjiang Uygur Autonomous Region from July 2016 to July 2019. All the SLE patients were divided into two groups by SLE scores of the disease activity index (SLEADI): 59 cases of active group (SLEADI > 4), 99 cases of non-active group (SLEDAI ≤4). Fifty healthy people were selected as healthy control group. The patients' general information and their laboratory data including serum 25(OH)D levels were collected. Statistical methods used were t-test, Spearman's correalation analysis and Logistic regression analysis. RESULTS: (1) A total of 208 cases were included in this study. The level of 25(OH)D in SLE group [10.4(5.6, 15.8) μg/L] was significantly lower than that in healthy control group [25.5(22.8, 32.3) μg/L, P < 0.01]. 25(OH)D level in active SLE patients [6.2(3.7, 13.8) μg/L] was significantly lower than that in remission SLE patients [12.3(7.2, 16.7) μg/L, P < 0.01]. The serum 25(OH)D level in lupus nephritis [6.7 (4.4, 12.9) μg/L] was significantly lower than that in SLE without renal involvement [13.3 (7.4, 18.7) μg/L, P < 0.01]. (2) A significant negative correlation was demonstrated between the serum level of 25(OH)D and SLEDAI (r=-0.35, P < 0.01), and the 24h urinary protein excretion (r=-0.39, P < 0.01).Positive correlation was demonstrated between the serum level of 25(OH)D and C3 that decreased (r=0.249, P < 0.05). (3) Univariate analysis showed anti- dsDNA antibodies(ds-DNA), anti-Sm antibodies(Sm), IgG, C3, C4, erythrocyte sedimentation rate (ESR), 24h urinary protein quantification(24h-pro) and 25(OH)D were associated with disease activity in the SLE patients; Multivariate Logistic regression analysis showed that 25(OH)D was associated with the disease activity of the lupus patients. CONCLUSION: The decrease of vitamin D level is related to the disease activity of SLE patients, and may be related to lupus nephritis, which plays an important role in the occurrence and development of SLE.

A highly effective nicotine-degrading bacterial strain 1206 was isolated and identified as Pseudomonasfluorescens according to its morphological, physiological and biochemical characteristics and 16S rDNA sequence analysis. Strain P.fluorescens 1206 could utilize nicotine as the sole carbon and nitrogen source and degrade nicotine while growing in Luria-Bertani medium. This bacterium was able to remove about 33.8, 82.5 and 97.1% of nicotine with initial concentration of 1 g/L after 8, 16 and 24 h of incubation, respectively. This is the first report on the isolation and characterization of a strain of P. fluorescens with high-degrading nicotine ability. This finding may open the way to new biotechnological application of P. fluorescens to degradation of nicotine.

This paper discusses and compares deterministic and probabilistic approaches for assessing hosting capacity (HC) of distribution networks for connecting wind-based and PV-based distributed generation (DG). The presented approaches consider actual variations of solar and wind energy resources, supplied demands and dynamic thermal ratings (DTRs) of network components, based on available measurement data. The obtained results allow for a detailed analysis of the firm HC allocation for wind-based and PV-based DG in distribution networks, confirming that, due to implementation of DTRs, firm HC of wind DG is roughly twice the firm HC of PV DG.

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This paper presents a multi-stage optimal power flow (OPF) approach for efficient management of contingencies, in which dynamic thermal models of overhead lines and power transformers are used to evaluate maximum lead time (MLT) available to network operators to resolve violated post-contingency constraints. At the first stage, optimal settings of volt-var controls, such as transformers with on-load tap changers and shunt capacitors, are selected, taking into account voltage-dependent load models. The second stage provides optimal generation re-dispatch, including fast-start generators. At the final third stage, optimal load shedding is implemented to clear all remaining constraint violations. The OPF problem is solved by a hybrid metaheuristics method and illustrated on a modified IEEE 14-bus network. Obtained results demonstrate that presented method can help network operators to efficiently resolve all violated constraints within the available MLT.

International audience; This paper evaluates deterministic and probabilistic approaches for assessing hosting capacity (HC) of distribution networks for wind-based distributed generation (DG). The presented methodology considers variations of demands and DG power outputs, as well as dynamic thermal ratings (DTR) of network components. Deterministic approaches are based on a limited number of scenarios with minimum and maximum demands and DTR limits, while probabilistic approaches use simultaneous hourly values of all input parameters. The presented methodology has three stages. First, locational HC (LHC) of individual buses is calculated assuming connection of a single DG unit in the considered network. Afterwards, the LHC results are used to calculate network HC (NHC), assuming that DG units are connected at all network buses. Finally, busto-bus LHC-sensitivity factors are used to determine LHC and NHC for any number of DG units connected at arbitrary network buses.

Studies have demonstrated that long non-coding RNAs (lncRNAs) are important in the development and prognosis of prostate cancer. The aim of this study was to investigate the functions and mechanism of lnc-SNHG14 in prostate cancer.Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) or Western blot (WB) were performed to detect mRNA expressions of SNHG14 and miR-5590-3p, and the protein levels of Yin Yang-1 (YY1) in prostate cancer tissues, adjacent tissues, and cancer cell lines. The correlation analysis was used to analyze the correlations between SNHG14, miR-5590-3p, and YY1. Kaplan-Meier survival analysis was used to analyze the overall survival for prostate cancer patients. Cell Counting Kit-8 (CCK-8) assay was performed to measure cell proliferation ability and flow cytometry assay was used to detect cell apoptotic rate. Besides, transwell assay was used to measure cell invasion ability. In addition, WB was performed to measure protein expressions in prostate cancer cell lines. Finally, Luciferase reporter assay was performed to verify the binding sites between SNHG14 and miR-5590-3p, miR-5590-3p, and YY1.The results showed that SNHG14 was significantly increased in prostate cancer tissues and prostate cancer cell lines, which were related with advanced stage and poor diagnosis for prostate cancer patients. MiR-5590-3p was reduced in prostate cancer tissues and cell lines, which were negatively correlated with SNHG14. YY1 was found to be increased in prostate cancer tissues, which was negatively correlated with miR-5590-3p and positively correlated with SNHG14. Furthermore, SNHG14 knockdown inhibited cell proliferation, invasion, and promoted cell apoptosis in DU145 cells. In addition, protein expressions of Cyclin D1, Bcl-2, and N-cadherin were repressed, and the levels of Bax, Cleaved Caspase-3, and E-cadherin were increased. Besides, miR-5590-3p inhibition promoted cell proliferation and invasion, and inhibited apoptosis in DU145 cells. Importantly, Luciferase reporter assay proved that SNHG14 could directly sponge with miR-5590-3p, which could bind with YY1 and regulate the functions of cancer cell. Finally, we proved that SNHG14 regulated cell proliferation, cell apoptosis, and invasion via miR-5590-3p/ YY1 axis in prostate cancer.Above all, we found that SNHG14 was increased in prostate cancer patients, which was related with future diagnosis for prostate cancer patients. Of note, we discovered that SNHG14 could promote cell proliferation, invasion, and repress cell apoptosis via miR-5590-3p/YY1 axis in prostate cancer, which might provide a new target for treating prostate cancer.

Background Hypergonadotropic hypogonadism (HH) is characterized by low sex steroid levels and secondarily elevated gonadotropin levels with either congenital or acquired etiology. Genetic factors leading to HH have yet to be fully elucidated. Methods Here, we report on genome and transcriptome data analyses from a male patient with HH and history of growth delay who has an inherited deletion of chromosome Xq28. Expression analyses were done for this patient and his unaffected family members and compared to normal controls to identify dysregulated genes due to this deletion. Results Our patient’s Xq28 deletion is 44,806 bp and contains only two genes, FUNDC2 and CMC4. Expression of both FUNDC2 and CMC4 are completely abolished in the patient. Gene ontology analyses of differentially expressed genes (DEGs) in the patient in comparison to controls show that significantly up-regulated genes in the patient are enriched in Sertoli cell barrier (SCB) regulation, apoptosis, inflammatory response, and gonadotropin-releasing regulation. Indeed, our patient has an elevated follicle stimulating hormone (FSH) level, which regulates Sertoli cell proliferation and spermatogenesis. In his mother and sister, who are heterozygous for this deletion, X-chromosome inactivation (XCI) is skewed toward the deleted X, suggesting a mechanism to avoid FSH dysregulation. Conclusion Compared to the previously reported men with variable sized Xq28 deletions, our study suggests that loss of function of FUNDC2 and CMC4 results in dysregulation of apoptosis, inflammation, and FSH, and is sufficient to cause Xq28-associated HH.

The outbreak of 2019-novel coronavirus (2019-nCoV) infection poses a serious threat to global public health. Vaccination is an effective way to prevent the epidemic of the virus. 2019-nCoV along with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) belong to the same β-genus of coronavirus family. Basing on the previous experience and the technical platform of developing SARS-CoV and MERS-CoV vaccines, scientists from all over the world are working hard and quickly on the related fields. There are substantial progress in these fields including characterizing the 2019-nCoV virus, identification of candidate antigens and epitopes, establishment of animal models, characterizing the immune responses, and the design of vaccines. The development of 2019-nCoV vaccines covers all types: inactivated virus vaccine, recombinant protein vaccine, viral vector-based vaccine, mRNA vaccine, and DNA vaccine, et al. As of March 2020, two 2019-nCoV vaccines have entered phase I clinical trials. One is named as Ad5-nCoV developed by the Chinese Institute of Biotechnology of the Academy of Military Medical Sciences and Tianjin Cansino Biotechnology Inc. Ad5-nCoV is based on the replication-defective adenovirus type 5 as the vector to express 2019-nCoV spike protein. The another vaccine is mRNA-1273 developed by the National Institute of Allergy and Infectious Diseases and Moderna, Inc.. RNA-1273 is an mRNA vaccine expressing 2019-nCoV spike protein. Although the rapid development of 2019-nCoV vaccine, it still faces many unknown challenges, including the antigenic characteristics of the 2019-nCoV, the influence of antigenic variation, the protective immune response of host, the protection of the elderly population, and the downstream manufacturing process of the new vaccine. The safety and efficacy of vaccines are the first priority for vaccine development and should be carefully evaluated.新型冠状病毒（2019-nCoV）感染暴发流行对全球公众健康构成了严重威胁，疫苗接种是有效预防病毒感染流行的手段。2019-nCoV与急性呼吸综合征冠状病毒（SARS-CoV）和中东呼吸综合征冠状病毒（MERS-CoV）同属于β-冠状病毒。基于对SARS-CoV和MERS-CoV的了解，科学家对2019-nCoV病毒特征的研究、候选抗原及表位的鉴定、动物模型的建立、免疫应答的检测，疫苗的设计等工作取得了快速进展。新型冠状病毒疫苗（新冠疫苗）的研发也取得了快速进展，新冠疫苗类型几乎涵盖了目前疫苗研究的所有形式，包括灭活疫苗、重组蛋白疫苗、病毒载体疫苗、核酸疫苗（mRNA疫苗与DNA疫苗）等。至2020年3月，已有2项新冠疫苗进入了Ⅰ期临床试验，分别为我国军事医学科学院联合天津康希诺生物股份公司研发的基于腺病毒载体的重组新冠疫苗和美国Moderna公司的mRNA 疫苗，两种疫苗均以2019-nCoV的刺突蛋白为抗原靶标。同时，新冠疫苗研发仍面临着许多未知的挑战，如2019-nCoV病毒抗原特征、抗原变异、机体的保护性免疫应答特征以及对老年及基础病人群是否具有保护，新冠疫苗量产的生产工艺等方面仍需要更多的研究。疫苗研发具有其固有规律，在加快速度的同时，保证疫苗的安全性、有效性是必须的前提。.

Objective To investigate the effect of high-intensity focused ultrasound (HIFU) ablation for uterine fibroids on pregnancy. Design A retrospective observational study. Setting Department of Gynaecology in a single centre in China. Population Patients with uterine fibroids who wish to become pregnant. Methods Patients with uterine fibroids who wished become pregnant and have children, were treated using HIFU from April 2011 to March 2016 at Chongqing Haifu Hospital. Pregnancy outcomes were analysed. Main outcome measures Pregnancy outcomes after undergoing USgHIFU. Results After the HIFU treatment, the 78 patients had 80 pregnancies, in which 76 cases were natural pregnancies and four were test-tube pregnancies. Of the 78 patients who became pregnant, nine patients had complicated primary or secondary infertility before the HIFU treatment, 13 patients had had at least two miscarriages or missed miscarriages, one patient had had a stillbirth; none had undergone other special treatment. After the HIFU treatment, the average time to pregnancy was 5.6 ± 2.7 months. There were 15 cases of full-term normal delivery and 56 cases of caesarean, including three cases of premature caesarean. After the treatment, three patients had a miscarriage (one patient's progesterone level was lower than the normal value; and the other two miscarriages were for unknown reasons), two patients became pregnant 3 months after complete curettage of uterine cavity and had full-term normal deliveries, one patient planned to use contraception after complete curettage of the uterine cavity; and one patient had her labour induced (after 13-weeks pregnancy). The fetuses of all the patients developed well during both the pregnancy and child-bearing without uterine rapture or perinatal and postpartum complications. Conclusion HIFU treatment can effectively treat patients with uterine fibroids who wish to have children; it could significantly reduce the preparation period for pregnancy after the operation. It can also improve the fertility of patients with a history of infertility and abnormal pregnancy and child-bearing, with no additional obstetric risks. Tweetable abstract As a noninvasive therapeutic technique, HIFU safely can be used to treat patients with uterine fibroids who wish to become pregnant.

Background: Patients with relapsed/refractory myeloma continue to represent an unmet medical need, and this is especially true for those with deletion (del) 17p, who have an inferior prognosis. We previously reported the ability of HDP-101 to induce anti-proliferative and pro-apoptotic effects in myeloma cell lines and primary patient samples. HDP-101 showed enhanced efficacy against del 17p models, which are characterized by concurrent haploinsufficiency of RNA polymerase II subunit A (POLR2A), which is the target of amanitin. This occurred in conjunction with activation of the endoplasmic reticulum stress, and at least two arms of the unfolded protein response. Also, a single dose of HDP-101 was sufficient to induce cures in murine models of myeloma both with and without TP53 and/or POLR2A. Therefore, we sought to better understand the mechanisms of action of HDP-101 and its potential immunologic sequelae. Methods: Pre-clinical studies were performed using HDP-101, the unconjugated BCMA antibody, free α-Amanitin, and a non-targeting control Amanitin antibody drug conjugate in myeloma cell line models and in vivo. These included H929, MM1.S, and MOLP-8 TP53 wild-type (WT) lines and isogenic cells in which TP53 had been knocked out (KO) using genome editing techniques. To further model del 17p and POLR2A haploinsufficiency, POLR2A expression was knocked down using sequence-specific shRNAs. Tumor rechallenge experiments were performed after 100 days of tumor free survival in NOD.CB17-Prkdcscid/J mice with longitudinal monitoring of tumor growth kinetics. Results: HDP-101 induced immunogenic cell death (ICD) in myeloma cell lines as determined by increased expression of Calreticulin (CRT), Heat shock protein (HSP)-70, and release of High mobility group box 1 (HMGB1) by flow cytometry and Western blotting. Microscopic analysis of ICD upon treatment with HDP-101 in MM1.S cells showed a speckled arrangement of both CRT and HMGB1 on the cell surface. In addition, an increased ADP/ATP ratio was observed across three different cell lines in a TP53-independent manner suggestive of an operational ICD pathway. Using our current knowledge of ER stress activation and induction of ICD, we evaluated the combination of bortezomib and HDP-101 in H929, MM1.S, and MOLP-8 cells and primary samples. A significant loss of cellular viability (p Conclusions: Our results support the statement that HDP-101 is a novel anti-BCMA antibody drug conjugate that shows potent activity against drug-naïve and -resistant models of myeloma, and has the potential to show enhanced anti-tumor activity against del 17 p myeloma. Moreover, its mechanism of action involves both a direct cytotoxic effect, as well as the induction of immunogenic cell death, with the latter potentially leading to immunologic memory. These studies were supported by a Leukemia & Lymphoma Society Specialized Center of Research (SCOR-12206-17). Disclosures Jones: Asylia Therapeutics, Inc.: Current equity holder in private company, Patents & Royalties. Lee:Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Genentech: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Sanofi: Consultancy; Daiichi Sankyo: Research Funding; Regeneron: Research Funding; Genentech: Consultancy. Manasanch:Sanofi: Honoraria, Research Funding; Novartis: Research Funding; JW Pharma: Research Funding; Merck: Research Funding; Quest Diagnostics: Research Funding; Takeda: Honoraria; BMS: Honoraria; Glaxo Smith Kline: Honoraria; Adaptive Biotechnologies: Honoraria. Pahl:Heidelberg Pharma AG: Current Employment. Orlowski:Sanofi-Aventis, Servier, Takeda Pharmaceuticals North America, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen, Inc., AstraZeneca, BMS, Celgene, EcoR1 Capital LLC, Forma Therapeutics, Genzyme, GSK Biologicals, Ionis Pharmaceuticals, Inc., Janssen Biotech, Juno Therapeutics, Kite Pharma, Legend Biotech USA, Molecular Partners, Regeneron Pharmaceuticals, Inc.,: Honoraria, Membership on an entity's Board of Directors or advisory committees; Laboratory research funding from BioTheryX, and clinical research funding from CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Research Funding; STATinMED Research: Consultancy; Founder of Asylia Therapeutics, Inc., with associated patents and an equity interest, though this technology does not bear on the current submission.: Current equity holder in private company, Patents & Royalties.