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The basic body plan of the mammalian embryo is established through gastrulation, a pivotal early postimplantation event during which the three major germ layers (endoderm, ectoderm, and mesoderm) are specified with cellular and spatial diversity. Despite its basic and clinical importance, human embryo development from peri-implantation to gastrulation remains shrouded in mystery. Recent advances in the elongated in vitro culture of rodent and non-primate embryos and the construction of embryo-like structures have helped to improve understanding of the mechanisms of human early embryonic development. Here, we review the recent advances and possible future directions in the development of in vitro models to better understand human embryogenesis from peri-implantation to gastrulation.

Background Nasojejunal tube (NJT) feeding has demonstrated value in reducing pneumonia in critically ill adults who require enteral nutritional (EN) support. This study discusses whether EN support via nasojejunal tube (NJT) feeding is more cost-effective than nasogastric tube (NGT) feeding in reducing pneumonia. Methods A decision tree model was created. The analysis was based on data from a health care provider in China. Model inputs were derived from published data. The endpoints included incremental cost per pneumonia infection avoided, incremental cost-effectiveness ratio (ICER), net monetary benefit (NMB) and incremental net monetary benefit (INMB) associated with prevention of pneumonia. The uncertainty was assessed through one-way and probabilistic sensitivity analysis. Results The base case analysis showed that EN support via NJT feeding resulted in 0.7453 quality-adjusted life years (QALYs) at a cost of $3018.83 compared to NGT feeding, which resulted in 0.7354 QALYs at a cost of $4788.76. NJT feeding was better than NGT feeding, providing an INMB of $2,075.09 and an ICER of $-178,813.96 per QALY gained, and the cost per pneumonia infection prevented was $16,808.51. The probabilistic sensitivity analysis indicated that NJT feeding was more cost-effective in 83.4% of the cases, with a cost below the WTP threshold. The NMB and INMB estimation for different WTP thresholds also indicated that NJT feeding is the optimal strategy. Conclusions EN support via NJT feeding was a more cost-effective strategy than NGT feeding in preventing pneumonia in critically ill adults. This article is protected by copyright. All rights reserved.

The global coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused severe morbidity and mortality in humans. It is urgent to understand the function of viral genes. However, the function of open reading frame 10 (ORF10), which is uniquely expressed by SARS-CoV-2, remains unclear. In this study, we showed that overexpression of ORF10 markedly suppressed the expression of type I interferon (IFN-I) genes and IFN-stimulated genes. Then, mitochondrial antiviral signaling protein (MAVS) was identified as the target via which ORF10 suppresses the IFN-I signaling pathway, and MAVS was found to be degraded through the ORF10-induced autophagy pathway. Furthermore, overexpression of ORF10 promoted the accumulation of LC3 in mitochondria and induced mitophagy. Mechanistically, ORF10 was translocated to mitochondria by interacting with the mitophagy receptor Nip3-like protein X (NIX) and induced mitophagy through its interaction with both NIX and LC3B. Moreover, knockdown of NIX expression blocked mitophagy activation, MAVS degradation, and IFN-I signaling pathway inhibition by ORF10. Consistent with our observations, in the context of SARS-CoV-2 infection, ORF10 inhibited MAVS expression and facilitated viral replication. In brief, our results reveal a novel mechanism by which SARS-CoV-2 inhibits the innate immune response; that is, ORF10 induces mitophagy-mediated MAVS degradation by binding to NIX.

Background: The aim of the study was to screen biomarkers related to clear cell renal cell carcinoma (ccRCC) progression and prognosis. Methods: 1,026 ccRCC-related genes were dug from 494 ccRCC samples in TCGA based on weighted gene co-expression network analysis, and 7 modules were identified. Afterward, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted on modules of interest. Genes in these modules were taken as the input to construct a protein-protein interaction network. Thereafter, 30 genes with the highest connectivity were taken as core genes. Univariate Cox regression, LASSO Cox regression, and multivariate Cox regression analyses were performed on core genes. Univariate and multivariate Cox regression analyses were performed on patients’ clinical characteristics and risk scores. Results: Stage displayed significantly strong correlations with green module and red module (p < 0.001). Genes in modules participated in biological functions including T-cell proliferation and regulation of lymphocyte activation. GSEA showed that high- and low-risk groups exhibited significant enrichment differences in pathways related to immunity, cell migration, and invasion. Immune infiltration analysis also presented a strong correlation between the expression of these 8 genes and immune cell infiltration in ccRCC samples. It was displayed that risk score could be an independent factor to assess patients’ prognosis. Conclusion: We determined biomarkers relevant to ccRCC progression, offering candidate targets for ccRCC treatment.

The main objective is to evaluate clinical efficacy and safety of using calcipotriol–betamethasone compounding agent for psoriasis treatment through a systematic review and meta-analysis. We searched MEDLINE, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (CBM), and WanFang Data from inception till July 31, 2020. Efficacy was evaluated based on primary outcome indicators including skin lesion improvement and overall adverse reaction rate. Secondary outcome indicators included degree of life quality improvement, clinical effectiveness rate, and specific adverse reaction rates. RevMan5.3 was used to perform the meta-analysis. 22 studies finally met our inclusion criteria for the meta-analysis. The results indicated that for short-term treatment, a sequential therapy that uses calcipotriol betamethasone compounding agent and calcipotriol improves PASI score (MD = −0.94, 95% CI − 1.38 ~ − 0.49, P

Background During maturation, spermatozoa acquire motility and fertilizing capacity as they transit through the epididymis. In recent years, two-dimensional gel electrophoresis has been employed in proteomics studies conducted in rat, boar and human. However, there has not been a complete information regarding the proteins associated with sperm maturation in the epididymis. In this study, we employed iTRAQ proteomics to investigate proteins associated with sperm maturation between yak and cattleyak epididymis. Results After a successful sampling and protein extraction, the iTRAQ coupled with LC-MS/MS mass spectrometry and bioinformatics analysis were performed. We identified 288 differentially abundant proteins (DAPs) between yak and cattleyak epididymis; 151 were up-regulated while 137 were down-regulated in cattleyak relative to yak. Gene Ontology analysis identified that down-regulated DAPs in cattleyak were mostly enriched in the acetylation of protein component, along with negative and positive regulatory activities. iTRAQ proteomics data showed that the top up-regulated DAPs were mainly enriched in cell communication, cell adhesion, cytoskeleton organization, stress response, post-translational modifications and metabolic functions while the down-regulated DAPs were predominantly associated with sperm maturation, long-term sperm storage, sperm forward motility, sperm-oocyte fusion and regulatory functions. Conclusion These results provide insight into the molecular mechanisms underlying male cattleyak sterility.

Fat metabolism is a complex process regulated by a number of factors. Adiponectin receptor 1 (ADIPOR1) gene takes active part in lipid metabolism. Although, there have been some researches indicating that ADIPOR1 could influence the milk fat metabolism through targeting some factors, little is known about the effect of ADIPOR1 on goat milk fat metabolism. To investigate the regulatory role of ADIPOR1 on milk fat metabolism in GMECs, we analysed overexpression in the presence and absence of AdipoRon (50 μM) and examined knockdown using siRNA. Using RT-qPCR, we assessed ADIPOR1 mRNA expressions among different lactation stages in goat mammary gland and the expression of six genes that regulate milk fat metabolism in GMECs.ADIPOR1 mRNA expression level was higher during the various lactation stages, except dry-off period. Knockdown and overexpression results revealed a significant decrease and increase in mRNA expression of ADIPOR1 and genes considered: SREBF1, ACACA, FASN, SCD, ATGL, and HSL, respectively. Treatment of GMECs with AdipoRon 50 μM resulted in a significant (p 0.05) increase in the mRNA expression of all measured genes, except SREBF1.Overall, ADIPOR1 plays a central role in regulating the transcription of several genes involved in milk fat metabolism.

Introduction: Candida species have been regarded as global health threats due to their ability to cause invasive infections. It is challenging to treat Candida bloodstream infections, which are associated with high mortality levels. Monotherapy with antifungals is sometimes not effective against severe Candida infections, and combination therapy is needed in clinical practice.Areas covered: This review was undertaken based on data from a PubMed search for English language reports published before March 2021 by using the terms 'caspofungin,' 'Candida species,' 'combination therapy,' 'antifungal effect,' and 'novel antifungal agent.'Expert opinion: Combination therapy is an empirical strategy for treating refractory Candida infections. Caspofungin has been recommended to treat candidaemia. Caspofungin in combination therapy has some applications, while the efficacy of combination therapy in the treatment of refractory Candida infections needs more study, such as randomized controlled trials. In addition, novel compounds or drugs with potential antifungal activities have been examined, and some of them exhibit synergistic interactions with caspofungin. Thus, the antifungal activity of caspofungin in combination with antifungals or non-antifungals against Candida species in vitro and in clinical therapy is summarized.

Visual expertise refers to proficiency in visual recognition. It is attributed to accumulated visual experience in a specific domain and manifests in widespread neural activities that extend well beyond the visual cortex to multiple high‐level brain areas. An extensive body of studies has centered on the neural mechanisms underlying a distinctive domain of visual expertise, while few studies elucidated how visual experience modulates resting‐state whole‐brain connectivity dynamics. The current study bridged this gap by modeling the subtle alterations in interregional spontaneous connectivity patterns with a group of superior radiological interns. Functional connectivity analysis was based on functional brain segmentation, which was derived from a data‐driven clustering approach to discriminate subtle changes in connectivity dynamics. Our results showed there was radiographic visual experience accompanied with integration within brain circuits supporting visual processing and decision making, integration across brain circuits supporting high‐order functions, and segregation between high‐order and low‐order brain functions. Also, most of these alterations were significantly correlated with individual nodule identification performance. Our results implied that visual expertise is a controlled, interactive process that develops from reciprocal interactions between the visual system and multiple top‐down factors, including semantic knowledge, top‐down attentional control, and task relevance, which may enhance participants' local brain functional integration to promote their acquisition of specific visual information and modulate the activity of some regions for lower‐order visual feature processing to filter out nonrelevant visual details. The current findings may provide new ideas for understanding the central mechanism underlying the formation of visual expertise., The current study investigated whole‐brain connectivity dynamics modulated by visual expertise using functional connectivity analysis and the model of radiologists consisted of 20 trained superior intern radiologists and well‐matched normal controls. Our results showed there was radiographic visual experience accompanied with integration within brain circuits supporting visual processing and decision making, integration across brain circuits supporting high‐order functions, and segregation between high‐order and low‐order brain functions. The results implied that visual expertise may enhance subjects' local brain functional integration to promote their acquisition of specific visual information and modulate the activity of some regions for lower‐order visual feature processing to filter out non‐relevant visual details.

Cattleyaks (CY) are interspecific hybrids between cattle (Bos taurus) and yak (Bos gruniens, YK) exhibiting the same prominent adaptability and higher performances than YK. The main problem of this crossbreeding is that the males are sterile. Different series of events of spermatogenesis coordinate to regulate gene expressing, involving microRNAs (miRNAs). As non-coding ribonucleic acids (ncRNAs), miRNAs predominantly facilitate the regulation of gene expression at post-transcriptional stages and play important roles in the acquisition and maintenance of male fertility in reproduction. The function of miRNA in the male reproductive system extends from the testis into the epididymis, regulating gene expression and contributing to regional gene expression variations. RNA sequencing on biological replicates, we described differentially expressed miRNAs profiles for tissue from epididymis of YK and CY. In the present study, High-throughput sequencing analysis showed that 55 differentially expressed (DE) miRNAs were identified in the epididymis of YK and CY. Among these, 43 DE miRNAs were upregulated while the remaining 12 DE miRNAs were downregulated between epididymis of YK and CY. In addition, we identified that the top most important DE miRNAs, bta-miR-449c, bta-miR-539, bta- miR-136, bta-miR-504, bta-miR-31 and bta-miR-222 were involved in the process of sperm maturation in epididymis CY. It was identified that the bta-miR-449c and bta-miR-222 may play major roles in the process of sperm maturation, sperm quality, sperm count, sperm production and male infertility of CY. Furthermore, GO and KEGG analyses were performed to classify the functions of target genes for DE miRNAs. In addition, RT-qPCR validation of the DE miRNAs and its targeted genes revealed that putative miRNAs are involved in the male CY infertility by altering the gene expression. Present findings may not only increase our understanding of the molecular mechanisms regulated by the miRNAs in epididymis, but also provide a valuable information to understand the male infertility mechanism of CY.

Lung cancer is one of the most prevalent and lethal cancers worldwide (1). The traditional treatments include surgery, chemotherapy, radiotherapy and interventional therapy. The survival of lung cancer patients has dramatically been prolonged in recent years with the availability of targeted therapies, antiangiogenic agents and immune checkpoint inhibitors (ICIs). Meanwhile, technologies for the molecular detection of lung cancer have also advanced rapidly: the detection of single driver genes has evolved to cover combined multi-gene analysis, and whole exome sequencing (WES) has increasingly been applied in the clinical setting. In addition, life support technologies, including ventilators, artificial liver, and artificial kidney as well as extracorporeal membrane oxygenation (ECMO), have further matured, providing powerful forms of life support for patients with various acute and critical diseases. However, most clinical studies have only enrolled patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores from 0 to 1, with few patients having PS scores of 2; patients with a PS score of 3 or 4 have been typically excluded. Therefore, due to the lack of high-quality evidence, supportive care is recommended for patients with a PS score of 3 to 4 in the current guidelines. In the real-world, however, approximately 25% of lung cancer patients present with PS score of 3 or 4 (2) or attain scores between 3 and 4 during the course of treatment. Certain patients with high PS scores can benefit from individualized anti-tumor treatment plus appropriate life-support techniques. In 2017, the Lung Cancer Research Team at the First Affiliated Hospital of Guangzhou Medical College & Institute of Respiratory Diseases for the first time pioneered the concept of “advanced severe lung cancer” (3) and argued that standardized therapy for chronic obstructive pulmonary disease (COPD) plus anti-tumor therapy can improve both quality of life and prognosis in patients with lung cancer combined with COPD. The authors also found that the early detection of lung cancer driver genes and timely targeted therapy can be successful in treating patients with advanced severe lung adenocarcinoma with a PS score of 4 (4). In 2019, the concept of advanced severe lung cancer was further developed in a featured article (5) that indicated “Advanced severe lung cancer: does not refer to end-stage lung cancer but rather to stage IIIB, IIIC and IV lung cancers with a PS score of 2–4, which can result from a variety of factors related to the disease itself or anti-tumor drugs and which are highly likely to benefit from the currently available systemic anti-tumor therapies”. In recent years, with the advances in lung cancer diagnosis and treatment techniques and life support technologies, more clinical studies have enrolled patients with a PS score of 2, and some real-world studies have enrolled patients with PS scores of 3–4. Even for patients with early-stage lung cancer, studies have shown that patients with poor PS scores and co-morbidities have a reduced chance of undergoing surgery and an increased mortality rate (6); nevertheless, survival benefit may still be obtained through surgical modifications combined with individualized and multidisciplinary treatment (7). Therefore, the concept of severe lung cancer should not be limited to advanced lung cancer, but applied to all lung cancer patients. In particular, due to the increase in treatment options as well as substantially prolonged survival, the majority of patients may have a PS score between 2 and 4 for a certain period of time due to a variety of reasons. How to provide timely and reasonable treatment for these lung cancer patients has become a critically important real-world research topic. Therefore, we invited lung cancer experts at home and abroad to consider this issue, and this group has reached the following consensus.

Background and Objective: Studies on the relationship of thyroid stimulating hormone (TSH) within the reference range and thyroid autoimmunity with osteoporosis have produced conflicting results. The objective of this study was to investigate the association of thyroid function and thyroid autoimmune bodies (TPOAb and TgAb) with osteoporosis in euthyroid postmenopausal women. Methods: A total of 174 subjects were retrospectively included. Serum TSH, total T3, total T4, TPOAb, TgAb, vitamin D, calcium and bone mineral density were measured. Correlation and logistic multivariate regression analysis were performed. Results: Levels of TSH were lower in osteoporosis group (TSH: 2.03±1.08 vs 2.40±1.24 mIU/L, p=0.040) while TT3 and TT4 levels were similar between the two groups. The positive percentage of anti-TPO antibodies was higher in osteoporosis group (17.9% vs 6.7%, χ2= 5.13, p=0.024) while no significant difference was observed for anti-Tg antibodies (17.9% vs 8.9%, χ2=3.05, p=0.081). The Spearman correlation analysis showed that TSH levels were significantly correlated with lumbar spine BMD (r= 0.161, P=0.035) and femoral neck BMD (r = 0.152, P= 0.045). Logistical regression analysis revealed that low-normal TSH levels and positive TPOAb was an independent risk factor for osteoporosis (OR: 0.698, 95% CI: 0.505-0.965, p=0.030; OR: 3.961, 95% CI: 1.176-13.345, p=0.026 respectively). Conclusion: The results showed that low-normal TSH levels and anti-TPO antibodies were independently associated with the presence of osteoporosis in postmenopausal women.

The present study aimed to evaluate psychological distress and scrutinized whether family resilience plays a moderating role in the association between infertility-related stress and psychological distress among infertile females preparing for their first IVF-ET. A total of 492 infertile females completed self-reported measures including the Kessler 10 Psychological Distress Scale (K10), the fertility problem inventory (FPI), and the Family Resilience Assessment Scale (FRAS). The results showed 21 (65.2%) participants reported moderate or higher levels of psychological distress. While controlling for economic status, we found psychological distress to be positively linked to infertility-related stress (β=0.483, P

Background Outcomes derived from longitudinal self-reported health-related quality of life measures can be confounded by response shift. This study was aimed to detect response shift among patients with hypertension attending a community-based disease management program. Methods 240 consecutive consulting or follow-up patients with diagnosed hypertension were recruited. The Short Form 36-item Health Survey was self-administered at 12 community health service stations at baseline and four weeks after attending the program. The 4-step structural equation modeling approach assessed response shift. Results Data from 203 (84.6%) patients were eligible for analyses (mean age 65.9 ± 10.8 years, 46.3% female). The results showed uniform recalibration of social functioning ($${\upchi}_{\mathrm{SBdiff}}^{2}$$ χ SBdiff 2 (1) = 22.98, P $${\upchi}_{\mathrm{SBdiff}}^{2}$$ χ SBdiff 2 (1) = 8.84, P = 0.003), and bodily pain ($${\upchi}_{\mathrm{SBdiff}}^{2}$$ χ SBdiff 2 (1) = 17.41, P Conclusions Recalibration existed among patients with hypertension attending the disease management program. The interventions in the program might act as a catalyst that induced the response shift. We conclude that response shift should be considered in hypertension research with longitudinal health-related quality of life data.

Mei Zhu,1– 3,* Hongmei Wang,1,2,* Shujuan Zhou,4,* Jia Wei,2 Naiqing Ding,2 Jie Shao,2 Lixia Yu,2 Zhenqing Feng,5,6 Baorui Liu1,2 1The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu, 210008, People’s Republic of China; 2The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, 210008, People’s Republic of China; 3Department of Oncology, Xuzhou Cancer Hospital, Xuzhou, Jiangsu, 221005, People’s Republic of China; 4The Department of Radiation Oncology, Fudan University Shanghai Cancer Centre, Shanghai, 200032, People’s Republic of China; 5Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu, 211166, People’s Republic of China; 6Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenqing FengDepartment of Pathology, Nanjing Medical University, 101 Longmian Avenue, Jiangning, Nanjing, Jiangsu, 211166, People’s Republic of ChinaEmail fengzhenqing@njmu.edu.cnBaorui LiuThe Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, 321 Zhongshan Road, Nanjing, Jiangsu, 210008, People’s Republic of ChinaEmail baoruiliu@nju.edu.cnBackground: T cell-redirecting bispecific antibodies (BsAbs) are emerging as a potent cancer therapy that crosslinks tumor cells and T cells by simultaneously binding to tumor-associated antigen and CD3ϵ. However, immune inhibitory molecules can be remarkably upregulated after BsAbs treatment, leading to a suppressive tumor microenvironment and treatment resistance. This can be partially reversed by combination with immune checkpoint inhibitors. In our previous work, we successfully constructed the recombinant protein iRGD-antiCD3 and demonstrated that it promoted antitumor efficacy of transferred T cells by promoting T cell activation and infiltration.Methods: We detected the levels of both PD-1 and PD-L1 as resistance to iRGD-antiCD3 treatment. Using cord blood-derived T cells, we assessed the activation and effects of iRGD-antiCD3 combined with PD-1 as evidenced by activation markers, Th1/Th2-cytokines, and killing capability against tumor cells in vitro. Moreover, to better mimic the physiological characteristics of in vivo solid tumors, we generated 3D spheroids from target cell lines. Spheroids were stained with a Viability/Cytotoxicity Assay Kit and examined by confocal microscopy to study the in vitro antitumor effect of T cells co-administered with combination iRGD-antiCD3 and PD-1 blockade. The mouse peritoneal metastatic gastric tumor model was employed. The synergistic antitumor effect and safety profiles in vivo were evaluated by tumor and body weight of tumor-bearing mice.Results: We found that expression of both PD-1 and PD-L1 were increased as resistance to iRGD-antiCD3 treatment. We found that PD-1 blockade partially restored T cell activation as evidenced by elevated activation markers, Th1-cytokines, and killing capability against tumor cells in vitro. The combination of PD-1 blockade consistently and significantly increased cord blood-derived T cell cytotoxicity against 3D tumor spheroids. In vivo, we observed synergistic antitumor activity without obvious side effects.Conclusion: These results demonstrated that combining iRGD-antiCD3 with PD-1 blockade could further improve antitumor efficacy of T cells, and this strategy holds great potential for the treatment of solid malignancies.Keywords: cord blood-derived T cell, iRGD-antiCD3, PD-1 blockade, combination therapy

Urea-free reactive printing has gained popularity as part of cleaner production in the textile printing industry. Printing additives containing little to no nitrogen are being explored as substitutes for urea. In this study, the hygroscopicity, ability to swell fibers, and ability to solubilize reactive dyes of various additives were compared to explore the intrinsic connections between the structures and the above-mentioned properties. The hydrogen-bond interactions between the reactive dye and additives were characterized by 1H NMR and DSC. Additives with good hygroscopic, swelling, and solubilizing properties were selected for their potential application in urea-free reactive deep printing on viscose fabric. Results showed that among various kinds of additives, glycerol had the best hygroscopicity, 1,4-butanediol had the best ability to swell viscose fibers, and the amides had the best ability to solubilize reactive turquoise K-GL. Hygroscopicity was considered as the most important factor, followed by the ability to swell fibers. When the mixed ratio of glycerol and 1,4-butanediol was 5:5, the color performances of the binary nitrogen-free compound were higher than those of a commercial alternative. Its printing performances came close to those of urea, exhibiting great potential as a substitute for urea. Nitrogen-free alternatives will remarkably reduce the ammonia–nitrogen pollutants emitted into the environment by the reactive printing process.

Cattleyak (CY), is a cross breed between cattle and yak (YK), which display equal adaptability to the harsh environment as YK and much higher performances than YK. However, the CY is female fertile and male sterile. Previous studies were conducted on testes tissues to investigate the mechanism of male infertility in CY. There is no systematic research on genes, especially lncRNAs between CY and YK epididymis. In this study, Illumina Hiseq was performed to profile the epididymis transcriptome (lncRNA and mRNA) of CY and YK. In total 18859 lncRNAs were identified, from which lincRNAs 12458, antisense lncRNAs 2345, intronic lncRNAs 3101, and sense lncRNAs 955 respectively. We have identified 345 DE lncRNAs and 3008 DE mRNAs between YK and CY epididymis. Thirteen DEGs were validated by quantitative real-time PCR. Combing with DEG, 14 couples of lncRNAs and their target genes were both DE, and 6 of them including CCDC39, KCNJ16, NECTIN2, MRPL20, PSMC4, and DEFB112 show their potential infertility-related terms such as cellular motility, sperm maturation, sperm storage, cellular junction, folate metabolism, and capacitation. On the other hand, several down-regulated genes such as DEFB124, DEFB126, DEFB125, DEFB127, DEFB129, CES5A, TKDP1, CST3, RNASE9 and CD52 in CY compared to YK were involved in the immune response and sperm maturation. Therefore, comprehensive analysis for lncRNAs and their target genes may enhance our understanding of the molecular mechanisms underlying the process of sperm maturation in CY and may provide important resources for further research.

Influenza H3N8 viruses have been recovered frequently from wild bird species, including Anseriformes (primarily from migratory ducks) and Charadriiformes (primarily from shorebirds). However, little attention has been given to the transmission ability of H3N8 avian influenza viruses among mammals. Here, we study the potential human health threat and the molecular basis of mammalian transmissibility of H3N8 avian influenza viruses isolated from wild bird reservoirs. We classified eight H3N8 viruses into seven different genotypes based on genomic diversity. Six of eight H3N8 viruses isolated naturally from wild birds have acquired the ability to bind to the human-type receptor. However, the affinity for α-2,6-linked SAs was lower than that for α-2,3-linked SAs. Experiments on guinea pigs demonstrated that three viruses transmitted efficiently to direct-contact guinea pigs without prior adaptation. Notably, one virus transmitted efficiently via respiratory droplets in guinea pigs but not in ferrets. We further found that the PB1 S524G mutation conferred T222 virus airborne transmissibility between ferrets. We also determined that the 524G mutant increased viral pathogenicity slightly in mice compared with the WT (wild type). Based on these results, we elucidated the potential human health threat and molecular basis of mammalian transmissibility of H3N8 influenza viruses. We emphasized the need for continued surveillance of the H3N8 influenza viruses circulating in birds.

Hemophilia A (HA, OMIM: 306700) is an X-linked recessive bleeding disorder, caused by defects of the F8 gene which encodes the coagulation factor VIII (FVIII). F8 intron 22 and intron 1 inversion (...

BACKGROUND Tacrolimus has been used to treat various inflammatory skin diseases, but its safety for topical application on the oral mucosa is unknown. Exfoliative cheilitis (EC) is a chronic inflammatory disorder of the lips characterised by repeated scaling; it is difficult to manage. The aim of this study was to assess the efficacy and safety of tacrolimus 0.03% ointment as a topical treatment in patients with EC. METHODS In this randomised controlled clinical trial, 40 patients with EC were randomly assigned to receive either tacrolimus 0.03% ointment (experimental group, n = 20) or triamcinolone acetonide 0.1% cream (control group, n = 20) treatment for a 3-week period. Medication was administered in 3, 2 and 1 daily doses during the first, second and third weeks, respectively. The patients with complete healing were followed up for 3 months. The clinical outcomes were measured, including the scores regarding signs (scale, dryness, rhagades and swelling) and symptoms (rough, dry, pain, pruritus and burning sensation) at every visit. Blood concentrations of tacrolimus were assessed. RESULTS After the 3-week treatment, healing rates of scale in the experimental and control groups were 65% and 10%, respectively (P = .018). Improvement in all signs and two symptoms (rough, pruritus) was much greater in the experimental group (P

Background and purpose Melkersson-Rosenthal syndrome (MRS) is a rare neuro-mucocutaneous disease. In addition to the traditional clinical triad, there is also a diversity of clinical signs, and it may be related to other systemic diseases. Methods In the present study, we report a case of MRS with endocrine disorders that exhibits extraordinary therapeutic efficiency by using hydroxychloroquine (HCQ), explore whether there is an internal connection between MRS and endocrine disorders, and discuss the mechanism of the therapeutic efficiency of using HCQ. The hypothesis proposed for the first time is that MRS may essentially be a systemic granulomatous disease. Results The physical examination revealed orofacial swelling and fissured tongue. The histopathologic examination showed epithelioid granulomas. Combined with the other examination, this case was diagnosed as incomplete MRS. HCQ and local drugs were introduced. The patient achieved clinical recovery and psychological cure by the 18-week follow-up, and the 1-year follow-up found no reactivation of MRS. Moreover, the levels of cortisol and adrenocorticotropic were within normal ranges. Conclusions After the drug therapy was targeted at granuloma, not only did all of the symptoms related to MRS disappear, but the endocrine system also returned to normal. It is speculated that the endocrine disorder in this patient may be related to MRS. We further propose the first-time hypothesis that MRS may essentially be a systemic granulomatous disease. It provides a new medication method with high-level efficiency.

There has been an increasing interest and enormous applications in three-dimensional (3D) printing technology and its prosthesis, driving many orthopaedic surgeons to solve the difficult problem of bony defects and explore new ways in surgery approach. However, the most urgent problem is without an effective prosthesis and standard treatment strategy. In order to resolve these problems, this study was performed to explore the use of a 3D-printed anatomically conforming pelvic prosthesis for bony defect reconstruction following tumor resection and to describe a detailed treatment flowchart and the selection of a surgical approach. Six patients aged 48-69 years who had undergone pelvic tumor resection underwent reconstruction using 3D-printed anatomically conforming pelvic prostheses according to individualized bony defects between March 2016 and June 2018. According to the Enneking and Dunham classification, two patients with region I+II tumor involvement underwent reconstruction using the pubic tubercle-anterior superior iliac spine approach and the lateral auxiliary approach and one patient with region II+III and three patients with region I+II+III tumor involvement underwent reconstruction using the pubic tubercle-posterior superior iliac spine approach. The diagnoses were chondrosarcoma and massive osteolysis. After a mean follow-up duration of30.33±9.89months (range, 18-42), all patients were alive, without evidence of local recurrence or distant metastases. The average blood loss and blood transfusion volumes during surgery were2500.00±1461.51 ml (range, 1200-5000) and2220.00±1277.62 ml(range, 800-4080), respectively. During follow-up, the mean visual analogue scale (VAS) score decreased, and the mean Harris hip score increased. There were no signs of hip dislocation, prosthetic loosening, delayed wound healing, or periprosthetic infection. This preliminary study suggests the clinical effectiveness of 3D-printed anatomically conforming pelvic prostheses to reconstruct bony defects and provide anatomical support for pelvic organs. A new surgical approach that can be used to expose and facilitate the installation of 3D-printed prostheses and a new treatment strategy are presented. Further studies with a longer follow-up duration and larger sample size are needed to confirm these encouraging results.

Cutaneous metastasis from a primary visceral malignancy is a relatively uncommon clinical manifestation that occurs as an initial presentation in 1% to 12% of patients with internal malignancies. Additionally, cutaneous metastases are often late signs of an internal malignancy, and in very rare cases they may occur at the same time or before the primary cancer has been detected. Metastasis to the skin has a poor prognosis and is often a sign of widespread malignant tumors. In the present study, we report a 72-year-old male who presented with multiple rapidly growing subcutaneous nodules. Positron emission tomography-computed tomography (PET-CT) revealed a hypermetabolic concentration of radiotracer in the left lower lung and multiple organ metastases associated with multiple skin masses. Biopsy of one of the skin nodules and gene detection indicated metastatic adenocarcinoma consistent with a primary lung origin with a BRAF mutation. BRAF mutations are emerging therapeutic targets in non-small-cell lung cancer (NSCLC), as they are present in 2–4% of NSCLC cases. To the best of our knowledge, this is the first case report to show that BRAF-mutant lung adenocarcinoma can be associated with cutaneous metastasis. Early diagnosis and individualized treatment strategies may prolong patient survival.

Purpose High-dimensional image features that underlie COVID-19 pneumonia remain opaque. We aim to compare feature engineering and deep learning methods to gain insights into the image features that drive CT-based for COVID-19 pneumonia prediction, and uncover CT image features significant for COVID-19 pneumonia from deep learning and radiomics framework. Methods A total of 266 patients with COVID-19 and other viral pneumonia with clinical symptoms and CT signs similar to that of COVID-19 during the outbreak were retrospectively collected from three hospitals in China and the USA. All the pneumonia lesions on CT images were manually delineated by four radiologists. One hundred eighty-four patients (n = 93 COVID-19 positive; n = 91 COVID-19 negative; 24,216 pneumonia lesions from 12,001 CT image slices) from two hospitals from China served as discovery cohort for model development. Thirty-two patients (17 COVID-19 positive, 15 COVID-19 negative; 7883 pneumonia lesions from 3799 CT image slices) from a US hospital served as external validation cohort. A bi-directional adversarial network-based framework and PyRadiomics package were used to extract deep learning and radiomics features, respectively. Linear and Lasso classifiers were used to develop models predictive of COVID-19 versus non-COVID-19 viral pneumonia. Results 120-dimensional deep learning image features and 120-dimensional radiomics features were extracted. Linear and Lasso classifiers identified 32 high-dimensional deep learning image features and 4 radiomics features associated with COVID-19 pneumonia diagnosis (P 73% and specificity > 75% on external validation cohort with slight superior performance for radiomics Lasso classifier. Human expert diagnostic performance improved (increase by 16.5% and 11.6% in sensitivity and specificity, respectively) when using a combined deep learning-radiomics model. Conclusions We uncover specific deep learning and radiomics features to add insight into interpretability of machine learning algorithms and compare deep learning and radiomics models for COVID-19 pneumonia that might serve to augment human diagnostic performance.