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Purpose: We investigated the safety and preliminary efficacy of anti-PD-L1 antibody (ZKAB001) as maintenance therapy for localized patients with high-grade osteosarcoma to reduce the risk of recurrence and metastasis., Patients and Methods: This open-label Phase I/II study was divided into dose-escalation Phase I and expansion Phase II. Phase I used a 3+3 design with ZKAB001 at three escalating doses ranging: 5, 10, 15 mg/kg every 2 weeks in 9 patients with localized high-grade osteosarcoma and Phase II tested 10 mg/kg in 12 patients for up to 24 cycles. Primary endpoints were safety and tolerability assessed using CTCAE4.0.3., Results: Between October 2018 and 2019, 21 eligible patients were enrolled and accepted ZKAB001 treatment: 9 in the dose-escalation phase, and 12 in expansion phase. Six patients with disease progression withdrew from this study and follow-up is ongoing. The MTD was not defined in Phase I. All doses had a manageable safety profile. The recommended dose in Phase II was set at 10 mg/kg. Most frequent immune-related adverse events were thyroiditis (76.2%) and dermatitis (42.9%). Only 1 (4.8%) of 21 patients had a Grade 3 skin rash. The median 3-year event-free survival (EFS) and overall survival (OS) were not established; however, 24-month EFS was 71.4% (95% confidence interval, 47.2-86.0) and 2-year OS was 100%. Preliminary efficacy data showed EFS benefits in patients with PD-L1 positive or an MSI-H sub-population., Conclusions: Switching to maintenance using ZKAB001 showed an acceptable safety profile and provided preliminary evidence of clinical activity in localized patients with osteosarcoma., (©2022 American Association for Cancer Research.)

Standard treatment has not been established for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after discontinuation of covalent Bruton tyrosine kinase inhibitor (cBTKi) therapy. This retrospective, administrative database (Medical Data Vision) study described the patient characteristics, treatment patterns, and factors associated with receiving post-first-cBTKi treatment in Japanese patients with CLL/SLL. Patients aged ≥18 years with confirmed CLL/SLL diagnosis and treated with anti-neoplastic drugs indicated for CLL/SLL between March 2013 and February 2022 were included. Patient characteristics at baseline (first line), first cBTKi exposure (first-cBTKi), post-first-cBTKi treatment received, and the treatment sequence of CLL drugs received first line through third line, were described. Time-to-event analyses used the Kaplan-Meier method. Multivariable logistic regression analysis was used to explore factors associated with receiving post-first-cBTKi treatment among patients who discontinued first-cBTKi treatment. Among 2,424 eligible patients (median age: 72.0 years, 61.9% male), 450 (18.6%) received cBTKi in any treatment line. Among patients treated with cBTKi, 273 (60.7%) discontinued treatment; 56.0% of them (n = 153/273) received subsequent treatment. Median duration of post-first-cBTKi treatment was 2.2 months (95% confidence interval [CI]: 1.8, 3.5). The most common regimens post-first-cBTKi were cBTKi therapy (47.7%), bendamustine-based therapy (17.0%), and venetoclax-based therapy (13.1%). Patients aged <75 years (odds ratio [OR] [95% CI]: 2.0 [1.2, 3.4]) and those who did not receive blood transfusion during cBTKi treatment (OR [95% CI]: 2.3 [1.3, 4.1]) were more likely to receive post-first-cBTKi treatment. In conclusion, Japanese patients with CLL/SLL received various treatments for short duration after first-cBTKi discontinuation.

Difficulties with social aspects of language are among the hallmarks of autism spectrum disorder (ASD). These communication differences are thought to contribute to the challenges that adults with ASD experience when seeking employment, underscoring the need for interventions that focus on improving areas of weakness in pragmatic and social language. In this paper, we describe a transformer-based framework for identifying linguistic features associated with social aspects of communication using a corpus of conversations between adults with and without ASD and neurotypical conversational partners produced while engaging in collaborative tasks. While our framework yields strong accuracy overall, performance is significantly worse for the language of participants with ASD, suggesting that they use a more diverse set of strategies for some social linguistic functions. These results, while showing promise for the development of automated language analysis tools to support targeted language interventions for ASD, also reveal weaknesses in the ability of large contextualized language models to model neuroatypical language.

Human cytomegalovirus (HCMV) is a ubiquitous pathogen belongs to betaherpesvirus subfamily. RNA2.7 is a highly conserved long non-coding RNA accounting for more than 20% of total viral transcripts. In our study, functions of HCMV RNA2.7 were investigated by comparison of host cellular transcriptomes between cells infected with HCMV clinical strain and RNA2.7 deleted mutant. It was demonstrated that RNA polymerase II (Pol II)-dependent host gene transcriptions were significantly activated when RNA2.7 was removed during infection. A 145 ​nt-in-length motif within RNA2.7 was identified to inhibit the phosphorylation of Pol II Serine-2 (Pol II S2) by reducing the interaction between Pol II and phosphorylated cyclin-dependent kinase 9 (pCDK9). Due to the loss of Pol II S2 phosphorylation, cellular DNA pre-replication complex (pre-RC) factors, including Cdt1 and Cdc6, were significantly decreased, which prevented more cells from entering into S phase and facilitated viral DNA replication. Our results provide new insights of HCMV RNA2.7 functions in regulation of host cellular transcription., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2022 The Authors. Publishing services by Elsevier B.V. All rights reserved.)

58 cases of metastatic sarcoma were reviewed retrospectively in order to compare the efficacy and safety of concurrent (n=24, group A) versus sequential (n=34, group B) use of chemotherapy and targeted therapy in metastatic sarcoma. Progression-free survival (PFS) 1 was defined as the duration between initiation of first-line treatment to disease progression or recurrence. PFS' was defined as the duration between initiation of first-line treatment to the failure of chemotherapy and targeted therapy, and overall survival (OS) was defined as the duration between initiation of first-line treatment to the date of last follow-up or death. The results revealed that patients in group A possessed a higher tumor burden compared to those in group B (P=0.049). Survival curves revealed that the median PFS1 (15.2 vs. 5.4 months, P=0.000), median PFS' (15.2 vs. 10.8 months, P=0.049), and median OS (42.3 vs. 25.3 months, P=0.041) of subjects in group A were remarkably longer than those of group B. Subgroup analysis showed that patients in group A experienced more favorable PFS1 (15.2 vs. 3 months, P=0.000), PFS' (15.2 vs. 5.8 months, P=0.003), and OS (35.2 vs. 15.7 months, P=0.011) than those in group B, with findings especially prominent in patients with tumor burden ≥ 10 cm in comparison to patients with tumor burden < 10 cm (P ≥ 0.05). All grades of leukopenia, thrombocytopenia, fatigue, and oral mucositis were more frequently diagnosed in patients of group A compared to those of group B. However, there were no significant differences between the rates of Grade 3-4 adverse events between the two groups. This investigation suggests that the concurrent use of targeted therapy and chemotherapy may be useful and safe as a first-line treatment in patients with metastatic sarcoma who possess a high tumor burden., Competing Interests: None., (AJTR Copyright © 2021.)

Human cytomegalovirus (HCMV) is a double-strand DNA virus widely infected in human. Circular RNAs (circRNAs) are non-coding RNAs with most functions of which keep unknown, and the effects of HCMV productive infection on host circRNA transcriptions remain unclear. In this study, we profiled 283 host circRNAs that significantly altered by HCMV productive infection in human embryonic lung fibroblasts (HELF) by RNA deep sequencing and bioinformatics analysis. Among these, circSP100, circMAP3K1, circPLEKHM1, and circTRIO were validated for their transcriptions and sequences. Furthermore, characteristics of circSP100 were investigated by RT-qPCR and northern blot. It was implied that circSP100 was produced from the sense strand of the SP100 gene containing six exons. Kinetics of circSP100 and SP100 mRNA were significantly different after infection: circSP100 levels increased gradually along with infection, whereas SP100 mRNA levels increased in the beginning and dropped at 24 h post-infection (hpi). Meanwhile, a total number of 257 proteins, including 10 HCMV encoding proteins, were identified potentially binding to cytoplasmic circSP100 by RNA antisense purification (RAP) and mass spectrometry. Enrichment analysis showed these proteins were mainly involved in the spliceosome, protein processing, ribosome, and phagosome pathways, suggesting multiple functions of circSP100 during HCMV infection.

Osteosarcoma is the most frequent primary bone tumor with poor prognosis. Through RNA-sequencing of 100,987 individual cells from 7 primary, 2 recurrent, and 2 lung metastatic osteosarcoma lesions, 11 major cell clusters are identified based on unbiased clustering of gene expression profiles and canonical markers. The transcriptomic properties, regulators and dynamics of osteosarcoma malignant cells together with their tumor microenvironment particularly stromal and immune cells are characterized. The transdifferentiation of malignant osteoblastic cells from malignant chondroblastic cells is revealed by analyses of inferred copy-number variation and trajectory. A proinflammatory FABP4 + macrophages infiltration is noticed in lung metastatic osteosarcoma lesions. Lower osteoclasts infiltration is observed in chondroblastic, recurrent and lung metastatic osteosarcoma lesions compared to primary osteoblastic osteosarcoma lesions. Importantly, TIGIT blockade enhances the cytotoxicity effects of the primary CD3 + T cells with high proportion of TIGIT + cells against osteosarcoma. These results present a single-cell atlas, explore intratumor heterogeneity, and provide potential therapeutic targets for osteosarcoma.

Objective: To quantify the expression of miR-195 and miR-497 in acute stroke and to evaluate their correlations with post-stroke cognitive impairment., Methods: A total of 108 patients with acute stroke admitted to our hospital from January, 2019 to June, 2020 were enrolled as a patient group, and 76 healthy volunteers were recruited as a normal group. Levels of serum miR-195 and miR-497 in the two groups were quantified. Neurological and cognitive functions were tested by National Institutes of Health Stroke Scale (NIHSS) and Montreal Cognitive Assessment (MoCA), respectively. Diagnostic value of serum miR-195 and miR-497 in acute stroke was evaluated by receiver operating characteristic (ROC) curve, and independent risk factors were determined by multivariate logistic regression., Results: Levels of serum miR-195 and miR-497 increased in acute stroke. The area under the curve (AUC) of serum miR-195 in the diagnosis of acute stroke was 0.901, while that of serum miR-497 was 0.922. Levels of miR-195 and miR-497 were positively correlated with NIHSS score and negatively correlated with MoCA score. Logistic regression analysis demonstrated that family history of stroke, diabetes, hypertension, NIHSS score, MoCA score, miR-195, and miR-497 were independent risk factors for acute stroke., Conclusion: Serum miR-195 and miR-497 are elevated in acute stroke and associated with the loss of neurologic and cognitive functions. They may be biomarkers for diagnosis and prognosis of acute stroke., Competing Interests: None., (IJCEP Copyright © 2020.)

Osteosarcoma (OS) is the most common primary bone malignancy with high rates of recurrence and metastasis. OS often spreads to lungs, an optimized model for studying lung metastatic OS cells may help develop potential therapies for patients with lung metastasis. Here we firstly report an organoid culture system for lung metastatic OS tissues. We provided a fully described formula that was required for establishing lung metastatic OS organoids (OSOs). Using this protocol, the lung OSOs were able to be maintained and serially propagated for at least six months; the OSOs can also be generated from cryopreserved patient samples without damaging the morphology. The patient-derived lung OSOs retained the cellular morphology and expression of OS markers (Vimentin and Sox9) that recapitulate the histological features of the human OS. The microenvironment of primary lung metastatic OSOs preserved a similar T cell distribution with the human lung OS lesions; this provided a possible condition to explore how OS cells may react to immunotherapy. OSOs established from this protocol can be further utilized for studying various aspects of OS biology (e.g., tumorigenesis and drug screen/discovery) for precision medicine.

Background: Circular RNA (circRNA) is highly expressed in the brain tissue, but its molecular mechanism in cerebral ischemia-reperfusion remains unclear. Here, we explored the role and underlying mechanisms of circRNA antisense non-coding RNA in the INK4 locus (circ&#95;ANRIL) in oxygen-glucose deprivation and reoxygenation (OGD/R)-induced cell injury., Results: The expression of circ&#95;ANRIL in OGD/R-induced human brain microvascular endothelial cells (HBMECs) was significantly up-regulated, while that of miR-622 was significantly down-regulated. Overexpression of circ&#95;ANRIL significantly inhibited the proliferation of OGD/R-induced HBMECs and aggravated OGD/R-induced cell apoptosis. Moreover, circ&#95;ANRIL overexpression further increased the secretion of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 in OGD/R-treated HBMECs. The results of bioinformatics analysis and luciferase reporter assay indicated that circ&#95;ANRIL served as an miR-622 sponge to negatively regulate the expression of miR-622 in OGD/R-treated HBMECs. Additionally, circ&#95;ANRIL silencing exerted anti-apoptotic and anti-inflammatory effects by positively regulating the expression of miR-622. Furthermore, inhibition of OGD/R-induced activation of the nuclear factor (NF)-κB pathway by circ&#95;ANRIL silencing was significantly reversed by treatment with miR-622 inhibitor., Conclusions: Knockdown of circ&#95;ANRIL improved OGD/R-induced cell damage, apoptosis, and inflammatory responses by inhibiting the NF-κB pathway through sponging miR-622.

Up to now, the UL16-17 region of human cytomegalovirus (HCMV) has not been well characterized at the level of mRNA and protein, especially for the Han strain, the first clinical HCMV strain in China. In previous studies, three transcripts were detected from the UL16-17 region by northern blot analysis for Merlin strain. Transcriptions of UL16 and UL17 were also studied by 5' rapid amplification of cDNA ends (5'RACE) and deep sequencing for AD169 and Towne strains, respectively. However, details of 3' end of UL16 and UL17 transcripts have never been confirmed by 3'RACE. The expressing phage of the UL16-17 region needs further research by northern blot, too. In the present study, cDNA library screening, northern blot and RACE were used to identify the transcription characteristics of the UL16-17 region. Mainly, 3 clusters of transcripts with the same 3' end were found to be expressed from the UL16-17 region in both Han and AD169 strains. The lengths of the core transcripts among the 3 clusters were 1,254nt, 718nt and 468nt, respectively. The corresponding 5' ends are at nt23119, nt23655, nt23905 in the HCMV Han genome. The consistent 3' end is located at nt24372 in the Han genome. The 1,254nt and 468nt transcripts are transcribed in early and late phases, and the 718nt transcript is transcribed only in the late phase.

Human cytomegalovirus (HCMV)-encoded microRNAs (miRNAs) are involved in posttranscriptional regulation of gene expression. Extracellular vesicles (EVs) can incorporate miRNAs. Relationship between HCMV infection and miRNAs in EVs remains unknown. EVs were isolated from supernatants of human embryonic lung fibroblasts (HELF) cells. Profiles of miRNAs in EVs were analyzed by deep sequencing. Dynamics of candidate viral miRNAs transportation via EVs was investigated using TaqMan PCR. Levels of candidate viral miRNAs in serum EVs from infants with HCMV active infection were detected and analyzed with their clinical index levels. A total of 16 HCMV miRNAs were found in EVs from infected HELF. Levels of miR-US25-1-5p and miR-UL112-3p in EVs increased at 6 h post-infection and were correlated with those in cells (for miR-US25-1-5p: r 2  = 0.9375, p value < 0.05; for miR-UL112-3p: r 2  = 0.7557, p value < 0.05). Viral miRNAs were transported into recipient cells at 2 h post-incubation. Moreover, levels of miR-US25-1-5p in serum EVs showed positive correlations with serum levels of γ-glutamyl transpeptidase, direct bilirubin, and total bile acid. Levels of miR-UL112-3p in serum EVs showed a positive correlation with serum levels of direct bilirubin. HCMV miRNAs could be transported to uninfected cells via EVs. Levels of miR-US25-1-5p and miR-UL112-3p in serum EVs from infants with HCMV active infection were significantly correlated with liver damage.

Background: Our previous study found that consumption of very low mineral drinking water may retard height development in schoolchildren; however, its association with bone modeling remained unknown., Objectives: The aim of this study was to investigate the influence of very low mineral water on biomarkers of bone modeling in children., Methods: A retrospective cohort study was conducted among 2 groups of 10-13-y-old children who had consumed drinking water with normal mineral contents (conductivity 345 μs/cm, the NW group including 119 boys and 110 girls) or very low mineral contents (conductivity 40.0 μs/cm, the VLW group including 223 boys and 208 girls) in school for 4 y. Differences in daily total mineral intakes, developmental parameters, serum biomarkers of osteoblast activity, and bone formation and resorption between the 2 groups were analyzed with independent t test and chi-square test. Associations of developmental parameters and serum biomarkers with Ca intake from drinking water were analyzed with multiple linear regression and binary logistic regression., Results: Compared with the NW group, the VLW group had lower daily Ca intake, height increase, bone mineral content (BMC), osteoblast activity [serum bone alkaline phosphatase (BALP)] (means ± SDs: 433 ± 131 mg, 16.6 ± 8.27 cm, 1.92 ± 0.431 kg, and 9.28 ± 1.42 μg/L compared with 497 ± 155 mg, 22.3 ± 8.45 cm, 2.14 ± 0.354 kg, and 11.0 ± 0.823 μg/L, respectively, P < 0.001), and higher bone resorption [serum crosslinked C-telopeptide of type I collagen (CTX), mean ± SD: 142 ± 46.9 nmol/L compared with 130 ± 40.6 nmol/L, P = 0.001). Ca intake from drinking water was positively associated with height increase, BMC, and BALP (β: 0.0667, 95% CI: 0.0540, 0.0793; β: 3.22, 95% CI: 2.37, 4.08; and β: 23.9, 95% CI: 20.6, 27.2), respectively, P < 0.001), and was negatively associated with CTX (β: -0.206, 95% CI:-0.321, -0.0904, P < 0.001)., Conclusions: These changes suggested that consumption of very low mineral water may be associated with osteoblast inhibition, bone resorption activation, bone mineral reduction, and height development retardation. The health risk of consuming very low mineral water should be considered in children., (Copyright © American Society for Nutrition 2019.)

To determine the function of miR-206 in epilepsy. Epileptic rat model was established by intra-amygdala injection of kainic acid (KA). Expression levels of miR-206, C-C Motif Chemokine Ligand 2 (CCL2) and interleukin-1β (Il-1β) in hippocampus tissues was measured by reverse transcription-quantitative PCR (RT-qPCR) and western blot. Dual luciferase reporter assay was performed to determine the binding of miR-206 to 3' untranslated region (UTR) of CCL2. Finally, brain waves were recorded and Hematoxylin and eosin (HE) staining and Nissl's staining were performed on the epileptic rat injected with LPS, miR-206 agomir, adeno-associated virus (AAV) expressed CCL2 alone or in combination. Expression of miR-206 was specially decreased in hippocampus tissues compared to cortex in response to KA induced pathologic brain activity. Enforced expression of miR-206 by injection miR-206 agomir not only decreased seizure activity, but also protected KA-induced neuronal loss. And enforced expression of miR-206 suppressed increase of C-C Motif Chemokine Ligand 2 (CCL2) and interleukin-1β (Il-1β) which were induced by injection of KA or KA combined with lipopolysaccharide (LPS). Further more, results of dual luciferase reporter assay confirmed CCL2 was a target of miR-206. Finally, co-injection adeno-associated virus (AAV) expressed CCL2 with miR-206 agomir abolished the function of miR-206 agomir. Taken together, our results showed that expression of miR-206 could inhibit seizure-induced brain injury by targeting CCL2. Our results showed that expression of miR-206 could inhibit seizure-induced brain injury by targeting CCL2.

Objectives: Neuropathic pain (NP) is one of the main challenges towards NP syndrome treatment. miR-340-5p exhibit different expression levels in NP models. Its effects on NP remained unclear. The objective of this study was to explore the potential regulation mechanisms of miR-340-5p in NP., Methods: Rat model of chronic constriction injury (CCI) was established to induce NP in vivo. NP levels were assessed using mechanical withdrawal threshold (MWT). The inflammation response in CCI rats were determined by HE staining and ELISA assay. The target genes of miR-340-5p were verified by luciferase report assays., Results: In CCI rats, level of miR-340-5p was down-regulated both in spinal cord tissues and isolated microglial cells. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were decreased in CCI rats, which were restored upon miR-340-5p overexpression. miR-340-5p overexpression also decreased inflammation as well as expression levels of COX-2, IL-1β, TNF-α and IL-6 in CCI rats. Luciferase report assays revealed Rap1A was a target gene of miR-340-5p in the experimental model. Elevated miR-340-5p decreased Rap1A expression level in vitro and in vivo. Overexpression of Rap1A protein restored expression levels of COX-2, IL-1β, TNF-α and IL-6, reduced the PWT and PWL and increased inflammation response in CCI rats., Conclusion: miR-340-5p alleviated CCI-induced NP by targeting Rap1A. miR-340-5p and Rap1A may be the potential treatment targets for NP therapeutics.

To investigate the correlation between the air phthalate acid ester (PAE) exposure and serum PAE concentration and the effects of PAE exposure on reproductive health among Chongqing traffic-patrol policemen. In 2013, 32 traffic-patrol policemen working in an area with poor air quality in Chongqing and 28 traffic-patrol policemen working in an area with good air quality were selected. Their blood levels of 14 PAEs and six reproductive hormones were determined. Air samples were collected from four traffic-patrol platforms. The concentrations of 14 PAEs in the air samples were evaluated. All 14 PAEs were detected in the blood samples. The concentrations of seven PAEs in the total suspended particulate, namely, dimethyl phthalate, diethyl phthalate, dibutyl phthalate, bis (2-ethox-yethyl) phthalate, dihexyl phthalate, benzyl butyl phthalate, and bis (2-n-butoxyethyl) phthalate, were positively and significantly associated with the blood levels of these PAEs in the participants. All the sex hormone levels measured here were significantly different between the participants from the two areas. The PAE concentrations in the blood samples were correlated with the reproductive hormone levels in the participants. Air PAE pollution may be a major source of PAE exposure in the traffic-patrol policemen of Chongqing.

The optimal first-line treatment for primary Ewing sarcoma (ES) of the spine is unclear, especially when the patients present with acute neurological deficits. This study aimed to retrospectively analyze the effect of first-line treatment with surgery or chemotherapy on neurological and survival outcomes of ES of the spine. 39 patients treated between January 2005 and December 2016 were included in the present analysis. 29 (74.4%) presented with symptomatic spinal cord compression at diagnosis. 21 patients were submitted to primary surgery followed by chemotherapy and local radiotherapy, while 18 patients received induction chemotherapy before surgery and/or local radiotherapy. Neurological deficit before and after treatment, event-free survival and overall survival were analyzed. The results indicated that chemotherapy as the first-line treatment could achieve similar results as primary surgery in preserving neurological function, even in case of major neurological deficits. Compared with primary surgery, induction chemotherapy contributed to a higher rate of en bloc resection with a microscopic negative margin (R0) of primary tumor (72.7% vs. 28.6%, P < 0.05). Multivariate Cox regression analyses revealed that initial chemotherapy was a favorable independent prognostic factor of event-free survival (hazard ratio, 0.215; 95% confidence interval, 0.077-0.596; P = 0.003) and overall survival (hazard ratio, 0.288, 95% confidence interval, 0.098-0.852; P = 0.024). In conclusion, our study suggests that first-line treatment of ES of the spine should be induction chemotherapy, even in case of major neurological deficits., Competing Interests: None.

Viruses commonly create favorable cellular conditions for their survival through multiple mechanisms. MicroRNAs (miRNAs), which function as post-transcriptional regulators, are utilized by human cytomegalovirus (HCMV) in its infection and pathogenesis. In the present study, the DNA replication inhibitor Geminin (GMNN) was identified to be a direct target of hcmv-miR-US5-1. Overexpression of hcmv-miR-US5-1 could block the accumulation of GMNN during HCMV infection, and the decrease of GMNN expression caused by hcmv-miR-US5-1 or GMNN specific siRNA reduced HCMV DNA copies in U373 cells. Meanwhile, ectopic expression of hcmv-miR-US5-1 and consequent lower expression of GMNN influenced host cell cycle and proliferation. These results imply that hcmv-miR-US5-1 may affect viral replication and host cellular environment by regulating expression kinetics of GMNN during HCMV infection.

Objective: To investigate the effect of the traditional Chinese medicine compound Yisui Lixue decoction on apoptosis of marrow cells in rats with myelodysplastic syndrome (MDS) induced by dimethyl benzanthracene (DMBA). 
 Methods: The rats with MDS induced by the chemical mutagens DMBA were divided into 5 groups (12 rats in each group): a control group, a model+PBS group, a model+compound Zaofan pill group, a model+low dose of Yisui Lixue decoction group and a model+high dose of Yisui Lixue decoction group. After DMBA treatment for 14 days, rats were treated with different drugs for 1 month and executed on the 31 day. The peripheral blood cells, expressions of B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax), apoptosis of bone marrow cells were measured.
 Results: The counts of peripheral leukocyte, erythrocyte, hemoglobin and platelet in the model+PBS group were significantly decreased compared with those in the control group (P<0.01), while the peripheral hemograms of the treatment groups were improved significantly compared with those in the model+PBS group (P<0.05 or P<0.01), especially in the model+high dose group (P<0.01). In the model+PBS group, the expressions of Bax and Bcl-2 was significantly increased (P<0.01) or decreased (P<0.01), respectively, which were reversed by treatment of Yisui Lixue decoction (P<0.05 or P<0.01), especially in the model+high dose group (P<0.01). Compared with control group, the total apoptosis rate, earlier apoptosis and later apoptosis rate of bone marrow cells in the model+PBS group were increased (P<0.01), which were blocked by treatment of Yisui Lixue decoction (P<0.05 or P<0.01), and the model+high dose group was better than the model+low dose group. 
 Conclusion: The traditional Chinese medicine compound Yisui Lixue decoction can improve peripheral hemogram, decrease the expression of Bax, increase the expression of Bcl-2, and reduce the apoptosis of bone marrow cells.

CD133 and CD44 are commonly used markers of cancer stem cells (CSCs), which are characterized by their ability for self-renewal and tumorigenicity. However, the clinical value and significance of CD133 and CD44 in lung metastasis of osteosarcoma (OS) remains controversial. The purpose of this study was to investigate whether CD133(+) CD44(+) cells mediates the metastasis of OS. We identified the CD133(+) CD44(+) cells in lung metastatic lesions and OS cell lines, and next demonstrated CD133(+) CD44(+) cells were more aggressive in sphere formation, migration and invasiveness compared with CD133(+) CD44(-) , CD133(-) CD44(+) , or CD133(-) CD44(-) cells. We finally sorted the CD133(+) CD44(+) and CD133(-) CD44(-) cells from Saos-2 cell lines, after intratibial xenograft in nude mice, these cells developed primary tumors, and CD133(+) CD44(+) cells are more potential to form lung metastatic tumors. Thus we concluded that CD133(+) CD44(+) cells may mediate in the lung metastasis of OS., (© 2015 Wiley Periodicals, Inc.)

Human cytomegalovirus (HCMV) infection can cause severe illness in immunocompromised and immunodeficient individuals. As a novel HCMV‑encoded major histocompatibility complex class I‑related molecule, the UL142‑encoded protein (pUL142) is capable of suppressing natural killer (NK) cell recognition in the course of infection. However, no host factors that directly interact with HCMV pUL142 have been reported so far. In order to understand the interactions between HCMV pUL142 and host proteins, the current study used yeast two‑hybrid screening, a GST pull‑down assay and an immunofluorescence assay. A host protein, the SNARE‑associated protein Snapin, was identified to directly interact and colocalize with HCMV pUL142 in transfected human embryonic kidney‑293 cells. Snapin is abundantly expressed in the majority of cells and mediates the release of neurotransmitters through vesicular transport in the nervous system and vesicle fusion in non‑neuronal cells. It is hypothesized that HCMV pUL142 may have an impact on the neurotransmitter release process and viral dissemination via interaction with Snapin.

In a previous study, one spliced transcript of human cytomegalovirus (HCMV), named UL21.5 was identified. UL21.5 has been found to be one of the viral transcripts packaged within HCMV particles. The UL21.5 mRNA is translated into a secreted glycoprotein, which is a viral chemokine decoy receptor specifically interacting with regulated upon activation normal T cell expressed and secreted (RANTES). In the present study, four novel low-abundance 3'-coterminal spliced transcripts were identified to be transcribed from the UL21.5 gene region of a low-passage HCMV strain during the late infection phase by cDNA library screening, northern blot hybridization, reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE)-PCR. Three splicing donor and three splicing acceptor sites found in the UL21.5 gene region were validated to be functional in an in vitro expression system. In addition, the determinant regulatory region that is necessary for the splice donor site at nucleotide (nt) 25533 was located in a 9-bp sequence around the site; the regulatory regions for the splice acceptor sites at nt 26597 and nt 26633 were located in a 20-bp sequence upstream of the site at nt 26597 and in a 10-bp sequence from nt 26641 to nt 26650 downstream of the site at nt 26633, respectively.

Fear could be acquired indirectly via social observation. However, it remains unclear which cortical substrate activities are involved in vicarious fear transmission. The present study was to examine empathy-related processes during fear learning by-proxy and to examine the activation of prefrontal cortex by using functional near-infrared spectroscopy. We simultaneously measured participants' hemodynamic responses and skin conductance responses when they were exposed to a movie. In this movie, a demonstrator (i.e., another human being) was receiving a classical fear conditioning. A neutral colored square paired with shocks (CS(shock)) and another colored square paired with no shocks (CS(no-shock)) were randomly presented in front of the demonstrator. Results showed that increased concentration of oxygenated hemoglobin in left prefrontal cortex was observed when participants watched a demonstrator seeing CS(shock) compared with that exposed to CS(no-shock). In addition, enhanced skin conductance responses showing a demonstrator's aversive experience during learning object-fear association were observed. The present study suggests that left prefrontal cortex, which may reflect speculation of others' mental state, is associated with social fear transmission.