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Paraquat (PQ) is a heterocyclic pesticide that not only damages the testicular development and reduces the quality of semen, but also disturbs the secretion of hormones in the reproductive system. However, the effects of PQ on oocyte maturation and its toxic mechanism have not been yet fully clarified. Here we showed that PQ exposure could have toxic effects on porcine oocyte maturation. PQ exposure with 100 μM inhibited cumulus cell expansion and significantly reduced the rate of first polar body extrusion during oocyte maturation. PQ-exposed oocytes could not develop to the 2-cell and blastocyst stage. PQ exposure with 100 μM significantly increased abnormal spindle rate (65.2% ± 1.0%) and misaligned chromosome rate (63.2% ± 3.4%) compared to the control group (38.3% ± 1.0% and 38.4% ± 1.0%, respectively; P 0.05). F-actin also exhibited reduced distribution in PQ-exposed oocytes (10.3% ± 1.0%) compared to the control group (14.4% ± 1.0%, P 0.05). In addition, PQ exposure reduced the active mitochondria levels, but apparently increased the reactive oxygen species (ROS), rH2AX, and LC3 (autophagy marker) levels. qPCR analyses showed that PQ exposure caused the aberrant expression of genes associated with cumulus cell expansion, but did not affect the expression of apoptosis-related genes. Taken together, these results indicate that PQ exposure impaired oocyte nuclear and cytoplasmic maturation probably through oxidative stress.

BACKGROUND Spinal extradural arachnoid cysts (SEACs) are a rare cause of spinal cord compression. Typically, these cysts communicate with the intradural subarachnoid space through a small defect in the dural sac. For symptomatic SEACs, the standard treatment is to remove the cyst in total with a (hemi)laminectomy or laminoplasty. We present a rare case of bi-segmental non-communicating SEACs and describe our experience of using an endoscopic minimal access technique to remove bi-segmental non-communicating SEACs. CASE SUMMARY A 79-year-old female presented with pain related to bi-segmental SEACs at the T11-L1 segments. She underwent sequential transforaminal percutaneous endoscopic thoracic cystectomy of the SEACs. Following her first procedure, spinal magnetic resonance imaging demonstrated complete excision of the cyst at the T12-L1 segment. However, the cyst at the T11-T12 segment was still present. Thus, a second procedure was performed to remove this lesion. The patient’s right-sided lumbar and abdominal pain improved significantly postoperatively. Her Japanese Orthopaedic Association score increased from 11 to 25, her visual analogue scale score was reduced from 8 to 1. The physical and mental component summary of the 36-item short-form health survey (SF-36) were 15.5 and 34.375 preoperatively, and had increased to 79.75 and 77.275 at the last follow-up visit, respectively. CONCLUSION Bi-segmental non-communicating SEACs are extremely rare. Endoscopic surgery is a safe, effective, and reliable method for treating these cysts. In the event of bi-segmental SEACs, it is important to identify whether both cysts are communicating before surgery, and if not, to remove both cysts separately during the index surgery to avoid re-operation.

Abnormal vascular smooth muscle cell (VSMC) proliferation has an important role in the pathogenesis of both atherosclerosis restenosis and hypertension. Vascular endothelial growth factor (VEGF) has been shown to stimulate VSMC proliferation. In addition, angiogenesis is one of the hallmarks of cancerous growth. VEGF is the key modulator for the initial stages of angiogenesis that acts through the endothelial-specific receptor tyrosine kinases (VEGFRs). VEGFR-2 blockage is a good approach for suppression of angiogenesis. In order to discover novel VEGFR-2 TK inhibitors, we have designed and synthesized three new series of pyridine-containing compounds. The new compounds were all screened against a panel of three cell lines (HepG-2, HCT-116, and MCF-7). Promising results encouraged us to additionally evaluate the most active members for their in vitro VEGFR-2 inhibitory effect. Compound 7a, which is the most potent candidate, revealed a significant increase in caspase-3 level by 7.80-fold when compared to the control. In addition, Bax and Bcl-2 concentration levels showed an increase in the proapoptotic protein Bax (261.4 Pg/ml) and a decrease of the antiapoptotic protein Bcl-2 (1.25 Pg/ml) compared to the untreated cells. Furthermore, compound 7a arrested the cell cycle in the G2/M phase with induction of apoptosis. The immunomodulatory effect of compound 7a, the most active member, showed a reduction in TNF-α by 87%. Also, compound 7a caused a potent inhibitory effect on smooth muscle proliferation. Docking studies were also performed to get better insights into the possible binding mode of the target compounds with VEGFR-2 active sites.

Background The aim of this study was to summarize the clinical characteristics, therapeutic effects and prognosis of patients with rhabdomyosarcoma (RMS) and bone marrow metastasis, improve the understanding of this disease. Method This was a single-institution retrospective study involving the children with RMS, who presented with bone marrow metastasis at initial presentation to our hospital between 1st, Jan, 2006 and 31st, Dec,2019. Follow-up concluded on 31st, Dec, 2020 and the clinical data were collected and analysed. Result Between 1st Jan 2006 and 31st Dec 2019, 13 eligible patients presented to our hospital, including 10 males and 3 females, these eligible patients accounted for 4.5% of all RMS patients. The median age at onset was 5.6 years (range 1.7-14 years). The patients not only had unfavourable primary sites, but also had multiple metastases. The bone marrow aspirate samples of the patients comprised 8-95% blast-like cells. Nine of 13 patients were misdiagnosed with haematological malignancies or other solid tumours. With respect to histology, four of 13 children were classified as embryonal RMS and nine as alveolar RMS. Eleven patients underwent PAX-FOXO1 fusion testing; eight had the POX- FOXO1 fusion gene. Immunohistochemically(IHC) analysis revealed that the tumour cells were positive for Desmin, Vimentin, Myo-D1 and Myogenin. More importantly, the patients had extremely poor prognoses, the median EFS was 12.0 months (range 3-28.3 months) and the median OS was 27.0 months (range6-46.2 months). Conclusion This study demonstrates that children with RMS and bone marrow metastasis usually exhibit atypical primary sites and multiple metastases, with presentation mimicking haematological malignancies or other solid tumors at initial presentation. Pathology and IHC analysis combined with POX-FOXO1 fusion gene detections can effectively confirm the diagnosis. These patients are more likely to relapse or progress during early treatment and are prone to intracranial metastasis. While multidisciplinary therapy combined with Temozolomide may prevent it, further prospective research is required to evaluate the therapeutic effects.

It has been suggested that aging and inflammation play key roles in the development of delirium. In the present study, we investigated the differences of the DNAm patterns in the TNF gene between patients with delirium and without. The data and samples derived from previous and ongoing cohort studies were analyzed. DNAm levels of the TNF gene were analyzed using the Illumina EPIC array genome-wide method and pyrosequencing method. Correlations between age and DNAm levels of each CpG were calculated. Several CpG in the TNF gene in blood showed negative correlation between their DNAm and age in delirium cases both with the EPIC array and by the pyrosequencing method. However, there was no CpG that had significant correlation between their DNAm and age regardless of delirium status among buccal samples. On the other hand, among peripheral blood mononuclear cells samples, it was found that several CpG showed negative correlation between their DNAm and age in delirium cases. The evidence of DNAm change in the TNF gene among delirious subjects was demonstrated.

BACKGROUND MRI is the most effective diagnostic tool of osteonecrosis of the femoral head (ONFH), especially for early diagnosis, but its detection of subchondral or cortical fractures is less accurate than CT. Therefore, it is difficult to accurately stage ONFH in the peri-collapse period by MRI. PURPOSE To improve the accuracy of MR for distinguishing between Association Research Circulation Osseous (ARCO) stages 2 and 3A in ONFH. STUDY TYPE Retrospective. SUBJECTS One hundred and fifty five cases of ARCO stage 2/3A of ONFH underwent MR examinations, M/F = 72/83. CT was used as reference standard for collapse, which was decided by an orthopedist and a radiologist in consultation. FIELD STRENGTH/SEQUENCE 3 T/axial and coronal T1 -weighted Turbo Spin Echo (T1 W TSE) sequence, axial T2 -weighted fat-saturated (T2 W FS) TSE sequence, and coronal proton density-weighted imaging (PDWI)-FS-Dixon fat/water image. ASSESSMENT Five potential MR signs (the maximum width of the necrotic-viable interface, bone marrow edema (BME), irregular articular surface of the femoral head, T2 heterogeneous high signal, and the absence of a necrotic-viable interface with the morphology of closed loop) were evaluated blindly by five radiologists independently and the total scores of different combinations of MR signs were calculated. STATISTICAL TESTS Mann-Whitney U test and Chi-square test were used to evaluate age, gender, and MR signs differences between the two groups. ROC curve was used to access the distinguishing value of MR signs. The consistency of the five radiologists was analyzed by intraclass correlation coefficient. RESULTS The area under the curve of the combined MR signs 2 for distinguishing between ARCO stages 2 and 3A was the greatest (0.967), sensitivity and specificity were 100.00% and 88.71% respectively, and greater than 1 was the threshold. DATA CONCLUSION Combined MR signs 2 has great values in distinguishing between ARCO stages 2 and 3A in ONFH, thus helping clinical therapy. LEVEL OF EVIDENCE 4 TECHNICAL EFFICACY: Stage 2.

BACKGROUND Spinal dural arteriovenous fistula (SDAVF) is an extremely rare vascular malformation of the central nervous system that is often confused with degenerative spinal disorders due to similar early symptoms and clinical features. Here, we report a case of SDAVF recurrence 8 years after lumbar spine surgery and summarize relevant literature. CASE SUMMARY A 54-year-old male was admitted to our hospital complaining of lower back pain, numbness in both lower extremities and intermittent claudication. Subsequent imaging identified lumbar spinal stenosis. Following surgical treatment, the patient’s symptoms significantly resolved, and he was able to perform daily activities. However, similar symptoms appeared 8 years later, followed by confirmation of SDAVF diagnosis. The patient underwent neurosurgery 7 mo after symptom onset. The follow-up period lasted 14 mo, and the patient remains with marginal neurological symptoms. CONCLUSION This case highlights the importance of prompt SDAVF diagnosis. Due to its nonspecific clinical presentation, the clinical experience of the surgeon and definitive imaging examination are indispensable. Additionally, timely neurosurgery is effective and may significantly improve patient outcomes.

BACKGROUND: Chest CT angiography (CTA) is a common clinical examination technique for children. Iterative reconstruction algorithms are often used to reduce image noise but encounter limitations under low dose conditions. Deep learning-based image reconstruction algorithms have been developed to overcome these limitations. We assessed the quantitative and qualitative image quality of thin-slice chest CTA in children acquired with low radiation dose and contrast volume by using a deep learning image reconstruction (DLIR) algorithm. METHODS: A total of 33 children underwent chest CTA with 70 kVp and automatic tube current modulation for noise indices of 11–15 based on their age and contrast volume of 0.8–1.2 mL/kg. Images were reconstructed with 50% and 100% adaptive statistical iterative reconstruction-V (ASIR-V) and high-setting DLIR (DLIR-H) at 0.625 mm slice thickness. Two radiologists evaluated images in consensus for overall image noise, artery margin, and artery contrast separately on a 5-point scale (5, excellent; 4, good; 3, acceptable; 2, sub-acceptable, and 1, not acceptable). The CT value and image noise of the descending aorta and back muscle were measured. Radiation dose and contrast volume was recorded. RESULTS: The volume CT dose index, dose length product, and contrast volume were 1.37±0.29 mGy, 35.43±10.59 mGy·cm, and 25.43±13.32 mL, respectively. The image noises (in HU) of the aorta with DLIR-H (19.24±5.77) and 100% ASIR-V (20.45±6.93) were not significantly different (P>0.05) and were substantially lower than 50% ASIR-V (29.45±7.59) (P

Pulmonary fibrosis (PF) is a type of interstitial pneumonia with complex etiology and high mortality, characterized by progressive scarring of the alveolar interstitium and myofibroblastic lesions. Recently, there has been growing appreciation of the importance of long non-coding RNAs (lncRNAs) in organ fibrosis. The aim of this study was to investigate the role of lncRNAs in lung fibrosis. We used a qRT-PCR assay to identify dysregulated lncRNAs in the lungs of mice with experimental, bleomycin (BLM)-induced pulmonary fibrosis, and a series of molecular assays to assess the role of the novel lncRNA NONMMUT060091, designated as pulmonary fibrosis inhibitor (PFI), which was significantly downregulated in lung fibrosis. Functionally, knockdown of endogenous PFI by smart silencer promoted proliferation, differentiation, and extracellular matrix (ECM) deposition in primary mouse lung fibroblasts (MLFs). In contrast, overexpression of PFI partially abrogated TGF-β1-induced fibrogenesis both in MLFs and in the human fetal lung fibroblast MRC-5 cells. Similarly, PFI overexpression attenuated BLM-induced pulmonary fibrosis compared with wild type (WT) mice. Mechanistically, using chromatin isolation by RNA purification-mass spectrometry (ChIRP-MS) and an RNA pull-down assay, PFI was found to directly bind Serine/arginine-rich splicing factor 1 (SRSF1), and to repress its expression and pro-fibrotic activity. Furthermore, silencing of SRSF1 inhibited TGF-β1-induced proliferation, differentiation, and ECM deposition in MRC-5 cells by limiting the formation of the EDA+Fn1 splicing isoform; whereas forced expression of SRSF1 by intratracheal injection of adeno-associated virus 5 (AAV5) ablated the anti-fibrotic effect of PFI in BLM-treated mice. Overall, these data reveal that PFI mitigated pulmonary fibrosis through negative regulation of the expression and activity of SRSF1 to decrease the formation of the EDA+Fn1 splicing isoform, and suggest that PFI and SRSF1 may serve as potential targets for the treatment of lung fibrosis.

SummaryN6-Methyladenosine (m6A) regulates oocyte-to-embryo transition and the reprogramming of somatic cells into induced pluripotent stem cells. However, the role of m6A methylation in porcine early embryonic development and its reprogramming characteristics in somatic cell nuclear transfer (SCNT) embryos are yet to be known. Here, we showed that m6A methylation was essential for normal early embryonic development and its aberrant reprogramming in SCNT embryos. We identified a persistent occurrence of m6A methylation in embryos between 1-cell to blastocyst stages and m6A levels abruptly increased during the morula-to-blastocyst transition. Cycloleucine (methylation inhibitor, 20 mM) treatment efficiently reduced m6A levels, significantly decreased the rates of 4-cell embryos and blastocysts, and disrupted normal lineage allocation. Moreover, cycloleucine treatment also led to higher levels in both apoptosis and autophagy in blastocysts. Furthermore, m6A levels in SCNT embryos at the 4-cell and 8-cell stages were significantly lower than that in parthenogenetic activation (PA) embryos, suggesting an abnormal reprogramming of m6A methylation in SCNT embryos. Correspondingly, expression levels of m6A writers (METTL3 and METTL14) and eraser (FTO) were apparently higher in SCNT 8-cell embryos compared with their PA counterparts. Taken together, these results indicated that aberrant nuclear transfer-mediated reprogramming of m6A methylation was involved in regulating porcine early embryonic development.

Purpose C5α receptor 1 (C5ΑR1) is associated with the development of various human cancers. However, whether it is involved in the development of hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC) is poorly understood. We explored the expression, biological role, and associated mechanisms of C5AR1 in HBV-related hepatoma cells. Materials and Methods The expression of C5ΑR1 mediated by HBV and HBV core protein (HBc) was detected in hepatoma cells. The function of nuclear factor кB (NF-κB) pathway in HBc-induced C5AR1 expression was assessed. The roles of C5ΑR1 in the activation of intracellular signal pathways, the upregulation of inflammatory cytokines, and the growth and migration of hepatoma cells mediated by HBc, were investigated. The effect of C5α in the development of HCC mediated by C5AR1 was also measured. Results C5ΑR1 expression was increased in HBV-positive hepatoma cells. Dependent on HBc, HBV enhanced the expression of C5ΑR1 at the mRNA and protein levels. Besides, HBc could promote C5ΑR1 expression via the NF-κB pathway. Based on the C5ΑR1, HBc facilitated the activation of JNK and ERK pathways and the expression and secretion of interleukin-6 in hepatoma cells. Furthermore, C5ΑR1 was responsible for enhancing the growth and migration of hepatoma cells mediated by HBc. Except these, C5α could promote the malignant development of HBc-positive HCC via C5AR1. Conclusion We provide new insight into the mechanisms of hepatocarcinogenesis mediated by HBc. C5ΑR1 has a significant role in the functional abnormality of hepatoma cells mediated by HBc, and might be utilized as a potential therapeutic target for HBV-related HCC.

The intraoperative ischemia in partial nephrectomy (PN) often leads to postoperative renal function impairment and fibrosis, which can be regulated by macrophage polarization. We have previously demonstrated that microvesicles derived from human Wharton’s Jelly mesenchymal stromal cells (hWJMSC-MVs) attenuated renal ischemia-induced renal fibrosis and contained a substantial quantity of hepatocyte growth factor (HGF). Herein, we investigated whether MSC-MVs regulate macrophage polarization and ameliorate renal fibrosis following ischemia-PN via transferring HGF. A rat model of ischemia-PN was established by 45 min of left renal ischemia followed by removal of 1/3 upper left kidney. MSC-MVs were injected through the tail vein immediately after ischemia. Renal injury biomarkers were measured and histologic analysis was performed to analyze renal injury. A co-culture model of THP-1 macrophages and MSC-MVs was utilized. The expression of M1 markers and M2 markers were determined to evaluate macrophage polarization. MSC-MV administration significantly ameliorated renal inflammation, lesions, and fibrosis in ischemia-PN rats, and promoted M2 macrophage polarization both in rat remnant renal tissues and LPS-treated THP-1 cells. These effects of MSC-MVs were compromised when HGF expression was downregulated in MSC-MVs. Collectively, MSC-MVs promote M2 macrophage polarization and attenuate renal fibrosis following ischemia-PN via transferring HGF.

Deep-ultraviolet (deep-UV) nonlinear optical (NLO) phosphates have become a continuing hot spot since the discovery of Ba3P3O10X. Herein, we report two new deep-UV NLO phosphates, KZn(PO3)3 and RbZ...

Tong Yu,1,2,* Jinglue Song,1,2,* Hui Zhou,1,2 Tingyu Wu,1,2 Zhonglin Liang,1,2 Peng Du,1,2 Chen-Ying Liu,1,2 Guanghui Wang,3 Long Cui,1,2 Yun Liu1,2 1Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai Colorectal Cancer Research Center, Shanghai, People’s Republic of China; 3Guizhou Provincial People’s Hospital, Guizhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yun Liu Tel + 86-021-25078825Email liuyun@xinhuamed.com.cnGuanghui Wang Email wangguanghui0625@163.comIntroduction: Stage I–III colorectal cancer patients are under risk of tumor recurrence and metachronous metastasis after radical surgery. An increased expression of transcription factor TEAD4 is associated with epithelial-mesenchymal transition, metastasis and poor prognosis in colorectal cancer. However, the mechanistic role of TEAD4 in driving colon cancer progression and its prognostic value in early stage of CRC remains unclear.Methods: In this study, the regulation, function and prognostic significance of TEAD4 and its new direct target gene SIX1 in CRC progression were evaluated using human tissues, molecular and cell biology.Results: We show that TEAD4 directly upregulates the expression of SIX1 at transcriptional level in CRC cells, establishing that SIX1 is a new direct target gene of TEAD4. TEAD4 promotes EMT and cell migration of CRC cells, while SIX1 knockdown attenuates this effect and SIX1 overexpression enhances this effect, indicating that SIX1 mediates the function of TEAD4 in promoting cell migration in CRC cells. Clinically, nuclear TEAD4, overexpression of SIX1 and nuclear TEAD4 with SIX1 overexpression predict poor prognosis in CRC patients.Discussion: Our study identifies TEAD4-SIX1-CDH1 form a novel signaling axis, which contributes to CRC progression, and its aberrant expression and activation predicts poor prognostic for CRC patients in stage I–III.Keywords: colorectal cancer, TEAD4, SIX1, hippo pathway

Rhabdomyosarcoma (RMS) with regional lymph node involvement has a high rate of distant metastases. Lung is the most common site, accounting for 70% of all metastases. The differential diagnosis of lung lesions due to an infectious aetiology versus metastases is usually evaluated by computed tomography (CT) or magnetic resonance imaging. However, it is rare for patients of RMS to present with infectious nodules or masses in the lung during follow-up. More importantly, infections can mimic the imaging characteristics of metastatic RMS in CT. We report two such cases where children diagnosed with head and neck embryonal RMS with lymph node metastasis, presented with pulmonary masses 0.5 and 4 years after end of treatment, without the typical signs and symptoms suggestive of an infection. Chest CT suggested a provisional diagnosis of metastases and biopsies confirmed infectious aetiology (Mycobacterium tuberculosis, Cryptococcus).

Objective: In this study, the effects and signaling pathways of Nelumbinis folium in the treatment of hyperlipidemia were analyzed based on network pharmacology and molecular docking. Materials and Methods: The main components and targets of Nelumbinis folium were searched through traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), and the active components were selected according to their oral availability and drug-like properties. The main targets of hyperlipidemia were identified using the DisGeNET database. Venny 2.1.0 was used to take the intersection of both targets, which were submitted to the STRING database to construct the protein-protein interaction network model. The Database for Annotation, Visualization and Integrated Discovery 6.7 was used to conduct gene ontology and Kyoto Encyclopedia of Gene and Genome pathway enrichment analyses of the targets. Cytoscape 3.7.1 was used to construct the component-target-pathway network. AutoDock Vina molecular docking software was used to study the binding effect and mechanism of the core components and targets of N. folium. Results: Fifteen active components of N. folium and 195 potential targets were selected through TCMSP, whereas 4216 targets for hyperlipidemia were selected from DisGeNET. Further, 138 potential cross-targets of hyperlipidemia were identified. A network of component-target-pathway was constructed. Quercetin, kaempferol, and isorhamnetin were the core components, which played an important role in anti-hyperlipidemia, mainly through the non-alcoholic fatty liver disease and insulin resistance (IR) signaling pathways. Molecular docking results showed that quercetin had the lowest docking energies with peroxisome proliferator activated receptor α, peroxisome proliferator-activated receptor γ, INSR (-6.20,-10.00, and -8.40 (kcal/mol, respectively). The binding mode was mainly hydrogen bonds and van der Waals forces. Conclusions: The active components of N. folium may regulate lipid metabolism by participating in the signaling pathways of non-alcoholic fatty liver disease and IR.

Trophectoderm (TE) barrier function is an essential prerequisite for blastocyst development. CLAUDIN7 (CLDN7), a member of CLAUDINS family, is involved in regulating intercellular exchange and cell polarity in epithelium cells. However, the role of CLDN7 in porcine early embryo development is yet to be explored. Here, we found that CLDN7 was highly conserved in different species and was widely expressed in different tissues. Remarkably, CLDN7 expression maintained a low level from GV oocyte to 4-cell stage whereas its expression exhibited a higher level from 8-cell stage onwards. Microinjection of siRNA into cytoplasm effectively knocked down expression of CLDN7 mRNA and protein in porcine embryos. CLDN7 knockdown not only significantly reduced blastocyst rates of embryos derived from parthenogenetic activation and in vitro fertilization, but also reduced number of total cells and TE cells in the resulting blastocysts. Furthermore, CLDN7 knockdown led to a significant reduction in expression of multiple genes associated with tight junction assembly and fluid accumulation. A permeability assay revealed that CLDN7 knockdown disrupted tight junction assembly and paracellular sealing in the TE epithelium. Taken together, these results demonstrate that CLDN7 regulates porcine blastocyst development via modulating trophectoderm barrier function.

Previously our study has shown that the DNA methylation (DNAm) levels at CpG sites in the pro-inflammatory cytokine gene, TNF-alpha, decrease along with aging, suggesting the potential role of DNAm in aging and heightened inflammatory process leading to increased risk for delirium. However, DNAm differences between delirium cases and non-delirium controls have not been investigated directly. Therefore, we examined genome-wide DNAm differences in blood between patients with delirium and controls to identify useful epigenetic biomarkers for delirium. Data from a total of 87 subjects (43 delirium cases) were analyzed by a genome-wide DNAm case-control association study. A genome-wide significant CpG site near the gene of LDLRAD4 was identified (p = 5.07E-8). In addition, over-representation analysis showed several significant pathways with a false discovery rate adjusted p-value < 0.05. The top pathway with a Gene Ontology term was immune response, and the second top pathway with a Kyoto Encyclopedia of Genes and Genomes term was cholinergic synapse. Significant DNAm differences related to immune/inflammatory response were shown both at gene and pathway levels between patients with delirium and non-delirium controls. This finding indicates that DNAm status in blood has the potential to be used as epigenetic biomarkers for delirium.

Background Pleuropulmonary blastomas (PPB) are rare aggressive paediatric lung malignancies and are among the most common DICER1-related disorders: it is estimated that 75–80% of children with a PPB have the DICER1 mutation. DICER1 mutations are responsible for familial tumour susceptibility syndrome with an increased risk of tumours. In approximately 35% of families with children manifesting PPB, further malignancies may be observed. Symptoms of DICER1 syndrome may vary, even within monozygotic twins. Preventive screening of carriers with DICER1 mutations is important and follow-up is undertaken as recommended by the 2016 International PPB Register. Case presentation We present two pairs of monozygotic twins. In one pair of 4-year, 2-month old girls, both with DICER1 mutation, one developed PPB(II) and her identical sibling had acute transient hepatitis. In the other pair of 19-month-old female babies, one had a history of bronchopulmonary hypoplasia and developed PPB(III) without DICER1 mutation, and her identical sibling had allergic asthma. Both patients with PPB were treated with R0 resection and received 12 cycles of postoperative chemotherapy. At the most recent review, the twins had been followed up for six and eight years, respectively, and they all remained healthy. However, the height and weight of the patients with PPB were lower than those of their respective identical sister. Conclusions PPB is rare, especially in monozygotic twins. We emphasise the importance of genetic testing and follow-up in monozygotic twins with PPB. During the follow-up, children surviving PPB should be monitored closely for growth and development disorders which caused by chemotherapy.

Healthcare workers (HCWs) are at high risk of occupational exposure to the new pandemic human coronavirus, SARS-CoV-2, and are a source of nosocomial transmission in airborne infectious isolation rooms (AIIRs). Here, we performed comprehensive environmental contamination surveillance to evaluate the risk of viral transmission in AIIRs with 115 rooms in three buildings at the Shanghai Public Health Clinical Center, Shanghai, during the treatment of 334 patients infected with SARS-CoV-2. The results showed that the risk of airborne transmission of SARS-CoV-2 in AIIRs was low (1.62%, 25/1544) due to the directional airflow and strong environmental hygiene procedures. However, we detected viral RNA on the surface of foot-operated openers and bathroom sinks in AIIRs (viral load: 55.00–3154.50 copies/mL). This might be a source of contamination to connecting corridors and object surfaces through the footwear and gloves used by HCWs. The risk of infection was eliminated by the use of disposable footwear covers and the application of more effective environmental and personal hygiene measures. With the help of effective infection control procedures, none of 290 HCWs was infected when working in the AIIRs at this hospital. This study has provided information pertinent for infection control in AIIRs during the treatment of COVID-19 patients. Electronic supplementary material The online version of this article (10.1007/s12250-020-00301-7) contains supplementary material, which is available to authorized users.

To investigate the action mechanisms of electroacupuncture (EA) on postoperative immunosuppression. Male C57BL/6 mice (5`-7 weeks old) were randomly divided into: the sham injury group, the surgical trauma stressed group, the EA group [surgery + 2/100 Hz EA at Neiguan (PC 6)], and the EA+ Nal (surgery + EA + intraperitoneal injection of naloxone). Abdominal surgical trauma stress mice model was established. EA was performed on bilateral PC 6 acupoints by an EA apparatus (2/100 Hz) for 20 min once a day for 3 days. The mRNA expressions of MOR, DOR, and KOR in thymus and L3`-L5 dorsal root ganglions (DRG) were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and the protein expressions of MOR, DOR, and KOR in thymus were measured by Western blot. Flow cytometry assay was used to detect the levels of T lymphocyte subtypes in the peripheral blood. Surgical trauma induced decreased the mRNA expression level of MOR in both thymus (P 0.05). Furthermore, T lymphocyte population of CD3+ and CD4+ was decreased in the peripheral blood after surgical trauma (both P

A novel 3D Co(II) coordination polymer (CP) {Co3(IBT)2(H2O)2}n (1) has been synthesized through the reaction of 4,5-Bis(tetrazol-5-yl)imidazole (H3IBT) with Co(NO3)2 in a mixed solvent of N,N-dimet...

Background The aim of this study was to summarize the experience and outcomes of total endovascular repair of aortic arch disease using three-dimensional (3D) printing to guide the application of modified prefenestrated/branched stent grafts. Patients and methods From April 2018 to March 2019, 17 patients with aortic arch disease were treated in our department. Five patients had an aortic arch aneurysm and 12 had undergone an aortic arch dissection. Thirteen men and 4 were women, with an average age of 57.82 ± 10.47 years. Preoperatively, a 3D-printed model of the aorta was made according to computed tomography data. Then, under the guidance of the 3D-printed aortic model, modified prefenestrated/branched stent grafts were prepared, and the diameter of the stent grafts was reduced intraoperatively by a physician for total endovascular repair. Aortic computed tomography angiography was performed 3 and 6 months after the surgery. Results All procedures were completed in one stage with no conversions to sternotomy. Among all 17 patients, the operation was successful in 16. One patient was treated with a chimney graft and a stent graft fenestrated in situ because of distortion of the stent. The success rate of the technique was 94.18%. The average operation time was 4.18 ± 1.57 hr, and no patients died. No neurologic complications, such as cerebral infarction or paraplegia, were observed during the follow-up period. Conclusions Three-Dimensional printing can be used to help guide the treatment of aortic arch disease using modified prefenestrated/branched stent grafts. This minimally invasive total treatment technique is accurate, allows quick recovery, and has a low complication rate. The short-term follow-up data show the safety and reliability of the method; however, further research and development are needed.

Pelvic fractures are often caused by high-energy injuries and accompanied by hemodynamic instability. Traditional open surgery has a large amount of bleeding, which is not suitable for patients with acute pelvic fracture. Navigation-guided, percutaneous puncture-screw implantation has gradually become a preferred procedure due to its advantages, which include less trauma, faster recovery times, and less bleeding. However, due to the complexity of pelvic anatomy, doctors often encounter some problems when using navigation to treat pelvic fractures. This article reviews the indications, contraindications, surgical procedures, and related complications of this procedure for the treatment of sacral fractures, sacroiliac joint injuries, pelvic ring injuries, and acetabular fractures. We also analyze the causes of inaccurate screw placement. Percutaneous screw placement under navigational guidance has the advantages of high accuracy, low incidence of complications and small soft-tissue damage, minimal blood loss, short hospital stays, and quick recovery. There is no difference in the incidence of complications between surgeries performed by new doctors and experienced ones. However, computer navigation technology requires extensive training, and attention should be given to avoid complications such as screw misplacement, intestinal injury, and serious blood vessel and nerve injuries caused by navigational drift.

Purpose: To summarize the experience and outcomes of total endovascular repair of thoracoabdominal aortic disease using 3-dimensional (3D) printed models to guide on-site creation of fenestrations in aortic stent-grafts. Materials and Methods: From April 2018 to March 2019, 34 patients (mean age 58±14 years; 24 men) with thoracoabdominal aortic disease were treated in our department. Nineteen patients had thoracoabdominal aortic dissection and 15 had thoracoabdominal aortic aneurysm. Preoperatively, a 3D printed model of the aorta was made according to computed tomography images. In the operating room, the main aortic stent-graft was completely released in the 3D printed model, and the position of each fenestration or branch was marked on the stent-graft. The fenestrations were then made using an electric pen. Wires were sewn to the edge of the fenestrations using nonabsorbable sutures. After customization, the aortic stent-graft was reloaded into the delivery sheath and deployed. Results: The printing process took ~5 hours (1 hour for image reconstruction, 3 hours for printing, and 1 hour for postprocessing). The physician-modified stent-grafts had a total of 107 fenestrations secured by 102 bridging stent-grafts, including 73 covered stents and 29 bare stents. The average procedure time was 5.6±1.2 hours, including a mean 1.3 hours for stent-graft customization. No renal insufficiency or paraplegia occurred. Two branch arteries were lost during the operation. One patient (3%) died 1 week after surgery from a retrograde dissection rupture. One patient developed a minor cerebral infarction postoperatively. The mean follow-up time was 8.5 months. There was 1 endoleak from a fenestration (coil embolized) and 4 distal ruptures of the aortic dissection (3 treated and 1 observed). Conclusion: Three-dimensional printing can be used to guide creation of fenestrated stent-grafts for the treatment of thoracoabdominal aortic diseases involving crucial branches. This technique appears to be more accurate than the traditional measurement method, with short-term follow-up demonstrating the safety and reliability of the method. However, further research and development are needed.

Microvesicles (MVs) derived from human umbilical cord mesenchymal stem cells (hUC-MSCs-MVs) and miR-21 were demonstrated to ameliorate renal ischemia-reperfusion injury (IRI). Since hUC-MSC-MVs contained a substantial quantity of miR-21, we speculated that miR-21 might account for a part of the therapeutic effects of hUC-MSCs-MVs. The human tubule epithelial (HK-2) cells were cultured under low oxygen (LO) condition to mimic a cellular IRI model. A rat model of unilateral renal IRI was established. A co-culture model of HK-2 cells and MSC-MVs was utilized to examine the therapeutic role of MSC-MVs in HK-2 cell apoptosis and mechanism. The results showed that hUC-MSCs-MVs inhibited LO-induced HK-2 cell apoptosis through transferring miR-21 to HK-2 cells. Mechanistically, miR-21 directly targeted and negatively regulated programmed cell death protein 4 (PDCD4) in HK-2 cells. Moreover, PDCD4 overexpression in HK-2 cells abrogated the hUC-MSCs-MVs-inhibited HK-2 cell apoptosis under LO condition. Additionally, the beneficial effect of MSC-MVs on rat renal IRI was partly eliminated when miR-21 was knocked down in MSCs. Taken together, MSC-MVs inhibit tubular epithelial cell apoptosis and ameliorate renal IRI, at least partially, via delivery of miR-21.

Decidualization is a critical process for successful embryo implantation and subsequent placenta formation. The characterization and physiological function of lncRNA during decidualization remain largely unknown. In the present study, we conducted RNA-sequencing analysis to compare gene expression between decidua of days 6 and 8, and normal pregnant endometrium (day 4). A total of 2332 high-confidence putative lncRNA transcripts were expressed. Functional clustering analysis of cis and trans lncRNA targets showed that differentially expressed lncRNAs may regulate multiple gene ontology terms and pathways that have important functions in decidualization. Subsequent analyses using qRT-PCR validated that eight of all lncRNAs were differentially regulated in mice uteri during decidualization, both in vivo and in vitro. Furthermore, we showed that differentially expressed lncRNA of Hand2os1 was specifically detected in stromal cells on days 2 to 5 of pregnancy and was strongly upregulated in decidual cells on days 6–8 of pregnancy. Similarly, Hand2os1 expression was also strongly expressed in decidualized cells following artificial decidualization, both in vivo and in vitro. In uterine stromal cells, P4 was able to significantly upregulate the expression of Hand2os1, but upregulation was impeded by RU486, whereas E2 appeared to have no regulating effect on Hand2os1 expression. Concurrently, Hand2os1 significantly promoted the decidual process in vitro and dramatically increased decidualization markers Prl8a2 and Prl3c1. Our results provide a valuable catalog for better understanding of the functional roles of lncRNAs in pregnant mouse uteri, as it relates to decidualization.

As endometrial cancer (EC) is a major threat to female health worldwide, the ability to provide an accurate diagnosis and prognosis of EC is promising to improve its treatment guidance. Since the discovery of miRNAs, it has been realized that miRNAs are associated with every cell function, including malignant transformation and metastasis. This study aimed to explore diagnostic and prognostic miRNA markers of EC. In this study, differential analysis and machine learning were performed, followed by correlation analysis of miRNA‐mRNA based on the miRNA and mRNA expression data. Nine miRNAs were identified as diagnostic markers, and a diagnostic classifier was established to distinguish between EC and normal endometrium tissue with overall correct rates >95%. Five specific prognostic miRNA markers were selected to construct a prognostic model, which was confirmed more effective in identifying EC patients at high risk of mortality compared with the FIGO staging system. This study demonstrates that the expression patterns of miRNAs may hold promise for becoming diagnostic and prognostic biomarkers and novel therapeutic targets for EC.

Long non-coding RNAs (lncRNAs) play vital roles in the metastasis and invasion of cancer cells. Systematic analysis of ovarian cancer (OvCa) expression profiles suggests that deregulation of lncRNA AC004988.1, designated promoting transition-associated lncRNA (PTAL), is involved in OvCa progression. However, the underlying mechanism of PTAL in OvCa remains unknown. In this study, we showed that PTAL was significantly upregulated in mesenchymal subtype samples compared with epithelial subtype samples from TCGA serous OvCa datasets. PTAL expression was positively correlated with the expression of fibronectin1 (FN1), whereas PTAL and FN1 were negatively correlated with miR-101 expression in the mesenchymal OvCa samples. In addition, knockdown of PTAL inhibited cell migration and invasion and blunted the progression of metastasis in vitro. Meanwhile, knockdown of PTAL increased the expression of miR-101 and subsequently inhibited the expression of FN1. Importantly, PTAL positively regulated the expression of FN1 through sponging of miR-101 and promoted OvCa cell metastasis by regulating epithelial-mesenchymal transition. Overall, our study demonstrates the role of PTAL as a miRNA sponge in OvCa and suggests that PTAL may be a potential target for preventing OvCa metastasis. Keywords: ovarian cancer, epithelial-mesenchymal transition, lncRNA PTAL, miR-101, FN1

Background Mantle cell lymphoma (MCL) is a B cell malignancy that can be aggressive and with a poor prognosis; the clinical course is heterogeneous. The epidemiology of MCL in Asia is not well documented but appears to comprise 2–6% of all lymphoma cases based on available data, with variation observed between countries. Although international guidelines are available for the treatment of MCL, there is a lack of published data or guidance on the clinical characteristics and management of MCL in patient populations from Asia. This paper aims to review the available treatment and, where clinical gaps exist, provide expert consensus from the Asian Lymphoma Study Group (ALSG) on appropriate MCL management in Asia. Body Management strategies for MCL are patient- and disease stage-specific and aim to achieve balance between efficacy outcomes and toxicity. For asymptomatic patients with clearly indolent disease, observation may be an appropriate strategy. For stage I/II disease, following international guidelines is appropriate, which include either a short course of conventional chemotherapy followed by consolidated radiotherapy, less aggressive chemotherapy regimens, or a combination of these approaches. For advanced disease, the approach is based on the age and fitness of the patient. For young, fit patients, the current practice for induction therapy differs across Asia, with cytarabine having an important role in this setting. Hematopoietic stem cell transplantation (HSCT) may be justified in selected patients because of the high relapse risk. In elderly patients, specific chemoimmunotherapy regimens available in each country/region are a treatment option. For maintenance therapy after first-line treatment, the choice of approach should be individualized, with cost being an important consideration within Asia. For relapsed/refractory disease, ibrutinib should be considered as well as other follow-on compounds, if available. Conclusion Asian patient-specific data for the treatment of MCL are lacking, and the availability of treatment options differs between country/region within Asia. Therefore, there is no clear one-size-fits-all approach and further investigation on the most appropriate sequence of treatment that should be considered for this heterogeneous disease.

We aimed to establish a discriminative gene-expression-based classifier to predict survival outcomes of T-cell lymphoblastic lymphoma (T-LBL) patients. After exploring global gene-expression profiles of progressive (n = 22) vs. progression-free (n = 28) T-LBL patients, 43 differentially expressed mRNAs were identified. Then an eleven-gene-based classifier was established using LASSO Cox regression based on NanoString quantification. In the training cohort (n = 169), high-risk patients stratified using the classifier had significantly lower progression-free survival (PFS: hazards ratio 4.123, 95% CI 2.565–6.628; p

Reactive oxygen species (ROS) have been shown to be involved in the development of insulin resistance; thus, antioxidant therapy is a promising strategy in the treatment of insulin resistance related diseases. In this study, we synthesized a high-efficiency ROS scavenger, an amino acid derivative of Gd@C82 (GF-Ala), and evaluated its effects on ROS-mediated insulin resistance in 3T3-L1 adipocytes. The exposure of adipocytes to H2O2 (generated by glucose oxidase) resulted in an elevated level of ROS, a reduced content of GSH and an increase in JNK activation, concomitantly with a decrease in insulin-stimulated PI3K, Akt and p70S6K activation and cellular glucose uptake. The pre-treatment of cells with GF-Ala suppressed H2O2-induced abnormalities in the cellular redox state and insulin signalling pathway and attenuated insulin resistance in a dose-dependent manner. Altogether, gadofullerene has potential therapeutic prospects in the prevention and treatment of insulin resistance related diseases.

SIRT6, a member of the sirtuin family, is a NAD + dependent protein deacetylase and has been implicated in transcriptional regulation of somatic cells and post-transcriptional regulation of oocyte meiosis. However, the function of cumulus cell-derived and maternal SIRT6 in meiotic maturation of porcine oocytes is not yet known. Here, we report that SIRT6 mRNA and protein exists in the oocyte and its surrounding cumulus cells during meiotic maturation. Functional studies using a specific inhibitor in cumulus-enclosed oocytes revealed important roles for SIRT6 in germinal vesicle breakdown (GVBD) and cumulus expansion. Moreover, inhibitor treatment led to a significant reduction in the rate of first polar body (PB1) extrusion and early development of parthenogenetically activated embryos. In contrast, SIRT6 inhibition in cumulus-free oocytes only resulted in a significant reduction in the rate of PB1 extrusion. Furthermore, SIRT6 dysfunction regardless of the origin in both cumulus cells and oocytes severely impaired spindle organization and chromosome alignment at the metaphase stage. Molecularly, SIRT6 inhibition in cumulus cells significantly reduced expression of genes associated with cumulus expansion and gap junctional communication and even expression levels of active phosphorylated CDK1 in oocytes. Importantly, adenylate cyclase inhibition could partially rescue GVBD and PB1 extrusion in SIRT6-inhibited cumulus-enclosed oocytes. Taken together, these results demonstrate that cumulus cell-expressed and maternal SIRT6 differentially regulates porcine oocyte meiotic maturation.

Spinal gastrin-releasing peptide receptor-expressing (GRPR+) neurons play an essential role in itch signal processing. However, the circuit mechanisms underlying the modulation of spinal GRPR+ neurons by direct local and long-range inhibitory inputs remain elusive. Using viral tracing and electrophysiological approaches, we dissected the neural circuits underlying the inhibitory control of spinal GRPR+ neurons. We found that spinal galanin+ GABAergic neurons form inhibitory synapses with GRPR+ neurons in the spinal cord and play an important role in gating the GRPR+ neuron-dependent itch signaling pathway. Spinal GRPR+ neurons also receive inhibitory inputs from local neurons expressing neuronal nitric oxide synthase (nNOS). Moreover, spinal GRPR+ neurons are gated by strong inhibitory inputs from the rostral ventromedial medulla. Thus, both local and long-range inhibitory inputs could play important roles in gating itch processing in the spinal cord by directly modulating the activity of spinal GRPR+ neurons.

Alternative splicing (AS), an important post-transcriptional regulatory mechanism that regulates the translation of mRNA isoforms and generates protein diversity, has been widely demonstrated to be associated with oncogenic processes. In this study, we systematically analyzed genome-wide AS patterns to explore the prognostic implications of AS in endometrial cancer (EC). A total of 2,324 AS events were identified as being associated with the overall survival of EC patients, and eleven of these events were further selected using a random forest algorithm. With the implementation of a generalized, boosted regression model, a prognostic AS model that aggregated these eleven markers was ultimately established with high performance for risk stratification in EC patients. Functional analysis of these eleven AS markers revealed various potential signaling pathways implicated in the progression of EC. Splicing network analysis demonstrated the notable correlation between the expression of splicing factors and AS markers in EC and further determined eight candidate splicing factors that could be therapeutic targets for EC. Taken together, the results of this study present the utility of AS profiling in identifying biomarkers for the prognosis of EC and provide comprehensive insight into the molecular mechanisms involved in EC processes. Keywords: alternative splicing, biomarker, prognostic model, endometrial cancer, overall survival

Background The objective of the current study was to investigate the clinical significance of the suprasternal space lymph node (SSLN) in pathological node-positive (pN+) papillary thyroid carcinoma (PTC) patients. Method One hundred and forty patients with pN + PTC who underwent neck dissection were enrolled into this study. SSLN was resected and used as a specimen to investigate the relationship of SSLN with several clinicopathological parameters. Results The metastasis rate of SSLN was 20.7%. On univariate analysis, we found that SSLN metastasis was significantly associated with primary cancer site (inferior portion), strap muscle invasion, level III metastasis, Level IV metastasis and lymph node metastasis between sternocleidomastoid and sternohyoid muscles. On multivariate analysis, primary cancer site (inferior portion), strap muscle invasion, Level IV metastasis and lymph node metastasis between sternocleidomastoid and sternohyoid muscles were independent risk factors for SSLN metastasis of PTC. Conclusion For pN + PTC patients, special attention should be paid to the issue of SSLN metastasis.

Conclusions: Molecular classification could provide reliable supplementary information for evaluating prognostic and contribute to treatment option decision-making in EEC patients. Fertility-sparing treatment is not recommended for EEC patients with CNH and MSI-H. Furthermore, fertility-sparing treatment can be attempted in EEC patients with CHL, but regular follow-up should be carried out to early detection of EC relapse and prevention of disease progression.