Publications by authors named "Peng Hong"

391 Publications

SARS-CoV-2 immunity and functional recovery of COVID-19 patients 1-year after infection.

Signal Transduct Target Ther 2021 10 13;6(1):368. Epub 2021 Oct 13.

Department of Nephrology, Center of Nephrology and Urology, Sun Yat-sen University Seventh Hospital, Shenzhen, Guangdong, 518107, China.

The long-term immunity and functional recovery after SARS-CoV-2 infection have implications in preventive measures and patient quality of life. Here we analyzed a prospective cohort of 121 recovered COVID-19 patients from Xiangyang, China at 1-year after diagnosis. Among them, chemiluminescence immunoassay-based screening showed 99% (95% CI, 98-100%) seroprevalence 10-12 months after infection, comparing to 0.8% (95% CI, 0.7-0.9%) in the general population. Total anti-receptor-binding domain (RBD) antibodies remained stable since discharge, while anti-RBD IgG and neutralization levels decreased over time. A predictive model estimates 17% (95% CI, 11-24%) and 87% (95% CI, 80-92%) participants were still 50% protected against detectable and severe re-infection of WT SARS-CoV-2, respectively, while neutralization levels against B.1.1.7 and B.1.351 variants were significantly reduced. All non-severe patients showed normal chest CT and 21% reported COVID-19-related symptoms. In contrast, 53% severe patients had abnormal chest CT, decreased pulmonary function or cardiac involvement and 79% were still symptomatic. Our findings suggest long-lasting immune protection after SARS-CoV-2 infection, while also highlight the risk of immune evasive variants and long-term consequences for COVID-19 survivors.
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http://dx.doi.org/10.1038/s41392-021-00777-zDOI Listing
October 2021

The Effect of Noninvasive Ventilation Support on COVID-19 Patients and Risk Factors for Invasive Ventilation - A Retrospective and Multicenter Study.

Int J Gen Med 2021 28;14:6085-6092. Epub 2021 Sep 28.

Department of Respiratory and Critical Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.

Background: Oxygen therapy (OT) is the most widely used supportive regime in patients with hypoxemic acute respiratory failure (ARF) due to severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. The aim of this study was to identify the effect of noninvasive ventilation support on coronavirus disease 2019 (COVID-19) patients and risk factors for invasive mechanical ventilation (IMV).

Methods: We retrospectively analyzed confirmed COVID-19 subjects from nine hospitals outside Wuhan. All hospitalized patients who tested positive for COVID-19 by real-time polymerase chain reaction between January 1st and March 31st, 2020, were recruited. The patients were divided into four groups based on the most advanced OT regime, including no OT, nasal oxygen therapy, high-flow nasal oxygen therapy (HFNOT) or noninvasive ventilation (NIV), and IMV. Multiple logistic regression models were performed to determine risk factors for IMV.

Results: Of the 683 recruited subjects, 315 (46.1%) subjects did not need OT, 300 (43.9%) received nasal oxygen therapy, 51 (7.5%) received HFNOT or NIV, while 17 (2.5%) subjects had to be intubated. The lactate in the OT group was higher than in the no OT group (2.7 vs 1.6, = 0.02). In addition, HFNOT or NIV patients had a higher respiratory rate, but a lower PaO2 ( < 0.001). HFNOT and NIV had an obvious beneficial effect on ARF with 75% of COVID-19 patients recovering from respiratory failure. Patients with IMV were older ( < 0.001), had a higher rate of hypertension ( < 0.001) and more secondary bacterial infections ( < 0.001) compared to those without intubation. The multivariate model showed that secondary bacterial infection (OR = 6.87, = 0.009) was independently associated with IMV failure among COVID-19 patients.

Conclusion: We identified that HFNOT and NIV had an obvious beneficial effect on ARF among COVID-19 patients. We also demonstrated that secondary bacterial infection was an independent risk factor for NIV failure in patients infected by SARS-COV2.
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http://dx.doi.org/10.2147/IJGM.S327429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490101PMC
September 2021

The fate of antibiotic resistance genes and their influential factors during excess sludge composting in a full-scale plant.

Bioresour Technol 2021 Sep 27:126049. Epub 2021 Sep 27.

College of Resources, Sichuan Agricultural University, Chengdu 611130, PR China.

The alteration of antibiotic resistance genes (ARGs) during sludge composting has been less studied in a full-scale plant, causing the miss of practical implications for understanding/managing ARGs. Therefore, this study tracked the changes of ARGs and microbial communities in a full-scale plant engaged in excess sludge composting and then explored the key factors regulating ARGs through a series of analyses. After composting, the absolute and relative abundance of ARGs decreased by 91.90% and 66.57%, respectively. Additionally, PLS-PM analysis showed that MGEs, composting physicochemical properties were the most vital factors directly influencing ARGs. Finally, network analysis indicated that Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria were the main hosts of ARGs. Based on these findings, it can be known that full-scale composting could reduce ARGs risk to an extent.
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http://dx.doi.org/10.1016/j.biortech.2021.126049DOI Listing
September 2021

fNIRS Evidence for Distinguishing Patients with Major Depression and Healthy Controls.

IEEE Trans Neural Syst Rehabil Eng 2021 Sep 23;PP. Epub 2021 Sep 23.

In recent years, major depressive disorder (MDD) has been shown to negatively impact physical recovery in a variety of patients. Functional near-infrared spectroscopy (fNIRS) is a tool that can potentially supplement clinical interviews and mental state examinations to establish a psychiatric diagnosis and monitor treatment progress. Thirty-two subjects, including 16 patients clinically diagnosed with MDD and 16 healthy controls (HCs), participated in the study. Brain oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) responses were recorded using a 22-channel continuous-wave fNIRS device while the subjects performed the emotional sound test. This study evaluated the difference between MDD patients and HCs using a variety of methods. In a comparison of the Pearson correlation coefficients between the HbO/HbR responses of each fNIRS channel and four scores, MDD patients and HCs had significantly different Athens Insomnia Scale (AIS) scores. By quantitative evaluation of the functional association, we found that MDD patients had aberrant functional connectivity compared with HCs. Furthermore, we concluded that compared with HCs, there were marked abnormalities in blood oxygen in the bilateral ventrolateral prefrontal cortex (VLPFC) and bilateral dorsolateral prefrontal cortex (DLPFC). Four statistical-based features extracted from HbO signals and four vector-based features from both HbO and HbR served as inputs to four simple neural networks (multilayer neural network (MNN), feedforward neural network (FNN), cascade forward neural network (CFNN) and recurrent neural network (RNN)). Through an analysis of combinations of different features, the combination of 4 common features (mean, STD, area under the receiver operating characteristic curve (AUC) and slope) yielded the highest classification accuracy of 89.74% for fear emotion. The combination of four novel feature (ΔCBV, ΔCOE, |L| and K) resulted in a classification accuracy of 99.94% for fear emotion. The top 10 common and novel features were selected by the ReliefF feature selection algorithm, resulting in classification accuracies of 83.52% and 91.99%, respectively. This study identified the AUC and angle K as specific neuromarkers for predicting MDD across specific depression-related regions of the prefrontal cortex (PFC). These findings suggest that the fNIRS measurement of the PFC may serve as a supplementary test in routine clinical practice to further support a diagnosis of MDD.
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http://dx.doi.org/10.1109/TNSRE.2021.3115266DOI Listing
September 2021

Multiomic analysis reveals comprehensive tumor heterogeneity and distinct immune subtypes in multifocal intrahepatic cholangiocarcinoma.

Clin Cancer Res 2021 Sep 15. Epub 2021 Sep 15.

Sun Yat-sen University First Affiliated Hospital.

Purpose: Targeted therapy and immunotherapy are transforming the treatment approach for intrahepatic cholangiocarcinoma(ICC). However, little is known about the intertumor heterogeneity(ITH) of multifocal ICC and its impacts on patient response to these treatments. We aimed to characterize the immunogenomic and epigenomic heterogeneity of multifocal ICC to guide treatment decision making.

Experimental Design: We obtained 66 tumor samples from sixteen multifocal ICC patients and characterized the tumor and immune heterogeneity using whole-exome sequencing, bulk and single-cell RNA-sequencing, methylation-microarray and multiplex immunostaining. Patients were divided into high or low ITH groups according to the median ITH index. Two independent cohorts were used to validate findings. Responses to anti-PD-1 therapy were assessed.

Results: Multifocal ICC presented considerable intertumor genomic, transcriptional and epigenomic heterogeneity within a patient in high ITH group. The immune profile among multiple tumors within a patient was relatively less heterogeneous in high- or low-ITH group, and consistent responses of multiple tumors to anti-PD-1 immunotherapy were observed. Unsupervised clustering of immune markers identified one low and one high immune subtype, with higher immune cell infiltration, closer tumor-immune cell interactions and upregulated signature expression in high immune subtype. Determining expression levels of and facilitated this immune classification and prediction of patient prognosis. Finally, promoter DNA-methylation contributed to different immune profiles of two subtypes by regulating immune-gene expression.

Conclusions: There is comprehensive heterogeneity in the genome, transcriptome and epigenome of multifocal ICC. Based on the less heterogeneous immune profile of ICC, we suggest an immune classification that stratifies patients' prognosis and may support personalized immunotherapy.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-1157DOI Listing
September 2021

Urothelial carcinoma of the renal pelvis with renal vein and inferior vena cava tumor thrombus: case series and literature review.

Transl Androl Urol 2021 Jul;10(7):2879-2888

Department of Urology, Peking University Third Hospital, Beijing, China.

Background: Urothelial carcinoma (UC) of the renal pelvis with renal vein and inferior vena cava (IVC) tumor thrombus (TT) was extremely rare. We aimed to explore the clinical and pathological characteristics, diagnosis and treatment of renal pelvis UC with renal vein and IVC TT.

Methods: From March 2016 to January 2019, eight patients of renal pelvis UC with renal vein and IVC TT were diagnosed and underwent operation in our hospital. Clinical features, operative details, pathological outcomes, and prognosis data were reviewed and collected.

Results: There were five males and three females (52-84 years old). Their main symptoms were flank pain and hematuria. According to the Mayo classification, the TT was 4 level-0 (1 left and 3 right), 2 level-I (right), and 2 level-II (right). Half the patients underwent retroperitoneal laparoscopic radical nephroureterectomy with thrombectomy, and the other underwent open procedures. The mean operative time was 298.9 minutes. Pathological outcomes revealed high-grade UC, with positive lymph nodes in 6 cases. Four patients received adjuvant chemotherapy, one target therapy and one adjuvant chemotherapy combined with immunotherapy after surgery. The mean follow-up time was 11.1 months. Three patients are alive, and two of them developed recurrence and lung metastasis.

Conclusions: Preoperative differentiation between renal pelvis UC and renal cell carcinoma with venous TT was very important for the management. Radical nephroureterectomy with thrombectomy might be a reasonable method for renal pelvis UC with venous TT. The prognosis of such cases was poor even if adjuvant therapy was scheduled.
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http://dx.doi.org/10.21037/tau-21-253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350241PMC
July 2021

Clinical profiles of SS-ILD compared with SS-NILD in a Chinese population: a retrospective analysis of 735 patients.

Ann Med 2021 12;53(1):1340-1348

Department of Respiratory and Critical Care Medicine, The Second Xiangya Hospital of Central-South University, Changsha, China.

Background: Interstitial lung disease (ILD) is a serious complication in patients with Sjögren's syndrome (SS). Most studies on primary SS (pSS) with ILD are limited in sample size, and studies on secondary SS (sSS) with ILD are rare. This study aimed to elucidate both primary and secondary SS-associated ILD (SS-ILD) based on a large cohort.

Methods: The medical records of hospitalized patients diagnosed with SS at the Second Xiangya Hospital of Central South University from January 2010 to May 2020 were retrospectively reviewed. Clinical manifestations, medical history, biological results and imaging data were collected.

Results: Of the 735 SS patients enrolled in this study, 563 (76.6%) were diagnosed with pSS, 172 (23.4%) were diagnosed with sSS. Additionally, 316 (43.0%) were diagnosed with SS-ILD. No significant difference was found between the pSS and sSS groups concerning the incidence of ILD ( = .718). Factors associated with SS-ILD were older age ( < .001), male sex ( = .032), female sex at menopause ( = .002), Raynaud's phenomenon ( < .001), low levels of albumin ( = .010) and respiratory symptoms ( < .001). The SS-ILD group showed higher counts of platelets ( < .001). The three most frequent high-resolution CT (HRCT) findings of SS-ILD were irregular linear opacities (42.7%), grid shadows (30.7%) and pleural thickening (28.5%). NSIP (56.3%) was the most frequent HRCT pattern. Compared with pSS patients with ILD (pSS-ILD) patients, sSS patients with ILD (sSS-ILD) patients had a higher incidence of proteinuria ( < .001) and hypercreatinaemia ( = .013), a higher level of erythrocyte sedimentation rate (ESR) ( = .003), low levels of complement 3 (C3) ( = .013), lymphocytes ( = .009) and leukocytes ( = .024), and worse DLCO (%Pred) ( = .035).

Conclusions: ILD is a common pulmonary involvement in both pSS patients and sSS patients. Older age, male sex, female sex at menopause, Raynaud's phenomenon, low albumin levels and respiratory symptoms are risk factors associated with SS-ILD. NSIP is important HRCT feature of SS-ILD. sSS-ILD patients showed worse laboratory results and pulmonary function.KEY MESSAGEOlder age, male sex, female sex at menopause, Raynaud's phenomenon, low albumin levels and respiratory symptoms are risk factors associated with SS-ILD.SS-ILD patients show higher counts of platelets and less purpura.sSS-ILD patients have worse laboratory results and pulmonary function.
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http://dx.doi.org/10.1080/07853890.2021.1965205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382016PMC
December 2021

Clinical experience with the treatment of retroperitoneal vascular leiomyosarcoma originating from large veins.

BMC Surg 2021 Aug 15;21(1):326. Epub 2021 Aug 15.

Department of Urology, Peking University Third Hospital, 100191, Beijing, People's Republic of China.

Background: Retroperitoneal vascular leiomyosarcoma (RVLMS) is an extremely rare disease in clinical practice, and it has poor prognosis. This article is to explore the diagnosis and treatment of RVLMS and present our experience.

Methods: Data of RVLMS patients were continuously collected in our hospital from August 2018 to February 2020: two males and two females with a median age of 56 (min-max = 33-61) years were included. Patients in whom paraganglioma could not be excluded were asked to take phenoxybenzamine before surgery. A multi-disciplinary team (MDT) meeting had been held and surgery was recommended. The operation procedures varied based on the tumor location, shape, and stage, and the core steps were "exposure of the retroperitoneum and tumor, identification of vital blood vessels, blocking the bloodstream, complete removal of the tumor and tumor thrombus, and release of blood flow". A Satinsky clamp was used to partially block the blood vessels. Follow-up was conveyed by revisits and phone calls.

Results: One patient underwent open surgery, and three patients underwent laparoscopic surgery, one of whom underwent conversion to open surgery. The procedures were finished successfully, with a median operative time of 314.5 (min-max = 224-467) mins. The median amount of intraoperative bleeding was 550 (min-max = 200-1500) ml, and three patients had transfusion during the operation. The mass was irregular in shape, with a median maximum size of 7.45 (min-max = 4.2-10.7) cm, and the pathological examination confirmed RVLMS, which has spindle-shape, high mitotic activity and atypia. One week after the operation, the median serum creatinine level was 85 (min-max = 70-99) µmol/L. The median follow-up time was 16 (min-max = 13-21) months, and 1 case reported asymptomatic recurrence.

Conclusion: Uncharacteristic manifestations and imaging features contribute to the problematic diagnosis of RVLMS. Comprehensive preoperative evaluation and careful surgical planning are essential. Multicenter research is needed in the future to reach a dominant consensus.
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http://dx.doi.org/10.1186/s12893-021-01322-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364698PMC
August 2021

Lung adenocarcinoma misdiagnosed as IgG4-related lung disease: A case report and literature review.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 Jul;46(7):767-773

Department of Respiratory and Critical Care Medicine, Second Xiangya Hospital, Central South University, Changsha 410011.

IgG4-related disease (IgG4-RD) is a recently recognized disorder characterized by elevated serum IgG4 levels and infiltration of IgG4 positive blood cells in the affected organs. However, other conditions like malignancy as well as connective tissue diseases, may show similar findings. A 56-year-old male patient visited Second Xiangya Hospital, Central South University for recurrent fever and chest pain for more than 1 month. Preliminary tests diagnosed as IgG4-related lung disease (IgG4-RLD). However, the improvement of symptoms was absent after the treatment with methylprednisolone. The patient underwent the second biopsy and the result eventually demonstrated lung adenocarcinoma. The role of IgG4 in the pathogenesis or prognosis for lung adenocarcinoma remains unclear. Therefore, a thorough evaluation of symptoms, test of specific serum markers and eventually pathological confirmation are required to avoid misdiagnosis.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2021.200887DOI Listing
July 2021

Combing machine learning and elemental profiling for geographical authentication of Chinese Geographical Indication (GI) rice.

NPJ Sci Food 2021 Jul 8;5(1):18. Epub 2021 Jul 8.

Mars Global Food Safety Center, Beijing, China.

Identification of geographical origin is of great importance for protecting the authenticity of valuable agri-food products with designated origins. In this study, a robust and accurate analytical method that could authenticate the geographical origin of Geographical Indication (GI) products was developed. The method was based on elemental profiling using inductively coupled plasma mass spectrometry (ICP-MS) in combination with machine learning techniques for model building and feature selection. The method successfully predicted and classified six varieties of Chinese GI rice. The elemental profiles of 131 rice samples were determined, and two machine learning algorithms were implemented, support vector machines (SVM) and random forest (RF), together with the feature selection algorithm Relief. Prediction accuracy of 100% was achieved by both Relief-SVM and Relief-RF models, using only four elements (Al, B, Rb, and Na). The methodology and knowledge from this study could be used to develop reliable methods for tracing geographical origins and controlling fraudulent labeling of diverse high-value agri-food products.
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http://dx.doi.org/10.1038/s41538-021-00100-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266907PMC
July 2021

Non-Structural Protein 5 of Zika Virus Interacts with p53 in Human Neural Progenitor Cells and Induces p53-Mediated Apoptosis.

Virol Sin 2021 Jul 5. Epub 2021 Jul 5.

MOE Key Laboratory of Tropical Disease Control, Centre for Infection and Immunity Study (CIIS), School of Medicine, Sun Yat-Sen University, Shenzhen, 518197, China.

Zika virus (ZIKV) infection could disrupt neurogenesis and cause microcephaly in neonates by targeting neural progenitor cells (NPCs). The tumor suppressor p53-mediated cell cycle arrest and apoptotic cell death have been suggested to be activated upon ZIKV infection, yet the detailed mechanism is not well understood. In the present study, we investigated the effects of ZIKV-encoded proteins in the activation of p53 signaling pathway and found that, among the ten viral proteins, the nonstructural protein 5 (NS5) of ZIKV most significantly activated the transcription of p53 target genes. Using the immunoprecipitation-coupled mass spectrometry approach, we identified that ZIKV-NS5 interacted with p53 protein. The NS5-p53 interaction was further confirmed by co-immunoprecipitation and GST pull-down assays. In addition, the MTase domain of NS5 and the C-terminal domain of p53 were mapped to be responsible for the interaction between these two proteins. We further showed that ZIKV-NS5 was colocalized with p53 and increased its protein level in the nuclei and able to prolong the half-life of p53. Furthermore, lentivirus-mediated expression of ZIKV-NS5 in hNPCs led to an apparent cell death phenotype. ZIKV-NS5 promoted the cleavage of PARP1 and significantly increased the cell apoptosis of hNPCs. Taken together, these findings revealed that ZIKV-NS5 is a previously undiscovered regulator of p53-mediated apoptosis in hNPCs, which may contribute to the ZIKV-caused abnormal neurodevelopment.
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http://dx.doi.org/10.1007/s12250-021-00422-7DOI Listing
July 2021

Deep Multiview Clustering via Iteratively Self-Supervised Universal and Specific Space Learning.

IEEE Trans Cybern 2021 Jun 30;PP. Epub 2021 Jun 30.

Multiview clustering seeks to partition objects via leveraging cross-view relations to provide a comprehensive description of the same objects. Most existing methods assume that different views are linear transformable or merely sampling from a common latent space. Such rigid assumptions betray reality, thus leading to unsatisfactory performance. To tackle the issue, we propose to learn both common and specific sampling spaces for each view to fully exploit their collaborative representations. The common space corresponds to the universal self-representation basis for all views, while the specific spaces are the view-specific basis accordingly. An iterative self-supervision scheme is conducted to strengthen the learned affinity matrix. The clustering is modeled by a convex optimization. We first solve its linear formulation by the popular scheme. Then, we employ the deep autoencoder structure to exploit its deep nonlinear formulation. The extensive experimental results on six real-world datasets demonstrate that the proposed model achieves uniform superiority over the benchmark methods.
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http://dx.doi.org/10.1109/TCYB.2021.3086153DOI Listing
June 2021

Spatial differentiation and driving mechanism of rural water security in typical "engineering water depletion" of karst mountainous area-A lesson of Guizhou, China.

Sci Total Environ 2021 Nov 9;793:148387. Epub 2021 Jun 9.

School of Electronic Information, Chongqing Institute of Engineering, Chongqing 400056, PR China.

Southwest China gets abundant rainfall, but in its rural areas, there is a severe shortage of water resources for irrigation and drinking. A case study was conducted in the Guizhou Province, which has the most concentrated karst distribution worldwide. The rural water security index was constructed, and Geodetector and ArcGIS were employed to systematically analyze the status quo, spatial differentiation, and driving mechanism of water security in rural areas of Guizhou in 2016. The results showed that (1) there was obvious spatial variation in the rural water security index in the study area, with only 3.85% of areas being maximally safe, and 20.51%, 35.89%, 15.38%, and 24.36% being sub-optimally safe, moderately safe, unsafe, and extremely unsafe, respectively. The spatial distribution of the rural water security index, it generally coincides with a gradual decay from the economically developed areas to the periphery. The water security of the geographical environment is inferior to those of domestic water and water for agricultural production. (2) For Guizhou Province, economic and social factors, such as the disposable income of rural residents and the incidence of impoverishment, were critical factors influencing rural water security. The critical influencing factors vary greatly among prefectures; however, there are some common factors that affect rural water security, such as the incidence of impoverishment, the penetration rate of rural piped water, the percentage of primary industry, and the percentage of karst area. The maximum value of the interactive driver of the percentage of groundwater and the disposable income of rural residents was 0.812, indicating that the interaction between the high percentage of groundwater caused by karst development and the low disposable income of rural residents was the primary reason for the low rural water security. (3) Rural water security was largely influenced by poor socioeconomic development, resulting in a low level of security and the availability of public water facilities and domestic water in rural areas. Significant improvements in rural water security depend on ameliorating the water security of agricultural production and domestic water, rather than improving the geo-environmental conditions of water resources at extremely high costs.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148387DOI Listing
November 2021

Endogenous reverse transcriptase and RNase H-mediated antiviral mechanism in embryonic stem cells.

Cell Res 2021 Sep 22;31(9):998-1010. Epub 2021 Jun 22.

Centre for Infection and Immunity Study (CIIS), School of Medicine (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong, China.

Nucleic acid-based systems play important roles in antiviral defense, including CRISPR/Cas that adopts RNA-guided DNA cleavage to prevent DNA phage infection and RNA interference (RNAi) that employs RNA-guided RNA cleavage to defend against RNA virus infection. Here, we report a novel type of nucleic acid-based antiviral system that exists in mouse embryonic stem cells (mESCs), which suppresses RNA virus infection by DNA-mediated RNA cleavage. We found that the viral RNA of encephalomyocarditis virus can be reverse transcribed into complementary DNA (vcDNA) by the reverse transcriptase (RTase) encoded by endogenous retrovirus-like elements in mESCs. The vcDNA is negative-sense single-stranded and forms DNA/RNA hybrid with viral RNA. The viral RNA in the heteroduplex is subsequently destroyed by cellular RNase H1, leading to robust suppression of viral growth. Furthermore, either inhibition of the RTase activity or depletion of endogenous RNase H1 results in the promotion of virus proliferation. Altogether, our results provide intriguing insights into the antiviral mechanism of mESCs and the antiviral function of endogenized retroviruses and cellular RNase H. Such a natural nucleic acid-based antiviral mechanism in mESCs is referred to as ERASE (endogenous RTase/RNase H-mediated antiviral system), which is an addition to the previously known nucleic acid-based antiviral mechanisms including CRISPR/Cas in bacteria and RNAi in plants and invertebrates.
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http://dx.doi.org/10.1038/s41422-021-00524-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217788PMC
September 2021

Vaccinia-related kinase 2 drives pancreatic cancer progression by protecting Plk1 from Chfr-mediated degradation.

Oncogene 2021 Jul 17;40(28):4663-4674. Epub 2021 Jun 17.

Department of Neurology, Second Affiliated Hospital of Nanchang University, Nanchang, China.

As a key cell cycle regulator, polo-like kinase 1 (Plk1) has been recognized as a crucial factor involved in the progression of pancreatic cancer (PC). However, its regulatory mechanism is poorly understood. Here, we present evidence that Plk1 is a novel substrate of vaccinia-related kinase 2 (VRK2), a serine-threonine kinase that is highly expressed and predicts poor prognosis in PC. VRK2 phosphorylates Plk1 at threonine 210 and protects it from ubiquitin-dependent proteasomal degradation. We showed that mechanistically complement factor H-related protein (CFHR), as a major E3 ligase, promotes Plk1 degradation by ubiquitinating it at lysine 209. Phosphorylation of Plk1 at threonine 210 by VRK2 interferes with the interaction of Chfr with Plk1 and antagonizes Plk1 ubiquitination, thereby stabilizing the Plk1 protein. Taken together, our data reveal a mechanism of Plk1 overexpression in PC and provide evidence for targeting VRK2 as a potential therapeutic strategy.
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http://dx.doi.org/10.1038/s41388-021-01893-4DOI Listing
July 2021

Cofilin-1 promotes fibrocyte differentiation and contributes to pulmonary fibrosis.

Biochem Biophys Res Commun 2021 Aug 2;565:43-49. Epub 2021 Jun 2.

Department of Respiratory and Critical Care Medicine, The Second Xiangya Hospital of Central-South University, Changsha, Hunan, China; Research Unit of Respiratory Disease, Central-South University, Changsha, Hunan, China; The Respiratory Disease Diagnosis and Treatment Center of Hunan Province, Changsha, Hunan, China. Electronic address:

Fibrocytes originate from the bone marrow monocyte lineage and participate in the pathogenesis of pulmonary fibrosis. Research providing a comprehensive picture of fibrocytes is still limited. Cofilin-1 (CFL-1) is an important protein that regulates cell proliferation, migration and differentiation. Whether CFL-1 can induce monocyte differentiation into fibrocytes and promote the process of pulmonary fibrosis is unknown. Compared with that of healthy controls, the expression of CFL-1 was significantly increased in the plasma and peripheral blood mononuclear cells (PBMCs) from idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD) patients (P < 0.05). The percentages of peripheral blood fibrocytes in the IPF group (4.2550 ± 0.3483%) and CTD-ILD group (4.7100 ± 0.4811%) were higher than that in the control group (1.6340 ± 0.2549%) (both P < 0.05). In vitro, PBMCs transfected with siRNA-CFL-1 showed lower expression of CFL-1, and the percentage of fibrocytes was lower than that of the control (P < 0.05). PBMCs transfected with Lv-CFL-1 to increase the expression of CFL-1 showed a higher percentage of fibrocytes than the control (P < 0.05). In mice with bleomycin-induced pulmonary fibrosis, the relative expression of CFL-1 was increased, and the percentage of fibrocytes was higher than that in the saline group (P < 0.05). In bleomycin-induced mice, interference with Lv-CFL-1 decreased the expression of CFL-1, the percentage of fibrocytes was lower, and the lung tissue showed less fibrosis (P < 0.05). The overexpression of CFL-1 is associated with pulmonary fibrogenesis. CFL-1 could promote the differentiation of fibrocytes from monocyte peripheral blood mononuclear cells and promote pulmonary fibrosis.
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http://dx.doi.org/10.1016/j.bbrc.2021.05.085DOI Listing
August 2021

Brain Tumor Segmentation via Multi-Modalities Interactive Feature Learning.

Front Med (Lausanne) 2021 13;8:653925. Epub 2021 May 13.

Department of Radiology, The 1st Medical Center, Chinese PLA General Hospital, Beijing, China.

Automatic segmentation of brain tumors from multi-modalities magnetic resonance image data has the potential to enable preoperative planning and intraoperative volume measurement. Recent advances in deep convolutional neural network technology have opened up an opportunity to achieve end-to-end segmenting the brain tumor areas. However, the medical image data used in brain tumor segmentation are relatively scarce and the appearance of brain tumors is varied, so that it is difficult to find a learnable pattern to directly describe tumor regions. In this paper, we propose a novel cross-modalities interactive feature learning framework to segment brain tumors from the multi-modalities data. The core idea is that the multi-modality MR data contain rich patterns of the normal brain regions, which can be easily captured and can be potentially used to detect the non-normal brain regions, i.e., brain tumor regions. The proposed multi-modalities interactive feature learning framework consists of two modules: cross-modality feature extracting module and attention guided feature fusing module, which aim at exploring the rich patterns cross multi-modalities and guiding the interacting and the fusing process for the rich features from different modalities. Comprehensive experiments are conducted on the BraTS 2018 benchmark, which show that the proposed cross-modality feature learning framework can effectively improve the brain tumor segmentation performance when compared with the baseline methods and state-of-the-art methods.
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http://dx.doi.org/10.3389/fmed.2021.653925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158657PMC
May 2021

Predictive Role of the Apparent Diffusion Coefficient and MRI Morphologic Features on IDH Status in Patients With Diffuse Glioma: A Retrospective Cross-Sectional Study.

Front Oncol 2021 13;11:640738. Epub 2021 May 13.

Department of Radiology, The First Medical Center, Chinese PLA General Hospital, Beijing, China.

Purpose: To evaluate isocitrate dehydrogenase (IDH) status in clinically diagnosed grade II~IV glioma patients using the 2016 World Health Organization (WHO) classification based on MRI parameters.

Materials And Methods: One hundred and seventy-six patients with confirmed WHO grade II~IV glioma were retrospectively investigated as the study set, including lower-grade glioma (WHO grade II, n = 64; WHO grade III, n = 38) and glioblastoma (WHO grade IV, n = 74). The minimum apparent diffusion coefficient (ADCmin) in the tumor and the contralateral normal-appearing white matter (ADCn) and the rADC (ADCmin to ADCn ratio) were defined and calculated. Intraclass correlation coefficient (ICC) analysis was carried out to evaluate interobserver and intraobserver agreement for the ADC measurements. Interobserver agreement for the morphologic categories was evaluated by Cohen's kappa analysis. The nonparametric Kruskal-Wallis test was used to determine whether the ADC measurements and glioma subtypes were related. By univariable analysis, if the differences in a variable were significant (P<0.05) or an image feature had high consistency (ICC >0.8; κ >0.6), then it was chosen as a predictor variable. The performance of the area under the receiver operating characteristic curve (AUC) was evaluated using several machine learning models, including logistic regression, support vector machine, Naive Bayes and Ensemble. Five evaluation indicators were adopted to compare the models. The optimal model was developed as the final model to predict IDH status in 40 patients with glioma as the subsequent test set. DeLong analysis was used to compare significant differences in the AUCs.

Results: In the study set, six measured variables (rADC, age, enhancement, calcification, hemorrhage, and cystic change) were selected for the machine learning model. Logistic regression had better performance than other models. Two predictive models, model 1 (including all predictor variables) and model 2 (excluding calcification), correctly classified IDH status with an AUC of 0.897 and 0.890, respectively. The test set performed equally well in prediction, indicating the effectiveness of the trained classifier. The subgroup analysis revealed that the model predicted IDH status of LGG and GBM with accuracy of 84.3% (AUC = 0.873) and 85.1% (AUC = 0.862) in the study set, and with the accuracy of 70.0% (AUC = 0.762) and 70.0% (AUC = 0.833) in the test set, respectively.

Conclusion: Through the use of machine-learning algorithms, the accurate prediction of IDH-mutant versus IDH-wildtype was achieved for adult diffuse gliomas noninvasive MR imaging characteristics, including ADC values and tumor morphologic features, which are considered widely available in most clinical workstations.
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http://dx.doi.org/10.3389/fonc.2021.640738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155475PMC
May 2021

Development of a simplified, sensitive, and accurate LC-MS/MS method for peanut quantification in wheat flour-based dry matrices.

Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2021 Aug 28;38(8):1260-1272. Epub 2021 May 28.

Mars Global Food Safety Center, Beijing, China.

In this study, an ELISA-based method was observed to overestimate quantification of peanut in three wheat flour-based dry matrices (both raw and cooked). A reliable method using liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed to quantify peanut accurately in these matrices. This method simplified both sample preparation and quantification compared with previous approaches, by digesting peanut proteins without reduction and alkylation and using Ara h 1 to build calibration curves. A significantly increased amount of peanut peptides was detected by heating the extracts. The sensitivity and linearity were superior to most commercial ELISA kits. The limit of quantification (LOQ) was 0.31 mg/kg total peanut in wheat flour and the linear range was between 0.3 and 40 mg/kg. This LC-MS/MS method could be applied as a confirmatory method for peanut allergen management when positive ELISA results raise suspicion of contamination.
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http://dx.doi.org/10.1080/19440049.2021.1923822DOI Listing
August 2021

Pure retroperitoneal laparoscopic radical nephrectomy and thrombectomy with delayed occlusion of the proximal inferior vena cava (DOPI) technique for renal tumor with level II-III venous tumor thrombus.

BMC Cancer 2021 May 27;21(1):627. Epub 2021 May 27.

Department of Urology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, China.

Purpose: To explore the safety and effectiveness of delayed occlusion of the proximal inferior vena cava (DOPI) technique in retroperitoneal laparoscopic radical nephrectomy (LRN) and thrombectomy for renal tumor with level II-III venous tumor thrombus (VTT).

Materials And Methods: From August 2016 to October 2018, a total of 145 patients with renal tumor and VTT were admitted to our centre. Seventy-five patients underwent laparoscopic surgery, and 70 patients underwent open surgery. Among these patients, 17 patients underwent retroperitoneal LRN and thrombectomy with the DOPI technique. Clinical data were collected retrospectively, and a descriptive statistical analysis was conducted.

Results: All the patients successfully underwent retroperitoneal laparoscopic surgery. The mean operation time was 345.9 ± 182.9 min, the mean estimated blood loss was 466.7 ± 245.5 ml. Postoperative complications occurred in three patients, including two patients of Clavien grading system level IVa and one patient of level II. There were no complications related to carbon dioxide pneumoperitoneum, such as gas embolism, acidosis, and subcutaneous emphysema. During 21 months of median follow-up time, no local recurrence was found, and distant metastasis occurred in four patients. Cancer-specific death occurred in two patients.

Conclusions: The DOPI technique is safe and feasible in the treatment of renal tumor and level II-III VTT. With the DOPI technique, the procedures of dissociating and exposing proximal inferior vena cava are simplified.
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http://dx.doi.org/10.1186/s12885-021-08392-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161924PMC
May 2021

Three-day postoperative antibiotics reduces post-hepatectomy infection rate in hepatitis B virus-related hepatocellular carcinoma.

J Gastroenterol Hepatol 2021 Sep 21;36(9):2531-2539. Epub 2021 May 21.

Department of Liver Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Background And Aim: The evidences for use of postoperative antibiotics (POA) in hepatocellular carcinoma (HCC) patients who underwent hepatectomy are controversial. We aimed to explore the relationship between POA and hepatectomy-related infection in a hepatitis B virus (HBV)-related HCC population.

Methods: We retrospectively collected 934 HCC patients who underwent hepatectomy for curative intent from three tertiary hospitals in China. The incidences of postoperative infection including surgical site infection and remote site infection were recorded and calculated. Univariable and multivariable logistic regression analyses were performed to explore related factors of postoperative infection and POA. And the relationship between infection rates with different durations of POA was investigated.

Results: The overall infection rate was 8.2% (77/934), including 6.5% (61/934) of surgical site infection and 2.0% (19/934) of remote site infection. Multivariable analysis revealed that the administration of POA was negatively related with the incidence of postoperative infection significantly (odds ratio = 0.50, 95% confidence interval = 0.30 to 0.83; P = 0.008). Albumin-bilirubin score, Barcelona Clinic Liver Cancer (BCLC) stage and extent of hepatectomy were independently related to the POA. And 3-day regimen seemed to be the shortest duration of POA to gain the lowest incidence of postoperative infection.

Conclusions: Postoperative antibiotic is necessary for HBV-related HCC patients to prevent postoperative infection, especially for those with higher albumin-bilirubin score, at BCLC stage B-C, or who underwent major hepatectomy. For HBV-related HCC patients, postoperative second-generation cephalosporins, or ceftriaxone for 3 days after surgery might be proper.
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http://dx.doi.org/10.1111/jgh.15528DOI Listing
September 2021

Clinical evaluation on idiopathic pulmonary fibrosis.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 Mar;46(3):309-315

Department of Respiratory and Critical Care Medicine, Second Xiangya Hospital, Central South University, Changsha 410011, China.

Idiopathic pulmonary fibrosis (IPF) is a chronic fatal pulmonary disease characterized by complex illness condition. There is no effective treatment at present except lung transplantation. The comprehensive evaluation is helpful for the management of patients with IPF in hierarchical stages. Therefore, it is very important to evaluate IPF by various independent factors. At present, the commonly used methods for clinical evaluation on IPF include assessment of health-related quality of life, assessment of physiological function, assessment of imaging, assessment of laboratory examination, and multi-dimensional assessment system. However, there are different advantages and disadvantages on diverse evaluation methods for the evaluation of IPF.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2021.190402DOI Listing
March 2021

The architecture and application of an automatic operational model system for basin scale water environment management and design making supporting.

J Environ Manage 2021 Jul 16;290:112577. Epub 2021 Apr 16.

School of Water Resources and Hydropower, State Key Laboratory of Water Resources and Hydropower Engineering Science, Wuhan University, Wuhan, 430079, China. Electronic address:

An advanced framework for automatic water quality forecasting and water quality management design supporting was put forward. The system is designed as a flexible and extensible service-oriented architecture with data center, system control center, model center and client center. Two operational running modes, one for water environment automatic assessment and forecast and the other for situational analysis, were set to satisfy water quality management requirements. With loosely-coupled air-land-water numerical models, the weather, pollutants sources, hydrodynamic and water quality are automatically forecasted. According to philosophy of the framework, a one-stop platform with four different subsystems for the Three Gorges Reservoir Basin (TGRB) was developed and has been in operational running for more than two years. The system can accurately assessed, forecasted and perfectly displayed the current status and future character of TGRB in air, land and water environment.
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http://dx.doi.org/10.1016/j.jenvman.2021.112577DOI Listing
July 2021

Automatic epileptic seizure detection via Stein kernel-based sparse representation.

Comput Biol Med 2021 05 16;132:104338. Epub 2021 Mar 16.

Gansu Provincial Key Laboratory of Wearable Computing, School of Information Science and Engineering, Lanzhou University, Lanzhou, China; Joint Research Center for Cognitive Neurosensor Technology of Lanzhou University & Institute of Semiconductors, Chinese Academy of Sciences, Beijing, China; CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; Engineering Research Center of Open Source Software and Real-Time System (Lanzhou University), Ministry of Education, Lanzhou, China. Electronic address:

Epileptic seizure detection is of great significance in the diagnosis of epilepsy and relieving the heavy workload of visual inspection of electroencephalogram (EEG) recordings. This paper presents a novel method for seizure detection using the Stein kernel-based sparse representation (SR) for EEG recordings. Different from the traditional SR scheme that works with vector data in Euclidean space, the Stein kernel-based SR framework is constructed for seizure detection in the space of the symmetric positive definite (SPD) matrices, which form a Riemannian manifold. Due to the non-Euclidean geometry of the Riemannian manifold, the Stein kernel on the manifold permits the embedding of the manifold in a high-dimensional reproducing kernel Hilbert space (RKHS) to perform SR. In the Stein kernel-based SR framework, EEG samples are described by SPD matrices in the form of covariance descriptors (CovDs). Then, a test EEG sample is sparsely represented on the training set, and the test sample is classified as a member of the class, which leads to the minimum reconstructed residual. Finally, by using three widely used EEG datasets to evaluate the detection performance of the proposed method, the experimental results demonstrate that it achieves good classification accuracy on each dataset. Furthermore, the fast computational speed of the Stein kernel-based SR also meets the basic requirements for real-time seizure detection.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104338DOI Listing
May 2021

Roles of ompA of Citrobacter werkmanii in bacterial growth, biocide resistance, biofilm formation and swimming motility.

Appl Microbiol Biotechnol 2021 Apr 25;105(7):2841-2854. Epub 2021 Mar 25.

Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510070, People's Republic of China.

The genus Citrobacter is commonly found in environmental and industrial settings, some members of which have been used for bioremediation of heavy metals owing to the absorption ability of their biofilms. Although our previous studies have found that the outer membrane protein A (OmpA) contributes to the process of Citrobacter werkmanii biofilm formation, the underlying mechanisms remain elusive. Therefore, we deleted ompA from the genome of C. werkmanii and investigated its phenotypes in comparison to the wild type strain (WT) and the complementary strain using biochemical and molecular techniques including RNA-Seq. Our results demonstrated that the deletion of ompA led to an increase in biofilm formation on both polystyrene and glass surfaces due to upregulation of some biofilm formation related genes. Meanwhile, swimming ability, which is mediated by activation of flagellar assembly genes, was increased on semi-solid plates in the ∆ompA strain when compared with WT. Additionally, inactivation of ompA also caused increased 1,2-benzisothiazolin-3-one (BIT) resistance, differential responses to Ca stress, curli protein expression and cellulose production. Finally, ∆ompA caused differential expression of a total of 1470 genes when compared with WT, of which 146 were upregulated and 1324 were downregulated. These genes were classified into different Gene Ontology (GO) and KEGG pathways. In summary, ompA in C. werkmanii contributes to a variety of biological functions and may act as a target site to modulate biofilm formation. KEY POINTS: • ompA is a negative regulator for biofilm formation by C. werkmanii. • ompA inhibits swimming motility of C. werkmanii. • ompA deletion causes different expression profiles in C. werkmanii.
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http://dx.doi.org/10.1007/s00253-020-11057-1DOI Listing
April 2021

The role of peroxisome proliferator-activated receptor gamma and adiponectin in children with Kawasaki disease.

J Int Med Res 2021 Mar;49(3):300060521994925

Department of Paediatrics, Affiliated Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, Guangdong Province, China.

Objective: To investigate the relationship between peroxisome proliferator-activated receptor gamma (PPARγ) mRNA, serum adiponectin (ADP) and lipids in paediatric patients with Kawasaki disease (KD).

Methods: This prospective study enrolled paediatric patients with KD and grouped them according to the presence or absence of coronary artery lesions (CAL). A group of healthy age-matched children were recruited as the control group. The levels of PPARγ mRNA, serum ADP and lipids were compared between the groups. Receiver operating characteristic (ROC) curve analysis was undertaken to determine if the PPARγ mRNA level could be used as a predictive biomarker of CAL prognosis.

Results: The study enrolled 42 patients with KD (18 with CAL [CAL group] and 24 without CAL [NCAL group]) and 20 age-matched controls. PPARγ mRNA levels in patients with KD were significantly higher than those in the controls; but significantly lower in the CAL group than the NCAL group. ROC curve analysis demonstrated that the PPARγ mRNA level provided good predictive accuracy for the prognosis of CAL. There was no association between PPARγ, ADP and lipid levels.

Conclusion: There was dyslipidaemia in children with KD, but there was no correlation with PPARγ and ADP. PPARγ may be a predictor of CAL in patients with KD with good predictive accuracy.
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http://dx.doi.org/10.1177/0300060521994925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7975572PMC
March 2021

Clinical characteristics of pulmonary alveolar proteinosis.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 Feb;46(2):156-161

Department of Respiratory and Critical Care Medicine, Second Xiangya Hospital; Research Unit of Respiratory Disease, Central South University; Respiratory Disease Diagnosis and Treatment Center of Hunan Province, Changsha 410011, China.

Objectives: Pulmonary alveolar proteinosis (PAP) is a rare disease with non-specific and various clinical manifestations, often leading to misdiagnosis. This study aims to raise the awareness of this disease via summarizing the clinical characteristics, diagnosis, and therapy of PAP.

Methods: We retrospectively analyzed clinical data of 25 hospitalized cases of PAP during 2008 and 2019 in the Department of Respiratory and Critical Care Medicine of the Second Xiangya Hospital of Central South University.

Results: Cough with unkown reason and dyspnea were common clinical manifastations of PAP. Five patients had a history of occupational inhalational exposure. Sixteen patients had typical image features including ground-glass opacification of alveolar spaces and thickening of the interlobular and intralobular septa, in typical shapes called crazy-paving and geographic pattern. Fourteen patients underwent pulmonary function tests, revealing a reduction in the diffusing capacity for carbon monoxide. The positive rate of transbronchial biopsy was 95%. Five patients received the whole lung lavage and the symptoms and imaging fcauters significantly relieved after five-years follow-up.

Conclusions: PAP is characterized by radiographic pattern and pathology. Transbronchial lung biopsy is effective to make diagnosis of PAP. The whole lung lavage remains a efficient therapy.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2021.190792DOI Listing
February 2021

MicroRNA-29 mediates anti-inflammatory effects and alleviation of allergic responses and symptoms in mice with allergic rhinitis.

Allergy Asthma Clin Immunol 2021 Mar 6;17(1):24. Epub 2021 Mar 6.

Department of Otolaryngology Head and Neck Surgery, Beijing Shijitan Hospital, Capital Medical University, No. 10 Yangfangdian Railway Hospital Road, Haidian District, Beijing, 100038, China.

Background: To investigate the role of microRNA-29 (miR-29) in mice with allergic rhinitis (AR) and its underlying mechanism.

Methods: AR model was established in BALB/c mice by intraperitoneal sensitization and intranasal challenge with ovalbumin (OVA). miRNA expression was examined in the nasal mucosa tissues of mice and patients with AR, and miRNA-29 was found to be downregulated. To unveil the role of miRNA-29 in AR, it was overexpressed in the nasal mucosa of AR mice by intranasal administration of miRNA-29 agomir. The symptoms of nasal rubbing and sneezing were recorded and evaluated. miR-29 expression, OVA-specific immunoglobulin E (IgE) concentration, pro-inflammatory cytokines levels, eosinophils number, and cleaved caspase-3 and CD276 expression were examined in nasal mucosa tissues and nasal lavage fluid (NALF) by qRT-PCR, ELISA, hematoxylin and eosin staining, western blotting, or immunohistochemistry, respectively. TUNEL assay was used to analyze nasal mucosa cells apoptosis.

Results: Decreased expression of miR-29 was observed in AR, the symptoms of which were alleviated by overexpressing miR-29. In addition, overexpression of miR-29 markedly reduced the concentration of OVA-specific IgE, the levels of IL-4, IL-6, IL-10, and IFN-γ, the pathological alterations and eosinophils infiltration in the nasal mucosa. Furthermore, restoration of miR-29 expression reduced nasal mucosa cell apoptosis. Moreover, overexpression of miR-29 significantly attenuated CD276 mRNA and protein levels in nasal mucosa cells.

Conclusion: MiR-29 mediated antiallergic effects in OVA-induced AR mice by decreasing inflammatory response, probably through targeting CD276. MiRNA-29 may serve as a potential novel therapeutic target for the treatment of AR.
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http://dx.doi.org/10.1186/s13223-021-00527-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936503PMC
March 2021

Clinical evidence of an interferon-glucocorticoid therapeutic synergy in COVID-19.

Signal Transduct Target Ther 2021 03 3;6(1):107. Epub 2021 Mar 3.

Department of Nephrology, Center of Nephrology and Urology, Sun Yat-sen University Seventh Hospital, Shenzhen, Guangdong, China.

Synthetic glucocorticoid dexamethasone is the first trial-proven drug that reduces COVID-19 mortality by suppressing immune system. In contrast, interferons are a crucial component of host antiviral immunity and can be directly suppressed by glucocorticoids. To investigate whether therapeutic interferons can compensate glucocorticoids-induced loss of antiviral immunity, we retrospectively analyzed a cohort of 387 PCR-confirmed COVID-19 patients with quasi-random exposure to interferons and conditional exposure to glucocorticoids. Among patients receiving glucocorticoids, early interferon therapy was associated with earlier hospital discharge (adjusted HR 1.68, 95% CI 1.19-2.37) and symptom relief (adjusted HR 1.48, 95% CI 1.06-2.08), while these associations were insignificant among glucocorticoids nonusers. Early interferon therapy was also associated with lower prevalence of prolonged viral shedding (adjusted OR 0.24, 95% CI 0.10-0.57) only among glucocorticoids users. Additionally, these associations were glucocorticoid cumulative dose- and timing-dependent. These findings reveal potential therapeutic synergy between interferons and glucocorticoids in COVID-19 that warrants further investigation.
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http://dx.doi.org/10.1038/s41392-021-00496-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925812PMC
March 2021

Identification of a Two-m6A RNA Methylation Regulator Risk Signature as an Independent Prognostic Biomarker in Papillary Renal Cell Carcinoma by Bioinformatic Analysis.

Biomed Res Int 2021 6;2021:4582082. Epub 2021 Feb 6.

Department of Urology, Peking University Third Hospital, Beijing, China.

N6-Methyladenosine (m6A), the most common form of mRNA modification, is dynamically regulated by the m6A RNA methylation regulators, which play an important role in regulating the gene expression and phenotype in both health and disease. However, the role of m6A in papillary renal cell carcinoma (pRCC) is unknown. The purpose of this work is to investigate the prognostic value of m6A RNA methylation regulators in pRCC; thus, we can build a risk score model based on m6A RNA methylation regulators as a risk signature for predicting the prognosis of pRCC. Here, we investigated the expression and corresponding clinical data by bioinformatic analysis based on 289 pRCC tissues and 32 normal kidney tissues obtained from TCGA database. As a result, we identified the landscape of m6A RNA methylation regulators in pRCC. We grouped all pRCC patients into two clusters by consensus clustering to m6A RNA methylation regulators, but we found that the clusters were not correlated to the prognosis and clinicopathological features of pRCC. Therefore, we additionally built a two-m6A RNA methylation regulator risk score model as a risk signature by the univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression. The risk signature was constructed as follows: 0.031HNRNPC + 0.199KIAA1429. It revealed that the risk score was associated with the clinicopathological features such as pT status and pN status of pRCC. More importantly, the risk score was an independent prognostic marker for pRCC patients. Thus, m6A RNA methylation regulators contributed to the malignant progression of pRCC influencing its prognosis.
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http://dx.doi.org/10.1155/2021/4582082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884118PMC
June 2021
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