Search

Tao He,1,2,* Xiao-Yu Sun,1,2,* Meng-Han Tong,1,2 Ming-Jie Zhang,1,2 Zhi-Jun Duan1,2 1Department of Gastroenterology, the First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China; 2Dalian Central Laboratory of Integrative Neuro-Gastrointestinal Dynamics and Metabolism Related Diseases Prevention and Treatment, Dalian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhi-Jun Duan, Department of Gastroenterology, the First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Dalian, 161000, People’s Republic of China, Tel +86 83635963, Email cathydoctor@sina.comBackground and Aim: Obesity is association with elevated risks of erosive esophagitis (EE), and metabolic abnormalities play crucial roles in its development. The aim of the study was to assess the association between metabolic obesity phenotypes and the risk of EE.Methods: This retrospective study enrolled 11,599 subjects who had undergone upper gastrointestinal endoscopy at the First Affiliated Hospital of Dalian Medical University from January 1, 2008, to December 31, 2023. The enrolled individuals were grouped into four cohorts based on their metabolic health and obesity profiles, namely, metabolically healthy non-obesity (MHNO; n=2134, 18.4%), metabolically healthy obesity (MHO; n=1736, 15.0%), metabolically unhealthy non-obesity (MUNO; n=4290, 37.0%), and metabolically unhealthy obesity (MUO; n=3439, 29.6%). The relationships of the different phenotypes of metabolic obesity with the risks of developing EE in the different sexes and age groups were investigated by multivariate logistic regression analysis.Results: The MUNO, MHO, and MUO cohorts exhibited elevated risks of developing EE than the MHNO cohort. The confounding factors were adjusted for, and the findings revealed that the MUO cohort exhibited the greatest risk of EE, with odds ratios (ORs) of 5.473 (95% CI: 4.181– 7.165) and 7.566 (95% CI: 5.718– 10.010) for males and females, respectively. The frequency of occurrence of EE increased following an increase in proportion of metabolic risk factors. Subgroup analyses showed that the individuals under and over 60 years of age in the MHO, MUNO, and MUO cohorts exhibited elevated risks of developing EE. Further analysis suggested that obesity has a stronger influence on the risks of developing EE compared to metabolic disorders.Conclusion: Metabolic disorders and obesity are both related with an elevated risk of EE, in which obesity has a potentially stronger influence. Clinical interventions should target both obesity and metabolic disorders to reduce EE risk. Keywords: metabolic obesity phenotype, erosive esophagitis, metabolic disorders

Yuan He,1,2 Zhi-Jun Duan,1 Cheng-Fang Wang,2 Yu-Shan Wei,3 Ming-Xu Cai2 1Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People’s Republic of China; 2Healthcare Management Center, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People’s Republic of China; 3Department of the Scientific Research Management, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People’s Republic of ChinaCorrespondence: Zhi-Jun DuanDepartment of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People’s Republic of ChinaTel/Fax +86 41183635963Email duanzhijun12@outlook.com; cathydoctor@sina.comObjective: The present study aimed to explore the relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and gastroesophageal reflux symptoms (GERS).Methods: The present study was a cross-sectional observational study. The study population was 3002 subjects from a single hospital who underwent a health checkup from September 1, 2019, to December 31, 2020. The diagnosis of MAFLD was based on the diagnosis of fatty liver in the subject by ultrasound or computed tomography (CT) and the presence of one of the following conditions: overweight or obesity (body mass index [BMI] ≥ 23), type 2 diabetes mellitus, and metabolic abnormalities. The subjects were divided into the GERS group (n = 305) and the non-GERS group (n = 2697) based on the presence or absence of GERS, based on the GerdQ score.Results: The prevalence of MAFLD was significantly higher in the GERS group than in the non-GERS group (p = 0.001). In the univariate analysis of risk factors for GERS, MAFLD was identified as a risk factor for GERS (OR 1.5; 95% CI 1.176– 1.913; p = 0.001). With adjustment of confounding factors such as BMI, waist circumference, lipid levels, and blood pressure, the correlation between MAFLD and GERS was attenuated but still significant (OR 1.408; 95% CI 1.085– 1.826; p = 0.010).Conclusion: MAFLD might be an independent risk factor for GERS.Keywords: gastroesophageal reflux symptoms, GERD, metabolic dysfunction-associated fatty liver disease, body mass index, obesity, questionnaire

Human bocavirus (HBoV) and HBoV2, two human bocavirus species, were found in 18 and 10 of 235 nasopharyngeal aspirates, respectively, from children hospitalized with acute respiratory tract infection. Our results suggest that, like HBoV, HBoV2 is distributed worldwide and may be associated with respiratory and enteric diseases. [ABSTRACT FROM AUTHOR]

This study aims to enhance the effectiveness of high resolution manometry (HRM) and pH-impedance monitoring metrics in distinguishing between gastro-esophageal reflux disease (GERD) and non-GERD. A retrospective propensity score matching (PSM) study was conducted on 643 patients with GERD symptoms. PSM matched 134 GERD patients with 134 non-GERD controls. Body mass index (BMI), intra-esophageal pressure (IEP) and intra-gastric pressure (IGP) were significantly higher in the GERD group compared to the non-GERD group. BMI was correlated with IEP and IGP positively. IGP was positively correlated with esophagogastric (EGJ) pressure (EGJ-P) in participants with EGJ type 1 and 2, but not in participants with EGJ type 3. BMI was correlated with distal MNBI negatively. Logistic regression showed BMI as an independent risk factor for GERD. Receiver operating characteristic curve (ROC) and decision curve analysis (DCA) showed that BMI adjusted EGJ contractile integral (EGJ-CI) and BMI adjusted MNBI were superior to the corresponding original ones in predicting GERD susceptibility. According to the findings, BMI and IGP are the main factors contributing to the development of GERD. BMI affects IEP through the adaptive response of EGJ-P to IGP. Incorporating BMI into the calculations of EGJ-CI and MNBI can improve their ability in predicting GERD susceptibility., (© 2024. The Author(s).)

Objective: To investigate the clinicopathological characteristics of plurihormonal PIT1-lineage pituitary neuroendocrine tumors. Methods: Forty-eight plurihormonal PIT1-lineage tumors were collected between January 2018 and April 2022 from the pathological database of Sanbo Brain Hospital, Capital Medical University. The related clinical and imaging data were retrieved. H&E, immunohistochemical and special stains were performed. Results: Out of the 48 plurihormonal PIT1-lineage tumors included, 13 cases were mature PIT1-lineage tumors and 35 cases were immature PIT1-lineage tumors. There were some obvious clinicopathological differences between the two groups. Clinically, the mature plurihormonal PIT1-lineage tumor mostly had endocrine symptoms due to increased hormone production, while a small number of immature PIT1-lineage tumors had endocrine symptoms accompanied by low-level increased serum pituitary hormone; patients with the immature PIT1-lineage tumors were younger than the mature PIT1-lineage tumors; the immature PIT1-lineage tumors were larger in size and more likely invasive in imaging. Histopathologically, the mature PIT1-lineage tumors were composed of large eosinophilic cells with high proportion of growth hormone expression, while the immature PIT1-lineage tumors consisted of chromophobe cells with a relatively higher expression of prolactin; the mature PIT1-lineage tumors had consistently diffuse cytoplasmic positive staining for keratin, while the immature PIT1-lineage tumors had various expression for keratin; the immature PIT1-lineage tumors showed more mitotic figures and higher Ki-67 proliferation index; in addition, 25.0% (12/48) of PIT1-positive plurihormonal tumors showed abnormal positive staining for gonadotropin hormones. There was no significant difference in the progression-free survival between the two groups ( P =0.648) by Kaplan-Meier analysis. Conclusions: Plurihormonal PIT1-lineage tumor belongs to a rare type of PIT1-lineage pituitary neuroendocrine tumors, most of which are of immature lineage. Clinically increased symptoms owing to pituitary hormone secretion, histopathologically increased number of eosinophilic tumor cells with high proportion of growth hormone expression, diffusely cytoplasmic keratin staining and low proliferative activity can help differentiate the mature plurihormonal PIT1-lineage tumors from the immature PIT1-lineage tumors. The immature PIT1-lineage tumors have more complicated clinicopathological characteristics.

The microalgae culture in mixing sewage with different characteristics may significantly improve biomass production and nutrients recycling efficiency. In this study, three waste organic wastewater including molasses, alcohol and glycerol wastewater were mixed with anaerobic soybean wastewater as mediums for microalgae culture. The optimal mixture of molasses, alcohol and glycerol wastewater was at an initial carbon-nitrogen ratio of 7:1, 5:1 and 10:1, improving biomass production by 60.4%, 31.3% and 68.7%, respectively. The removal efficiencies of organics, ammonia nitrogen and phosphorus at optimal mixture were 54.8-62.4%, 79.5-99.1% and 49.3-61.5%, and the removal rates increased by 340-630%, 27.5-66.3% and 36.3-70.2% compared to the blank culture. In addition, the culture in mixed wastewater increased lipids contrast by 0.7-1.3 times, while achieving higher saturation in fatty acids. The results suggested that microalgae culture using mixed wastewater was a strategy for high biomass production and nutrients recycling efficiency., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The incidence of obesity in the population is gradually increasing. Obesity can cause a variety of complications in the digestive system such as gastroesophageal reflux disease, and impacts the integrity of the esophageal mucosal barrier and esophageal motility. However, not many studies have focused on the effect of varying degrees of obesity on the esophagus. A total of 611 participants were included in this study. We divided them into three groups according to their body mass index (BMI): the normal weight group, the overweight group, and the obesity group. We performed a retrospective comparison between groups based on indicators from high resolution esophageal manometry (HREM) and 24-hour pH impedance monitoring, and did a correlation analysis on multiple indicators such as esophageal mucosal barrier, esophageal motility, and acid reflux. The mean nocturnal baseline impedance (MNBI) in the overweight and obesity groups was lower than that in the normal group. The MNBI of the subjects in Z5-Z6 channels in the overweight group was significantly lower than that in the normal group. With respect to Z3-Z6 channels, MNBI values in the obesity group were significantly lower than those in the normal group. 'The acid exposure time (AET), the DeMeester scores (DMS) and 24-hour total reflux episodes was significantly higher in the obesity group than those in the normal and overweight groups. The upper esophageal sphincter (UES) residual pressure, and intrabolus pressure (IBP) in the overweight and obesity groups were significantly higher than those in the normal group. In addition, lower esophageal sphincter (LES) resting pressure, and esophagogastric junction contractile integral (EGJ-CI) in the obesity group were significantly higher than those in the normal group. We found that increase in body weight affected the integrity of esophageal mucosa, and different degrees of increase associated with different degrees and different aspects of changes in esophageal motility.

Group H Rotavirus (RVH) is associated with human diarrhea gastroenteritis. The interferon (IFN) response induced by RVH remains unclear. In this study, we first studied the characteristic feature of RVH and found J19 strain of RVH grew less efficiently compared with the G6P1 strain of RVA. Next, we found that infection with the J19 virus resulted in the secretion of IFN-λ1, but not IFN-β, while both IFN-β and IFN-λ1 could inhibit J19 replication significantly in Caco-2 cells. NSP1 played an important role in the suppression of type I and type III IFN response, and NSP5 protein significantly inhibited activation of IFN-λ1. J19 NSP1 suppressed the induction of IFN-β obviously than G6P1 NSP1, while G6P1 NSP1 reduced IFN-λ1 induction to the greatest extent compared with G9P8, Wa, and J19 NSP1s. Our studies reveal the propagation feature of RVH and interferon induction and suppression by group H rotavirus., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Noroviruses (NoVs) are the primary cause of acute gastroenteritis worldwide. Histo-blood group antigens (HBGAs) are receptors or attachment factors that affect the prevalence and host susceptibility of NoVs. GII.6 NoV is one of the predominant genotypes in humans, which recognizes the type ABO secretor of HBGAs. However, the structural basis of GII.6 NoV's interaction with HBGAs receptors remains elusive. In this study, we investigated the binding features of the GII.6 strain to HBGAs using saliva- and glycan-ELISA assays and characterized the molecular basis of the GII.6 virus that recognizes H disaccharide. We showed that the GII.6 ​P domain recognized some A and O secretor's saliva samples, most B secretor's saliva samples, and H disaccharide antigen, but did not bind non-secretors' saliva. Further, we determined the crystal structures of GII.6 and its complex with H disaccharides at 1.7 ​Å, revealing that the P domain of GII.6 shares the conventional binding interface and mode of GII HBGAs. Single residue mutations at the GII.6-H binding sites could inhibit the binding of GII.6 to HBGAs, demonstrating that the interaction residues were crucial in maintaining NoV-glycan integrity. Finally, structural and sequence analyses showed that the major residues of the GII.6-H interaction were conserved among NoVs in the GII genogroup. Taken together, our study characterized the functional and structural features of GII.6 that allow it to interact with HBGAs, and shed light on NoV evolution, epidemiology, and anti-viral drug development., (Copyright © 2022 The Authors. Publishing services by Elsevier B.V. All rights reserved.)

Background: Globally, rotavirus is a leading cause of severe acute gastroenteritis among children aged under 5 years and has a significant economic cost. Currently, rotavirus vaccines are only included in the private market in China. This study aimed to assess the cost-benefit of including a three-dose rotavirus vaccine in China's National Immunization Program (NIP)., Methods: A decision tree Markov model was constructed to evaluate the cost-benefit of universal immunization with three doses of rotavirus vaccine for a 2019 birth cohort of Chinese children. Costs of the universal vaccination program included vaccine price, vaccine wastage, vaccine administration, and indirect costs. All costs were discounted at 3 % per year and converted from 2019 Chinese Yuan to 2019 USD using the 2019 exchange rate., Results: For the 2019 birth cohort of Chinese infants, inclusion of RotaTeq in NIP was estimated to prevent 5,677,911 cases of rotavirus infection, with net savings of $1.1 billion in total societal costs. A cost of $17.55 per vaccine dose was the threshold at which inclusion of rotavirus vaccine in NIP would be cost-saving., Conclusions: Introducing rotavirus vaccine into the China NIP would have significant costs from a societal perspective at the current private market price., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Ferns are one of the prevalent species of wild edible plants but one of the least explored terrestrial plants. Therefore, the aim of this study was to assess the nutrient composition, polyphenol profile and antioxidative properties of four wild edible ferns commonly utilized in northeastern China. We studied the content of ash, polysaccharide, protein, fat and mineral elements of the samples. Furthermore, the samples were found to have good total phenolic and total flavonoid contents and some level of antioxidant capacity as determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline) 6-sufonic acid (ABTS) and ferric reducing antioxidant power (FRAP). They also exhibited different specific accumulation of polyphenol profiles, estimated by liquid chromatography/mass spectrometry (LC/MS). Significance analysis revealed a significant correlation between individual phenolic compounds and the antioxidant activity of the ferns. The results of the study suggest that wild edible ferns are rich in nutritional value and have potential as a natural source of antioxidants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To investigate the clinicopathological characteristics of H3K27-altered diffuse midline glioma (DMG), and to analyze DMG's prognostic factors, and subsequently, to study the possibility of using NTRK as a therapeutic target for DMG. Methods: A total of 232 DMG diagnosed at the Sanbo Brain Hospital, Capital Medical University, Beijing, China from July 2016 to March 2021 were collected. Their clinical, radiological and pathological features, the ratio of MGMT promoter methylation, expression of NTRK, and characteristics of NTRK gene fusion were analyzed. The prognostic values of different factors were also studied, including age, tumor location, histological grade, gene and protein expression of NTRK, and postoperative adjuvant therapy. Results: Among the 232 DMG cases, there were 8 patients with both primary and relapse tumors on the record. Thus, a total of 224 patients were analyzed, including 118 males and 106 females. There were 126 adults (>18 years of age) and 98 children (≤18 years of age). Notably, the most frequent location was thalamus (41/126, 32.5%) in adults, but brainstem (59/96, 60.2%) in children. The lesions showed T1 hypointensity or isointensity, and T2 hyperintensity. However, contrast enhancement patterns of the tumors varied, with many tumors lacking contrast-enhancing. The histological grades included grade 2 (9/224, 4.0%), grade 3 (41/224, 18.3%) and grade 4 (174/224, 77.7%). Two hundred and twenty-four DMGs were diffusely positive for H3K27M and negative for H3K27me3. The ratio of MGMT promoter methylation was low (1/45, 2.2%). One hundred and seventy-seven of the 224 cases (177/224, 79.0%) were positive for NTRK. Fifty cases were analyzed using fluorescence in situ hybridization. Among them, five DMGs (positive rate, 10.0%) were NTRK fusion positive. This study showed that there were no differences between adult and pediatric DMGs in histological grading, expression of NTRK, and NTRK gene fusion. One hundred and fifty-nine patients were included in the follow-up analysis ( P >0.05). During the follow-up period, 109/159 patients (69.6%) died of the disease, with a median survival time of 12 months (range 1 to 55 months). Univariate log-rank analysis showed that age, location, surgical procedure and postoperative adjuvant therapy were associated with overall survivals of the DMG patients ( P <0.05). Conclusions: The prognosis of DMG is poor overall. There are differences between adult and pediatric DMGs in anatomic location and prognosis, but not in other features. NTRK1 gene fusion is detected in 10.0% of the tumors. It suggests that TRK inhibitor might be a choice for treating DMG.

Objective: To investigate the clinicopathological characteristics and differential diagnosis of pediatric SMARCB1/INI1-deficient poorly differentiated chordoma (PDC) of the skull base. Methods: Five cases of SMARCB1/INI1-deficient PDC were identified in 139 cases of chordoma diagnosed in Sanbo Brain Institute, Capital Medical University, Beijing, China from March 2017 to March 2021. The clinical and imaging data of the 5 PDCs were collected. H&E and immunohistochemical staining, and DNA methylation array were used, and the relevant literatures were reviewed. Results: All 5 PDCs were located at the clivus. The average age of the patients was 6.4 years, ranging from 3 to 16 years. Three patients were female and two were male. Morphologically, in contrast with classical chordomas, they presented as epithelioid or spindle tumor cells organized in sheets or nests, with necrosis, active mitoses, and infiltration into surrounding tissue. All cases showed positivity of CKpan, EMA, vimentin and brachyury (nuclear stain), and loss of nuclear SMARCB1/INI1 expression. S-100 protein expression was not frequent (2/5). Ki-67 proliferative index was high (20%-50%). All cases had over-expressed p53. It was necessary to differentiate SMARCB1/INI1-dificient PDC from SMARCB1/INI1-dificient tumors occurring at skull base of children or the tumors with epithelial and spindle cell morphological features. The 3 PDCs with DNA methylation testing showed the methylation profiles different from the pediatric atypical teratoid/rhabdoid tumors. They formed an independent methylation profile cluster. The clinical prognosis of the 5 patients was poor, and the overall survival time was 2-17 months. Conclusions: PDC is a special subtype of chordoma, which often affects children and occurs in the clivus. The PDC shares epithelioid or spindle cell morphologic features which are different from the classic chordoma. Besides the typical immunohistochemical profile of chordoma, PDC also has loss of nuclear SMARCB1/INI1 expression and distinct epigenetic characteristics.

At the end of 2019, A new type of beta-CoV, SARS-CoV-2 emerged and triggered the COVID-19 pandemic, which spread overwhelmingly around the world in less than a year. However, the origin and direct ancestral viruses of SARS-CoV-2 remain unknown. RaTG13, a novel coronavirus found in bats in China's Yunnan Province, is the closest relative virus of the SARS-CoV-2 identified so far. In this study, a new SARS-CoV-2 related virus, provisionally named PrC31, was discovered in Yunnan province by retrospectively analyse bat next generation sequencing (NGS) data of intestinal samples collected in 2018. PrC31 shared 90.7% and 92.0% nucleotide identities to the genomes of SARS-CoV-2 and the bat SARSr-CoV ZC45, respectively. Sequence alignment of PrC31 showed that several genomic regions, especially orf1a and orf8 had the highest homology with those corresponding genomic regions of SARS-CoV-2 than any other related viruses. Phylogenetic analysis indicated that PrC31 shared a common ancestor with SARS-CoV-2 in evolutionary history. The differences between the PrC31 and SARS-CoV-2 genomes were mainly manifested in the spike genes. The amino acid homology between the receptor binding domains of PrC31 and SARS-CoV-2 was only 64.2%. Importantly, recombination analysis revealed that PrC31 underwent multiple complex recombination events (including three recombination breakpoints) involving the SARS-CoV and SARS-CoV-2 sub-lineages, indicating that PrC31 evolved from yet-to-be-identified intermediate recombination strains. Combined with previous studies, it is revealed that the beta-CoVs may possess a more complex recombination mechanism than we thought.

Purpose: To evaluate viral loads in children with human adenovirus (HAdV) pneumonia at different stages of disease and compare the viral load between upper and lower respiratory tract samples., Methods: We prospectively enrolled children who required invasive ventilation for HAdV pneumonia. Nasopharyngeal aspirate (NPA) and tracheal aspirate (TA) samples were collected throughout the entire period of invasive ventilation. Viral detection and quantification were performed using quantitative real-time polymerase chain reaction., Results: Ninety-four children were enrolled. The median age of the children was 12.0 months (IQR: 11.0-24.0), and > ninety percent of patients were aged between 6 and 59 months. Seven hundred and nine paired NPA-TA samples were collected. The median viral loads of the NPA and TA samples were 7.31 log10 and 7.50 log10 copies/mL, respectively. Viral loads generally decreased steadily over time. The median viral load after 1, 2, 3, and > 3 weeks of the disease course was 8.65, 7.70, 6.69, and 5.09 log10 copies/mL, respectively, in NPA samples and 8.67, 7.79, 7.08, and 5.53 log10 copies/mL, respectively, in TA samples. Viral load showed a significant negative correlation with time since symptom onset in both NPA samples (Spearman r =  - 0.607, P = 0.000) and TA samples (Spearman r =  - 0.544, P = 0.000). The predicted duration of HAdV shedding was 60.17 days in the NPA group and 65.81 days in the TA group. Viral loads in NPA and TA from the same subjects correlated well with each other (R 2  = 0.694). HAdV loads in NPA and TA were most comparable during the early phase of infection (95% limits of agreement, - 1.36 to 1.30 log10 copies/mL, R 2  = 0.746). Variation increased during the late phase of infection (i.e., in follow-up samples), with viral loads remaining significantly higher in TA than NPA., Conclusions: In children with HAdV pneumonia, viral loads in both NPA and TA steadily decreased during the course of the disease, and the predicted duration of viral shedding was more than 2 months. The HAdV DNA load of NPA is highly correlated with that of TA, especially in the initial phase of infection., (© 2021. The Author(s).)

To understand host-pathogen interactions and develop effective prevention and control strategies for human adenovirus (HAdV), it is essential to explore the characteristics of HAdV shedding. Hospitalized children <14 years who had severe HAdV pneumonia were tested for HAdV DNA by quantitative real-time PCR in nasopharyngeal aspirate (NPA). A total of 132 children were enrolled, including 102 patients with HAdV type 7 (HAdV-7) infection and 12 patients with HAdV type 3 (HAdV-3) infection. A total of 1372 qualified NPA samples were collected. There was a significant negative correlation between the viral load of HAdV and the course of the disease (Spearman r = -0.547, p = .000). HAdV-7 load decreased at a rate of 0.089 log10 copies/mL per day (95% CI: -0.096 to -0.081; R 2 = 0.332), and the duration of viral shedding was predicted to be 96.9 days (y = 8.624-0.089x). However, HAdV-3 load decreased more quickly (95% CI: - 0.229 to - 0.143; R 2 = 0.403), and the duration of viral shedding was 51.4 days (y = 9.558-0.186x). The median viral load of the HAdV-7 group at weeks 2 and 3, and more than 3 weeks postinfection was higher than that of the HAdV-3 group. No significant differences in the duration of viral shedding were found in different gender, age (>2 vs. ≤2 years), and with or without underlying diseases groups. Viral shedding in children with severe HAdV pneumonia persisted, among which HAdV-7 lasted longer than 3 months and the viral load decreased slowly than HAdV-3., (© 2021 Wiley Periodicals LLC.)

Objectives : Clinical benefits of immune-checkpoint blockade (ICB) versus standard chemotherapy have been established in unselected non-small cell lung cancer (NSCLC). However, the response to ICB therapy among patients is heterogeneous in clinical practice. Materials and Methods : We retrospectively assessed the predicitive effect of the primary and metastatic lesion spectrum (baseline sum of the longest diameters [SLD], number of metastatic sites and specific organ metastases) on the efficacy of atezolizumab over docetaxel in OAK and POPLAR trial cohorts. A decision model, termed DSO (Diameter-Site-Organ), based on the spectrum was developed and validated for guiding ICB. Results : Higher SLD (>38 mm) and more metastatic sites (≥2) were characterized with pronounced overall survival (OS) benefits from atezolizumab versus docetaxel. Specifically, adrenal gland and brain metastases were identified as favorable predictors of atezolizumab treatment. The DSO model was developed in the discovery cohort to integrate the directive effect of the primary and metastatic lesion spectrum. Remarkably, a general pattern of enhanced efficacy of atezolizumab versus docetaxel was observed along with the increase of the DSO score. For patients with DSO score > 0, atezolizumab yielded a significantly prolonged OS than docetaxel, whereas OS was generally similar between two treatments in patients with DSO score ≤ 0. Equivalent findings were also seen in the internal and external validation cohorts. Conclusions : The response to anti-PD-L1 therapy among patients varied with the primary and metastatic lesion spectrum. The DSO-based system might provide promising medication guidance for ICB treatment in NSCLC patients., (© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Bats are well-recognized reservoirs of zoonotic viruses. Several spillover events from bats to humans have been reported, causing severe epidemic or endemic diseases including severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), SARS-CoV, Middle East respiratory syndrome-CoV (MERS-CoV), henipaviruses, and filoviruses. In this study, a novel rhabdovirus species, provisionally named Rhinolophus rhabdovirus DPuer (DPRV), was identified from the horseshoe bat (Rhinolophus affinis) in Yunnan province, China, using next-generation sequencing. DPRV shedding in the spleen, liver, lung, and intestinal contents of wild bats with high viral loads was detected by real-time quantitative PCR, indicating that DPRV has tropism for multiple host tissues. Furthermore, DPRV can replicate in vitro in multiple mammalian cell lines, including BHK-21, A549, and MA104 cells, with the highest efficiency in hamster kidney cell line BHK-21, suggesting infectivity of DPRV in these cell line-derived hosts. Ultrastructure analysis revealed a characteristic bullet-shaped morphology and tightly clustered distribution of DPRV particles in the intracellular space. DPRV replicated efficiently in suckling mouse brains and caused death of suckling mice; death rates increased with passaging of DPRV in suckling mice. Moreover, 421 serum samples were collected from individuals who lived near the bat collection site and had fever symptoms within 1 year. DPRV-specific antibodies were detected in 20 (4.75%) human serum samples by indirect immunofluorescence assay. Furthermore, 10 (2.38%) serum samples were DPRV positive according to plaque reduction neutralization assay, which revealed potential transmission of DPRV from bats to humans and highlighted the potential public health risk. Potential vector association with DPRV was not found with negative viral RNA in bloodsucking arthropods. IMPORTANCE We identified a novel rhabdovirus from the horseshoe bat ( Rhinolophus thomasi ) in China with probable infectivity in humans. DPRV was isolated in vitro from several mammalian cell lines, indicating wide host tropism, excluding bats, of DPRV. DPRV replicated in the brains of suckling mice, and the death rate of suckling mice increased with passaging of DPRV in vivo . Serological tests indicated the possible infectivity of DPRV in humans and the potential transmission to humans. The present findings provide preliminary evidence for the potential risk of DPRV to public health. Additional studies with active surveillance are needed to address interspecies transmission and determine the pathogenicity of DPRV in humans.

The clinical efficiency and adverse reactions of anlotinib in metastatic colorectal cancer (mCRC) as a third-line treatment compared with chemotherapy and regorafenib or fruquintinib was explored in this study. Clinical data from 105 mCRC patients who failed at least two lines of chemotherapy were collected. The patients were divided into three groups based on their third-line therapeutic regimen: third-line chemotherapy only (group A); anlotinib (group B); and fruquintinib or regorafenib (group C). The result showed that the ORR and DCR of group B (14.29%, 85.71%) were higher than those of group A (0%, 40.00%). The ORRs of group B and group C were 14.29% and 20.00%, respectively. Group B and group C had the same DCR, 85.71%. The mean PFS values of group B (3.46 months) and group C (3.33 months) were longer than that of group A (2.25 months) (χ2=84.255, p<0.001) and the mean PFS values of group B and group C were similar (χ2=0.884, p=0.347). The mean OS of group B was 9.22 months, which was longer than that of group A (6.95 months) (χ2=38.837, p<0.001). The mean OS values of group B (9.22 months) and group C (9.38 months) were not significantly different (χ2=0.456, p=0.499). The incidences of proteinuria, hand-foot skin reaction, myelosuppression, and gastrointestinal reaction were similar between group B and group C (p=0.173, 0.188, 1.00, 0.154, respectively). Myelosuppression and gastrointestinal reaction were more common in group A than in group B and group C (p<0.001). For mCRC, anlotinib as a third-line treatment is better than chemotherapy and similar to regorafenib or fruquintinib. The associated adverse reactions are tolerable.

Human astroviruses (HAstVs) were first identified in 1975 and can be classified into three clades: classic HAstVs (HAstV 1-8), MLB (MLB1-3) and VA (VA1-5), with MLB and VA were newly identified. Recombination and a high mutation rate make HAstV as one of the rapidly evolving infectious agents. This study reported a novel identified recombinant human astrovirus (Y/1-CHN) and its long existence in two immunocompromised patients with diarrhea following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The identified Yu/1-CHN genome contains 6801 base pairs encoding three open reading frames, with ORF1a best hit to the HAstV1 (Pune strain, 97 % nucleotide identity), while ORF1b and ORF2 best hit to HAstV-5 (DL30 strain, 99 % nucleotide identity). Possible recombination breakpoint was predicted to be located in the boundary of ORF1a and ORF1b. Different quasispecies were found in the host, and the dN/dS ratios of the S and P domains were determined to be 1.189 and 1.444, respectively, suggesting a positive selection existed. Fecal samples collected in different clinical phases from the two patients were all positive for Yu/1-CHN, suggesting a long existence of the virus in the host. It was indicated that immunocompromised patients may a reservoir for astrovirus, their excreta should be monitored even after discharge from hospital., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Human noroviruses (NVs) are the leading cause of acute gastroenteritis outbreaks worldwide. The majority of outbreaks are caused by genogroup II.4 (GII.4), with new variants emerging every 2 to 4 years. Immunocompromised patients are hypothesized to be important reservoirs where new NV variants emerge. Here, we examined intra-host NV variants and assessed immune-driven NV evolution in chronically infected immunocompromised hosts. Three NV GII.4-positive samples were collected from the same patient in different clinical phases following allogeneic hematopoietic stem cell transplantation, and had viral RNA concentrations of 2.46 × 10 6 , 1.47 × 10 6 , and 2.26 × 10 6 genome copies/mL. The non-synonymous (dN) and synonymous (dS) substitution ratio of the sequences in the partial P domain were >1, indicating strong positive selection in the patient. Both the number and the frequency of the single nucleotide variants increased over time in the patient. Also, the majority of capsid amino acid changes were located at blocking epitopes and histo-blood group antigen (HBGA)-binding sites, and 11 positive selection sites were found in the capsid region, of which 8 sites were presented in blocking epitopes or HBGA-binding sites. Homodimeric P-domain capsid models also suggested a structural change in the epitopes and HBGA-binding sites. The results suggested that novel variants of NV GII.4 with HBGA and antigenic site changes were produced in the immunocompromised patient. Further functional and epidemiological studies are needed to determine whether the new variants are a risk to public health., (Copyright © 2020 Yu, Liang, Guo, Sun, Zhang, Dong and Duan.)

The discovery and analysis of pathogens carried by non-human primates are important for understanding zoonotic infections in humans. We identified a highly divergent astrovirus (AstV) from fecal matter from a rhesus monkey in China, which has been tentatively named "monkey-feces-associated AstV" (MkAstV). The full-length genome of MkAstV was determined to be 7377 nt in length. It exhibits the standard genomic AstV organization of three open reading frames (ORFs) and is most closely related to duck AstV (28%, 49%, and 35% amino acid sequence identity in ORF1a, ORF1b, and ORF2, respectively). Coincidentally, while this report was being prepared, an astrovirus sequence from Hainan black-spectacled toad became available in the GenBank database, showing 95%, 94% and 92% aa sequence identity in ORF1a, ORF1b and ORF2, respectively, to the corresponding ORFs of MkAstV. Phylogenetic analysis of ORF1a, ORF1b, and ORF2 indicated that MkAstV and the amphibian-related astroviruses formed an independent cluster in the genus Avastrovirus. The host of MkAstV remains unknown. Epidemiological and serological studies of this novel virus should be undertaken in primates, including humans.

Rodent populations are known to be reservoirs of viruses with the potential to infect humans. However, a large number of such viruses remain undiscovered. In this study, we investigated the shedding of unknown viruses in long-tailed ground squirrel (Spermophilus undulatus) feces by high-throughput sequencing. A novel and highly divergent virus related to members of the genus Hepacivirus was identified in ground squirrel liver. This virus, tentatively named RHV-GS2015, was found to have a genome organization that is typical of hepaciviruses, including a long open reading frame encoding a polyprotein of 2763 aa. Sequence alignment of RHV-GS2015 with the most closely related hepaciviruses yielded p-distances of the NS3 and NS5B regions of 0.546 and 0.476, respectively, supporting the conclusion that RHV-GS2015 is a member of a new hepacivirus species, which we propose to be named "Hepacivirus P". Phylogenetic analysis of the NS3 and NS5B regions indicated that RHV-GS2015 shares common ancestry with other rodent hepaciviruses (species Hepacivirus E, and species Hepacivirus F), Norway rat hepacivirus 1 (species Hepacivirus G), and Norway rat hepacivirus 2 (species Hepacivirus H). A phylogenetic tree including the seven previously identified rodent hepaciviruses revealed extreme genetic heterogeneity among these viruses. RHV-GS2015 was detected in 7 out of 12 ground squirrel pools and was present in liver, lung, and spleen tissues. Furthermore, livers showed extremely high viral loads of RHV-GS2015, ranging from 2.5 × 10 6 to 2.0 × 10 8 copies/g. It is reasonable to assume that this novel virus is hepatotropic, like hepatitis C virus. The discovery of RHV-GS2015 extends our knowledge of the genetic diversity and host range of hepaciviruses, helping to elucidate their origins and evolution.

Triple-negative breast cancer (TNBC) is a heterogeneous disease with a poor prognosis due to the lack of an effective targeted therapy. Histone lysine methyltransferases (KMTs) have emerged as attractive drug targets for cancer therapy. However, the function of the majority of KMTs in TNBC has remained largely unknown. In the current study, we found that KMT nuclear receptor binding SET domain protein 2 (NSD2) is overexpressed in TNBC tumors and that its overexpression is associated with poor survival of TNBC patients. NSD2 regulates TNBC cell survival and invasion and is required for tumorigenesis and tumor growth. Mechanistically, NSD2 directly controls the expression of EGFR and ADAM9, a member of the ADAM (a disintegrin and metalloproteinase) family that mediates the release of growth factors, such as HB-EGF. Through its methylase activity, NSD2 overexpression stimulates EGFR-AKT signaling and promotes TNBC cell resistance to the EGFR inhibitor gefitinib. Together, our results identify NSD2 as a major epigenetic regulator in TNBC and provide a rationale for targeting NSD2 alone or in combination with EGFR inhibitors as a targeted therapy for TNBC.

Human noroviruses (huNoVs) recognize histo-blood group antigens (HBGAs) as host susceptibility factors. GII.13 and GII.21 huNoVs form a unique genetic lineage that emerged from mainstream GII NoVs via development of a new, nonconventional glycan binding site (GBS) that binds Le a antigen. This previous finding raised the question of whether the new GII.13/21 GBS really has such a narrow glycan binding spectrum. In this study, we provide solid phenotypic and structural evidence indicating that this new GBS recognizes a group of glycans with a common terminal β-galactose (β-Gal). First, we found that P domain proteins of GII.13/21 huNoVs circulating at different times bound three glycans sharing a common terminal β-Gal, including Lec, lactose, and mucin core 2. Second, we solved the crystal structures of the GII.13 P dimers in complex with Lec and mucin core 2, which showed that β-Gal is the major binding saccharide. Third, nonfat milk and lactose blocked the GII.13/21 P domain-glycan binding, which may explain the low prevalence of GII.13/21 viruses. Our data provide new insight into the host interactions and epidemiology of huNoVs, which would help in the control and prevention of NoV-associated diseases. IMPORTANCE Evidence from both phenotypic binding assay and structural study support the observed interactions of human noroviruses (huNoVs) with histo-blood group antigens (HBGAs) as receptors or attachment factors, affecting their host susceptibility. GII.13 and GII.21 genotypes form a unique genetic lineage that differs from the mainstream GII huNoVs in their unconventional glycan binding site. Unlike the previous findings that GII.13/21 genotypes recognize only Le a antigen, we found in this study that they can interact with a group of glycans with a common terminal β-Gal, including Lec, lactose, and mucin core 2. However, this wide glycan binding spectrum in a unique binding mode of the GII.13/21 huNoVs appears not to increase their prevalence, probably due to the existence of decoy glycan receptors in human gastrointestinal tract limiting their infection. Our findings shed light on the host interaction and epidemiology of huNoVs, which would impact the strategy of huNoV control and prevention., (Copyright © 2019 Cong et al.)

Background: Noroviruses (NVs) are an important cause of acute gastroenteritis (AGE) worldwide. There are limited data on the prevalence and molecular characterization of NVs in children in Hohhot, China., Methods: Between January 2012 and December 2017, 1863 stool samples were collected at Maternal and Child Health Hospital in Hohhot. All samples were screened for NVs by real-time reverse transcription polymerase chain reaction (real-time RT-PCR)., Results: NVs were detected in 24.15% of these inpatient cases, ranging from 12.78 to 32.92% in different years. NV was detected throughout the year, with a peak in winter. Based on sequence analysis of the partial VP1 gene, the 306 identified NV strains were divided into six genotypes: GII.3 (71.24%), GII.4 (23.53%), and GII.2, GII.5, GII.6, and GII.13 (total 5.23%). Based on further sequence analysis of the RNA-dependent RNA polymerase (RdRp), GII.P12/GII.3, GII.Pe/GII.4, and GII.P4/GII.4 were identified as predominant genotypes, accounting for 92.6% of genotyped strains. The median age of the children with NV infection was 8.0 (range 0-59) months. However, children infected with GII.3 were younger (median 7.0 months) than GII.4-positive patients (median 10.0 months)., Conclusion: NV contributed greatly to AGE among hospitalized children in Hohhot in China. Continuous surveillance is important for understanding the local prevalence and characterization of NV.

ON1 is a novel genotype of human respiratory syncytial virus (HRSV) subtype A, in children with acute respiratory tract infections (ARTIs). However, there is not much data on the prevalence and clinical and molecular characterization in China.Our study is based on the children who had respiratory infections positive for RSV-A admitted by Gansu Provincial Maternity and Child-care Hospital in Lanzhou (northwestern China) during the last 7 epidemic seasons from 2010 to 2017.In our study, different strains of the novel RSV-A genotype ON1, first identified in Canada in December 2010, were first detected in Gansu Provincial Maternity and Child-care Hospital in August 2012 and then followed by an abrupt expansion in the number of ON1 variants in the beginning of 2014 and eventually replaced all other RSV-A strains from 2015 to 2017. ON1 is characterized by a 72-nt duplication in the C-terminal region of the highly variable attachment glycoprotein (G), predicted to lengthen the polypeptide with 24 amino acids, including a 23-aa duplication, which likely changes antigenicity. New N-glycosylation sites occurred within the 23-aa duplication and 24-aa insertion of the ON1 viruses in our study. Notably, RSV infections occurred later, but peaked sooner from the 2014/2015 to 2016/2017 epidemic seasons, compared with the previous 4 seasons.Our study concluded that genotype ON1 has caused larger outbreaks and became the predominate genotype for HRSV subgroup A in Lanzhou from 2013 to 2017, and became the sole genotype of RSV-A in 2015/2016 and 2016/2017. Our data indicate that northwest of China and the world will eventually be dominated by the ON1 RSV-A genotype, including the possibility for vaccine development. Based on trends seen in RSV-B BA genotype, which predominated for decades, there is a possibility to develop a vaccine for children in the next 10 years.

Background: Since H7N9 influenza A virus (H7N9) was first reported in 2013, five waves of outbreaks have occurred, posing a huge threat to human health. In preparation for a potential H7N9 epidemic, it is essential to evaluate the efficacy of anti-H7N9 drugs with an appropriate model., Methods: Well-differentiated pseudostratified human airway epithelium (HAE) cells were grown at the air-liquid interface, and the H7N9 cell tropism and cytopathic effect were detected by immunostaining and hematoxylin-eosin (HE) staining. The H7N9 replication kinetics and anti-H7N9 effect of recombinant human α2b (rhIFN-α2b) and rhIFN-λ1 were compared with different cell lines. The H7N9 viral load and interferon-stimulated gene (ISG) expression were quantified by real-time PCR assays., Results: H7N9 could infect both ciliated and non-ciliated cells within the three-dimensional (3D) HAE cell culture, which reduced the number of cilia and damaged the airways. The H7N9 replication kinetics differed between traditional cells and 3D HAE cells. Interferon had antiviral activity against H7N9 and alleviated epithelial cell lesions; the antiviral activity of rhIFN-α2b was slightly better than that of rhIFN-λ1. In normal cells, rhIFN-α2b induced a greater amount of ISG expression (MX1, OAS1, IFITM3, and ISG15) compared with rhIFN-λ1, but in 3D HAE cells, this trend was reversed., Conclusions: Both rhIFN-α2b and rhIFN-λ1 had antiviral activity against H7N9, and this protection was related to the induction of ISGs. The 3D cell culture model is suitable for evaluating interferon antiviral activity because it can demonstrate realistic in vivo-like effects.

Introduction: In China, rotavirus is the leading cause of diarrhea hospitalizations among children aged <5 years. A locally manufactured rotavirus vaccine is available for private market use, but little is known about its coverage. Given the impending availability of newer rotavirus vaccines, we evaluated intussusception rates among children aged <2 years to better understand intussusception epidemiology for future vaccine safety monitoring., Methods: We conducted a retrospective review at 4 hospitals in Chenzhou City of Hunan Province and Kaifeng City of Henan Province. We identified intussusception cases admitted during 2009-2013 by reviewing medical records with the ICD-10 discharge code for intussusception and extracting demographic and clinical information from the electronic clinical record systems., Results: During 2009-2013, 1715 intussusception hospitalizations among 1,487,215 children aged <2 years occurred in both cities. The average annual intussusception hospitalization incidence was 112.9 per 100,000 children aged <2 years (181.8 per 100,000 children <1 year; 56 per 100,000 children 1 to <2 years). Intussusception incidence was low among infants aged <3 months and peaked at age 6-8 months. No clear seasonality was observed. Ultrasound was used to diagnose 95.9% of cases. Enema reduction was performed in 80% cases; 25% of cases in Chenzhou and 16% in Kaifeng required surgical intervention. No deaths were reported. The median time between symptom onset and admission was 1 day., Conclusions: This study provides information on intussusception incidence and epidemiology in two cities of China during 2009-2013. Monitoring intussusception rates in this population will be important in the post-rotavirus vaccine era., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Rotaviruses (RVs) are a major cause of acute children gastroenteritis. The rotavirus P [10] belongs to P[I] genogroup of group A rotaviruses that mainly infect animals, while the rotavirus P [10] was mainly identified from human infection. The rotavirus P [10] is an unusual genotype and the recognition pattern of cellular receptors remains unclear., Methods: We expressed and purified the RV P [10] VP8* protein and investigated the saliva and oligosaccharide binding profiles of the protein. A homology model of the P [10] VP8* core protein was built and the superimposition structural analysis of P [10] VP8* protein on P [19] VP8* in complex with mucin core 2 was performed to explore the possible docking structural basis of P [10] VP8* and mucin cores., Results: Our data showed that rotavirus P [10] VP8* protein bound to all ABO secretor and non-secretor saliva. The rotavirus P [10] could bind strongly to mucin core 2 and weakly to mucin core 4. The homology modeling indicated that RV P [10] VP8* binds to mucin core 2 using a potential glycan binding site that is the same to P [19] VP8* belonging to P[II] genogroup., Conclusion: Our results suggested an interaction of rotavirus P [10] VP8* protein with mucin core 2 and mucin core 4. These findings offer potential for elucidating the mechanism of RV A host specificity, evolution and epidemiology.

Objective: To investigate the clinicopathologic characteristics and BRAF V600E mutation of brain tumors associated with epilepsy. Methods: Totally 250 patients with brain tumors associated with epilepsy were included from March 2008 to August 2017 retrospectively at Sanbo Brain Hospital, Capital Medical University.The clinical manifestations, histological features and BRAF V600E mutation results were collected and analyzed. Results: There were 132 males and 118 females, and the male to female ratio was 1.1∶1.0. The age of patients ranged from 2 to 67 years(mean 22 years). The tumors had obvious local space occupying effect on MRI. The temporal lobe was the most common site (44.4%, 111/250). There were 58.4% (146/250) of ganglioglioma (GG), 24.0% (60/250) of dysembryoplastic neuroepithelial tumor (DNT), 12.8% (32/250) of pleomorphic xanthoastrocytoma(PXA), 4.0% (10/250) of angiocentric glioma (AG) and 0.8% (2/250) of papillary glioneuronal tumor (PGNT). Mixed GG, PXA and DNT morphological structures were found in 9 of patients. Among 250 cases, 35 cases were accompanied by focal cortical dysplasia(FCD). BRAF V600E was seen in 43 of 74 (58.1%) GG and 13 of 28 (46.4%) PXA. The most common pathologic grade of GG, DNT, AG and PGNT was WHO I. Some of the tumor cells from GG (34 cases) showed higher proliferative activity (WHO Ⅱ/Ⅲ). Most cases of PXA were WHOⅡand high proliferative activity was seen in nine cases. Conclusions: The association of low-grade glioneuronal tumors with intractable epilepsy was well-recognized. The most common low-grade glioneuronal tumors were GG.GG may occur in any part of the central nervous system, with a predilection for temporal lobe. Each type of low-grade glioneuronal tumors has its own unique histological morphology, but some may show complex features with 2 or 3 mixed components. The occurrence of BRAF V600E mutations in GG is common, and their detection may be valuable for the diagnosis and treatment in GG.

Objective: To analyze the correlation between cognitive function and serum NPY levels in OSAHS patients, and to explore biomarkers for evaluating cognitive function in adult patients with OSAHS. To verify the validity of MoCA in evaluating cognitive function in OSAHS patients. Method: 72 patients with OSAHS and 16 healthy controls were included. Subjects were tested for PSG, MoCA, and MMSE; ELISA was used to detect serum NPY levels in subjects. After 14 days, 10 patients in the control group were randomly selected for re-testing of MoCA to detect the internal consistency, test-retest reliability and simultaneous validity of MoCA. Result: The cognitive dysfunction of OSAHS patients was manifested in visual spatial ability, language and attention. Serum NPY levels were negatively correlated with MoCA scores ( r =-0.105), and the correlation was not significant. The internal consistency of the MoCA detected by the Cronbach coefficient α is reliable (0.690), and when "directional ability" deleted,the reliability increases (0.705); In addition, both of test-retest reliability ( r =0.884, P =0.001) and simultaneous validity ( r =0.701, P <0.01) of MoCA were reliable. Conclusion: MoCA in evaluating the cognitive function of adult with OSAHS is reliable, stable and effective, and when "directional ability" deleted,the reliability increases . The cognitive dysfunction of OSAHS patients is manifested in visual spatial ability, language and attention, which is obvious with the disease of severity; serum NPY levels can reflect the severity of OSAHS; there is no significant negative correlation between serum NPY level and MoCA total score. Whether it can be used to evaluate cognitive function in OSAHS patients needs further verification.

Background: Preoperative hematological markers that indicate nutritional, coagulation, and inflammation statuses have prognostic value for gliomas. This study aimed to investigate hematological markers with regard to tumor grades, isocitrate dehydrogenase mutations (IDH), age, and sex in patients with gliomas. Methods: From 2008 to 2017, patients with a pathological diagnosis of glioma who underwent surgery were retrospectively enrolled in this study. Information from clinical records, including age, sex, preoperative experiment tests (routine blood tests, biochemistry, and coagulation examinations), pathological results, and IDH status, was collected. A univariable survival analysis was performed. Hematological factors such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte-ratio (PLR), and albumin-to-globulin (AGR) were calculated. The prognostic nutrition index (PNI) was calculated as 10 × serum albumin value (g/dl) + 0.005 × peripheral lymphocyte count (per mm 3 ). Results: Our study included 706 patients. The univariate analysis showed that age, IDH-1, and hematological factors were all significantly associated with overall survival (OS) in patients with gliomas. Our results showed that inflammation markers (NLR, PLR, and fibrinogen) were positively associated with age, whereas AGR was negatively associated with age. The PLR was significantly increased, whereas the AGR and PNI were decreased in women with gliomas, as compared with men. We found that inflammation markers increased and nutrition markers decreased with gliomas grade. However, these hematological markers did not significantly differ with IDH status. NLR was the best single hematological marker for distinguishing glioblastoma (GBM) [0.684 (0.645-0.723)], IDH-wt GBM [0.672 (0.631-0.71)] from other gliomas subtypes. Combinations of age with PNI and age with AGR were the best predictors of GBM [0.750 (0.713-0.786)] and IDH-wt GBM [0.759 (0.719-0.798)], respectively. Conclusion: Preoperative hematological marker levels vary among glioma grades and have high predictive values for GBM.

Background: Acute diarrheal illness (ADI) is an important public health problem worldwide. We estimated the morbidity, distribution, and burden of self-reported ADI in China over the last three decades., Methods: We used the keywords "diarrhea and morbidity" to identify studies published in Chinese by searching CNKI, WANFANG, Chongqing VIP, and SinoMed. Studies published in English were identified using the keywords "diarrhea, morbidity, and China" to search Pubmed/Medline, Embase, and Cochrane Library Data. All articles published before Dec 31, 2014 were included in the search. Data were extracted and the pooled 2-week incidence rate of ADI was calculated using the fixed-effects or random-effects model according to statistical testing for homogeneity. The incidences of each subgroup (organized by age, location, study period) were also calculated. Publication bias was examined using Begg's test. Data manipulation and statistical analyses were undertaken using R-2.15.1 software., Results: We estimated that the pooled 2-week prevalence of ADI in China was 2.04% (95% CI: 1.48-2.79) and that the corresponding incidence rate was 0.53 (95% CI: 0.38-0.73) episodes per person-year. The ADI rate was highest among children aged < 5 years (1.43 episodes per person-year), and it was slightly higher in males than in females (0.58 vs 0.52 episodes per person-year). From 1980 to 2012, there was a significant decrease in the incidence of ADI, from 0.82 to 0.48 episodes per person-year, but the ADI incidence was consistent over the last two decades. Additionally, the incidence of ADI was higher in rural areas and in west China and peaked in the summer months., Conclusions: The current study indicates that ADI caused a substantial disease burden in China in the last 30 years, especially in rural areas and west China, where sanitation conditions were relatively poor. These findings highlight the importance of further investigation of the specific causes of and effective preventive measures for ADI.

To establish an animal model for the newly identified Marmota Himalayana hepatovirus, MHHAV, so as to develop a better understanding of the infection of hepatitis A viruses. Five experimental woodchucks (Marmota monax) were inoculated intravenously with the purified MHHAV from wild woodchuck feces. One animal injected with PBS was defined as a control. Feces and blood were routinely collected. After the animals were subjected to necropsy, different tissues were collected. The presence of viral RNA and negative sense viral RNA was analyzed in all the samples and histopathological and in situ hybridization analysis was performed for the tissues. MHHAV infection caused fever but no severe symptoms or death. Virus was shed in feces beginning at 2 dpi, and MHHAV RNA persisted in feces for ~2 months, with a biphasic increase, and in blood for ~30 days. Viral RNA was detected in all the tissues, with high levels in the liver and spleen. Negative-strand viral RNA was detected only in the liver. Furthermore, the animals showed histological signs of hepatitis at 45 dpi. MHHAV can infect M. monax and is associated with hepatic disease. Therefore, this animal can be used as a model of HAV pathogenesis and to evaluate antiviral and anticancer therapeutics.

Preoperative plasma fibrinogen levels were associated with poor clinical outcomes in malignancies. There were few data about the prognostic value of plasma fibrinogen in glioblastomas (GBMs). The objective of our study was to investigate the association between fibrinogen and patients' clinicopathological factors and overall survival (OS). From 2008 to 2016, 315 patients with GBMs who had a surgical treatment at our institute, were retrospectively involved in this study. IDH (isocitrate dehydrogenase) mutations and ATRX (alpha thalassemia/mental retardation syndrome X-linked) loss were detected with IHC (Immunohistochemistry). The preoperative plasma fibrinogen levels ranged from 1.00 to 5.22 g/L, with a mean of were 2.57 g/L. There were increased levels of plasma fibrinogen in patients aged ≥ 65 years, secondary GBMs, IDH mutation (p = 0.033) and ATRX loss (p = 0.040). Moreover, the plasma fibrinogen level was the highest in the subtype of IDH-1 R132H wildtype - ATRX expression, which showed a shorter OS compared to the group of IDH-1 R132H mut and IDH-1 R132H wildtype - ATRX loss (p = 0.001, log-rank test). ROC curves for fibrinogen and IDH-1 R132H wildtype - ATRX expression was also plotted, and indicated a potential diagnostic value of fibrinogen in molecular pathology. Univariate analysis found that younger age, higher KPS (Karnofsky Performance Score), gross total resection, complete chemoradiotherapy, IDH-1 R132H mutations and lower levels of fibrinogen were associated with favorable outcomes. Multivariate analysis proved that chemoradiotherapy, IDH-1 R132H and fibrinogen were independent prognostic factors. In conclusion, plasma fibrinogen could predict clinical outcome and molecular subtype in GBMs., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Objective: To report the clinical and pathological features of primary proximal epithelioid sarcoma (PES) in skull base. Methods: The clinical and pathological features of four cases of PES in skull base from Sanbo Brain Institute of Capital Medical University and Kunming Sanbo Brain Institute were analysed retrospectively. Results: Three cases was female, and one male, the age ranged from 46 to 52 years.All cases occurred in skull base, and sellar region was the main site of involvement.Under the microscope, the tumor cells characterized by epithelioid cell changes, with or without rhabdoid tumor cells.Mitotic figure was active.Immunohistochemical staining showed that AE1/AE3, EMA and CD34 were variously expression in tumor cells.INI-1 protein was lost in all cases.Three cases were detected by FISH, and INI 1 (22q11.2) gene locus was absent in them.Three patients died less than 3 months after surgery, and case 4 was under treatment after five months of surgery. Conclusions: Primary PES in skull base mostly occurs in sellar region and its clinical prognosis is poor.It features with epithelioid/rhabdoid tumor cells with lack granuloma structure as distal ES.It has epithelial and mesenchymal differentiation characteristics.CD34 is always positive. INI 1 gene deletion and protein loss expression are characteristic molecular alteration of PES.

Background: Lower respiratory tract illness is a major cause of morbidity and mortality in children worldwide, however, information about the epidemiological and clinical characteristics of LRTIs caused by HMPV and HBoV in China is limited., Objectives: Human bocavirus (HBoV) and human metapneumovirus (HMPV) are two important viruses for children with lower respiratory tract infections (LRTI). We aimed to assay the correlation between viral load and clinical characteristics of HBoV and HMPV with LRTI in Changsha, China., Methods: Nasopharyngeal aspirates (NPAs) from children with LRTI were collected. Real-time PCR was used to screen HBoV and HMPV. Analyses were performed using SPSS 16.0 software., Results: Pneumonia was the most frequent diagnosis. There was no significant difference between HBoV- and HMPV-positive patients in age (P = .506) or hospitalization duration (P = .280); 24.1% and 18.2% were positive for HBoV and HMPV. HBoV infections peaked in summer (32.2%), and HMPV infections peaked in winter (28.9%). The HBoV-positive patients had a shorter hospitalization duration than the HBoV-negative patients (P = .021), and the HMPV-positive patients had a higher prevalence of fever than the HMPV-negative patients (P = .002). The HBoV viral load was significantly higher among patients aged <1 year (P = .006). The mean HBoV and HMPV viral loads were not significantly different between patients with single infections and coinfections. Patients infected with HBoV only were older than those coinfected with HBoV and other respiratory viruses (P = .005). No significant difference was found in the clinical characteristics of patients infected with HMPV only and those coinfected with HMPV and other respiratory viruses., Conclusion: Pneumonia was the most frequent diagnosis caused by HBoV and HMPV. Neither HBoV nor HMPV viral load was correlated with disease severity., (© 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Objective: Newly identified human rhinovirus C (HRV-C) and human bocavirus (HBoV) cannot propagate in vitro in traditional cell culture models; thus obtaining knowledge about these viruses and developing related vaccines are difficult. Therefore, it is necessary to develop a novel platform for the propagation of these types of viruses., Methods: A platform for culturing human airway epithelia in a three-dimensional (3D) pattern using Matrigel as scaffold was developed. The features of 3D culture were identified by immunochemical staining and transmission electron microscopy. Nucleic acid levels of HRV-C and HBoV in 3D cells at designated time points were quantitated by real-time polymerase chain reaction (PCR). Levels of cytokines, whose secretion was induced by the viruses, were measured by ELISA., Results: Properties of bronchial-like tissues, such as the expression of biomarkers CK5, ZO-1, and PCK, and the development of cilium-like protuberances indicative of the human respiration tract, were observed in 3D-cultured human airway epithelial (HAE) cultures, but not in monolayer-cultured cells. Nucleic acid levels of HRV-C and HBoV and levels of virus-induced cytokines were also measured using the 3D culture system., Conclusion: Our data provide a preliminary indication that the 3D culture model of primary epithelia using a Matrigel scaffold in vitro can be used to propagate HRV-C and HBoV., (Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Lanzhou lamb rotavirus vaccine (LLR) is an oral live attenuated vaccine first licensed in China in 2000. To date, > 60 million doses of LLR have been distributed to children. However, very little is known about faecal shedding of LLR in children. Therefore, faecal samples (n = 1,184) were collected from 114 children for 15 days post-vaccination in September-November 2011/2012. Faecal shedding and viral loads were determined by an enzyme immunoassay kit (EIA) and real-time RT-PCR. The complete genome was sequenced and the vaccine strain was isolated by culture in MA104 cells. Approximately 14.0% (16/114) of children had rotavirus-positive samples by EIA for at least 1 day post-vaccination. Viral loads in EIA-positive samples ranged from < 1.0 × 10 3 to 1.9 × 10 8 copies/g. Faecal shedding occurred as early as post-vaccination day 2 and as late as post-vaccination day 13 and peaked on post-vaccination day 5-10. One LLR strain was isolated by culture in MA104 cells. Sequence analysis showed 99% identity with LLR prototype strain. Faecal shedding of LLR in stool is common within 15 days of LLR vaccination, indicating vaccine strains can replicate in human enteric tissues.

Wenzhou mammarenavirus (WENV) is a novel species of Arenavirus that was first detected in China. We report here a novel WENV variant (WENV G107) from liver samples of Rattus norvegicus that shares 84.7% to 86.8% (large [L] segment) and 84.2% to 87.8% (small [S] segment) nucleotide sequence identity with its closest relative. The genomic characteristics were analyzed based on the whole genome of WENV G107., (Copyright © 2017 Liu et al.)

Objective: To investigate the clinicopathologic characteristics of intractable epilepsy. Methods: Based on the classification criteria proposed by the International League Against Epilepsy (ILAE), a retrospective analysis of the pathological characteristics was done in 822 patients who underwent epilepsy surgery in Sanbo Brain Hospital, Capital Medical University, from June 2008 to December 2012. Results: The mean age of epilepsy onset was 9.9 years, mean duration of epilepsy was 11.9 years. Complex partial seizures were the main presenting features. Histopathological study showed 33 cases (4.01%) with mild forms of cortical malformations, 690 cases (83.94%) with focal cortical dysplasia (FCD) and 99 cases with others (including 39 pure hippocampal sclerosis, 20 cystosclerosis, 19 Sturge-Weber syndrome, 8 tuberous sclerosis complex, 6 without significant pathological changes, 5 gyral malformations and 2 hamartoma). Among the 690 FCD cases, 106 were FCD typeⅠ, 91 were FCD typeⅡ and 493 were FCDⅢ(Ⅲa: 160, Ⅲb: 106, Ⅲc: 26 and Ⅲd: 201). Conclusions: FCDⅢd is the most common histopathological subtype causing intractable epilepsy, mainly due to focal hypoxia/ischemia in the perinatal period, which results in scarring of local brain tissue; this is followed by other isolated forms of FCD (FCDⅠand FCDⅡ), and then FCD Ⅲa and FCD Ⅲb. The reason to distinguish isolated forms of FCD (types Ⅰ and Ⅱ) from FCD Ⅲ and to subclassify FCD Ⅲ is to allow better definition of cortical dyslamination. Therefore, the pathogenic factors of intractable epilepsy can be grouped in greater details, and facilitate the diagnosis and potential curative treatment of intractable epilepsy.

Rhinovirus C (RV-C), a newly identified group of human rhinoviruses (RVs), is associated with exacerbation of severe asthma. The type I interferon (IFN) response induced by this virus and the mechanisms of evasion of IFN-mediated innate immunity for RV-C remain unclear. In this study, we constructed a full-length cDNA clone of RV-C (LZ651) from a clinical sample. IFN-β mRNA and protein levels were not elevated in differentiated Human bronchial epithelial (HBE) cells at the air-liquid interface infected with RV-C, except in the early stage of infection. The ability to attenuate IFN-β activation was ascribed to 3C pro of RV-C, and the 40-His site of 3C pro played an important role. Furthermore, RIG-I was degraded by 3C pro in a caspase-dependent manner and 3C pro cleaved MAVS at 148 Q/A, which inhibited IFN signaling. Taken together, our results demonstrate the mechanism by which RV-C circumvents the production of type I IFN in infected cells., (Copyright © 2017. Published by Elsevier Inc.)