Hemorrhagic fever with renal syndrome (HFRS), a significant rodent-borne disease in Eurasia, particularly in China, can lead to acute kidney injury, coagulation abnormalities, and even death. Co-infection with other pathogens typically exacerbates and complicates this disease. In this study, through metagenomic analysis, we identified the co-infection with human parvovirus B19 (PV B19) in a 41-year-old man with HFRS and no other underlying disease. In addition to typical HFRS symptoms, he exhibited a longer duration of renal injury than other patients with HFRS, along with a persistent decrease in erythrocytes and hemoglobin. The complete PV B19 genome was amplified and showed 86.6–99.7% nucleotide identity and 94.0–100.0% amino acid identity to known PV B19 strains. Phylogenetic analysis revealed that the newly identified PV B19 strain clustered with genotype 1a and had the closest relationship with strain HZ1/China-HZ from Zhejiang Province, China. This study emphasizes that routine screening for PV B19 co-infection in patients with HFRS is essential, particularly in cases with a prolonged course, and persistent decreases in erythrocytes and hemoglobin.

Resveratrol-loaded nanoparticles (RES-NPs) have been found to reduce enterovirus 71 (EV71) replication in EV71-infected-rhabdosarcoma (RD) cells. However, the specific mechanism by which RES-NPs prevent EV71 infection in RD cells remains largely unclear. The cell viability, inflammatory response, and oxidative stress in EV71-infected RD cells were assessed. Inhibition of protein kinase RNA-like endoplasmic reticulum kinase (PERK) significantly increased the viability of infected RD cells, reduced inflammation and oxidative stress, and led to a significant decrease in EV71 mRNA levels. Furthermore, treatment of infected RD cells with RES-NPs significantly increased cell viability and alleviated inflammation and oxidative stress, and these effects were further enhanced by inhibition of PERK. RES-NP treatment also resulted in a decrease in phosphorylated PERK, phosphorylated eukaryotic translation initiation factor 2α (eIF2α), and activating transcription factor 4 (ATF4) levels in infected RD cells, and the levels of these protein were further reduced by treatment with the PERK inhibitor. RES-NPs were found to inhibit EV71 infection by reducing virus-induced inflammatory responses and oxidative stress in RD cells, possibly through inactivation of the PERK-eIF2α-ATF4 signaling pathway.

PURPOSE:Autosomal dominant polycystic kidney disease (ADPKD) is the most common cause of end-stage kidney disease. It has been shown that Acyl-CoA thioesterase 13 (ACOT13) level was reduced in renal cystic tissues from ADPKD patients. However, the role of ACOT13 in ADPKD remains largely elusive. METHODS:The data in the GSE7869 dataset were acquired from the GEO database to determine ACOT13 level between normal renal cortical tissues and renal cystic tissues. Next, the potential functions of ACOT13 were explored by gene set enrichment analysis (GSEA). Furthermore, ACOT13 level in ADPKD cells (WT9-12) was verified by RT-qPCR. The effects of ACOT13 on WT9-12 cell growth were evaluated using the EdU staining and flow cytometry assays. RESULTS:Compared to normal group, ACOT13 mRNA level was obviously reduced in renal cystic tissues and WT9-12 cells. Meanwhile, GSEA results showed that compared to the low ACOT13 expression group, PI3K-Akt and MAPK signaling pathways were inactivated, and PPAR signaling pathway and fatty acid metabolism were activated in high ACOT13 expression group. Furthermore, overexpression of ACOT13 notably reduced WT9-12 cell proliferation and triggered cell cycle arrest. Moreover, ACOT13 overexpression remarkably triggered apoptosis, increased cleaved caspase 3 protein level, reduced ATP production and induced loss of mitochondrial membrane potential in WT9-12 cells, suggesting that ACOT13 overexpression could trigger mitochondrial-related apoptosis in WT9-12 cells. CONCLUSIONS:Collectively, our results showed that overexpression of ACOT13 could suppress WT9-12 cell proliferation and trigger mitochondrial-mediated cell apoptosis, suggesting that ACOT13 may exert a protective role in ADPKD.

BackgroundWhen individuals infected with human immunodeficiency virus (HIV) experience pulmonary infections, they often exhibit severe symptoms and face a grim prognosis. Consequently, early, rapid, and accurate pathogen diagnosis is vital for informing effective treatment strategies. This study aimed to use metagenomic next-generation sequencing (mNGS) and targeted mNGS (tNGS) to elucidate the characteristics of pulmonary infections in HIV and non-HIV individuals.MethodsThis study enrolled 90 patients with pulmonary infection at the Department of Infectious Diseases of The First Hospital of Jilin University from June 2022 to May 2023, and they were divided into HIV (n=46) and non-HIV (n=44) infection groups. Their bronchoalveolar lavage fluid (BALF) was collected for mNGS analysis to evaluate the differences in pulmonary infection pathogens, and tNGS detection was performed on BALF samples from 15 HIV-infected patients.ResultsA total of 37 pathogens were identified in this study, including 21 bacteria, 5 fungi, 5 viruses, 5 mycobacteria, and 1 mycoplasma. The sensitivity of mNGS was 78.9% (71/90), which is significantly higher than that of conventional methods (CTM) (39/90, P=1.5E-8). The combination of mNGS with CTM can greatly enhance the sensitivity of pathogen detection. The prevalence of Pneumocystis jirovecii (82.6% vs. 9.1%), cytomegalovirus (CMV) (58.7% vs. 0%), and Epstein-Barr virus (EBV) (17.4% vs. 2.3%) was significantly higher in the HIV infection group than in the non-HIV infection group (P<0.05). Although no statistically significant difference was observed, the detection rate of Mycobacteria was higher in HIV-infected patients (17.4%) than in the non-HIV group (6.8%). Furthermore, the tNGS results of BALF from 15 HIV-infected patients were not entirely consistent with the mNGS results., and the concordance rate of tNGS for the detection of main pathogens reached 86.7% (13/15).ConclusionNext-generation sequencing (NGS) can accurately detect pathogens in the BALF of patients with pulmonary infection. The sensitivity of tNGS is comparable to that of mNGS. Therefore, this technique should be promoted in the clinic for better patient outcomes.

This study aimed to analyze the clinical significance of serum ferritin, procalcitonin (PCT), and C-reactive protein (CRP) in patients with hemorrhagic fever with renal syndrome (HFRS). The demographical, clinical, and laboratory data of 373 patients with HFRS in northeastern China were retrospectively analyzed. The levels of serum ferritin and PCT in severe patients (n = 108) were significantly higher than those in mild patients (n = 265, p < 0.001) and associated with HFRS severity. The area under the receiver operating characteristic curve (AUC) values of serum ferritin and PCT for predicting the severity of HFRS were 0.732 (95% CI 0.678-0.786, p < 0.001) and 0.824 (95% CI 0.773-0.875, p < 0.001), respectively, showing sensitivity and specificity of 0.75 and 0.88 for serum ferritin, and 0.76 and 0.60 for PCT. The CRP level in HFRS with bacterial co-infection (n = 115) was higher than that without bacterial co-infection (n = 258, p < 0.001). The AUC value of CRP for predicting bacterial co-infection was 0.588 (95% CI 0.525-0.652, p < 0.001), showing sensitivity and specificity of 0.43 and 0.76, respectively. The serum ferritin level in non-survivors (n = 14) was significantly higher than in survivors (n = 359, p < 0.001). The AUC value of serum ferritin for predicting mortality was 0.853 (95% CI 0.774-0.933, p < 0.001), showing sensitivity and specificity of 0.933 and 0.739. Serum ferritin and PCT have a robust association with HFRS severity and mortality, which may be promising predictors, and CRP is an effective biomarker to assess bacterial co-infection in HFRS.

Background Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic kidney disorder. Half of the patients would slowly progress to end-stage renal disease. However, the potential target for ADPKD treatment is still lacking. Methods Four ADPKD patients and two healthy family members were included in this study. The peripheral blood samples were obtained and tested by the whole exome sequencing (WES). The autosomal mutations in ADPKD patients were retained as candidate sites. The Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction network (PPI) analyses were performed by clusterProfiler R package. A dataset containing 18 ADPKD patients and three normal samples were downloaded from the Gene Expression Omnibus (GEO) database and analyzed using the limma R package. Results A total of six mutant genes were identified based on the dominant genetic pattern and most of them had not been reported to be associated with ADPKD. Furthermore, 19 harmful genes were selected according to the harmfulness of mutation. GO and KEGG enrichment analyses showed that the processes of single-organism cellular process, response to stimulus, plasma membrane, cell periphery, and anion binding as well as cyclic adenosine monophosphate (cAMP) signaling pathway and pathways in cancer were significantly enriched. Through integrating PPI and gene expression analyses, acyl-CoA thioesterase 13 (ACOT13), which has not been reported to be related to ADPKD, and prostaglandin E receptor 2 (PTGER2) were identified as potential genes associated with ADPKD. Conclusions Through combination of WES, gene expression, and PPI network analyses, we identified ACOT13 and PTGER2 as potential ADPKD-related genes.

Background: Actinomycosis is a rare cause of unexplained origin fever (FUO). The NGS, particularly in cases of FUO in conventional microbiology, is a promising and advantageous technology for earlier diagnosis and more success. It gives new insights in the management of FUO, especially in infectious diseases.Case presentation: We present a case of a 71-year-old woman who had FUO that the etiology was endobronchial actinomycosis eventually diagnosed by next-generation sequencing of bronchoalveolar lavage fluid. She was admitted to the our department with intermittent fever up to 40.0℃, chills, cough with white sputum, chest distress and slightly dyspnea over one month. According to special clinical course and laboratory data of the patient, she was given intravenous sulbenicillin sodium for 11 days and oral amoxicillin at 500 mg every 8 h for another 1 month. When she returned for follow-up, she reported a notable improvement in her cough, dyspnea, sputum production and fever that was completely absent.Conclusion: In obscure causes of FUO, clinicians should consider the possibility of thoracic actinomycosis and actively use next-generation sequencing to help diagnose.

Eight members of a big family with laboratory-confirmed COVID-19 pneumonia were admitted to First Hospital of Jilin University, Changchun, China, from 28 January to 5 February 2020. The clinical records, laboratory results, and chest computed tomography (CT) scans were retrospectively reviewed. Throat swab samples were positive for severe acute respiratory syndrome coronavirus 2, confirmed by the Center for Disease Control and Prevention of Changchun. All eight patients had fever of different degrees; and 6, 3, and 2 had cough; diarrhea; and sore throat. With disease progression, the percentage of lymphocytes in older patients increased, CT images worsened, and the ratio of lymphocytes increased when images revealed inflammation absorption. Although the CT images showed ground-glass opacities in the youngest patient, his lymphocyte count did not decrease with mild clinical symptoms, and the images showed that inflammation was quickly absorbed. Only the oldest patient developed critical illness. The C reaction protein (CRP) levels of Patient 5 increased significantly, and the rate of decline was the slowest, while his condition was the most severe. The clinical manifestations of COVID-19 in this family cluster varied with contact, age, and underlying disease. Lymphocyte count and quality of chest CT images appeared inversely associated with disease severity. CRP changes may be an indicator of disease severity and prognosis.

Since its outbreak in Wuhan, Hubei Province China, 2019-coronavirus infected disease (COVID-19) had been widely spread all over the world, the control of which calls for a better understanding of its epidemiology and clinical characteristics. We included 12 confirmed cases of COVID-19 in First Affiliated Hospital of Jilin University from 23 January 2020 to 11 February 2020, which were retrospectively analyzed for epidemiological, demographic, clinical, laboratory, and radiological features. All the patients were confirmed by nucleic acid detection, the average age of whom was 45.25 years (range, 23–79 years). Most patients had a history of Wuhan traveling or had contact with Wuhan travelers or infected cases. Obvious family cluster was observed. Clinical manifestations included fever (12/12), fatigue (10/12), cough (6/12), sore throat (4/12), headache (3/12), and diarrhea (2/12). Only three out of eight patients had pneumonia manifestation on radiography. Most patients had a normal white blood cell (WBC) count and normal or reduced lymphocyte (LY) count. Pneumonia changes were observed in all the four patients who underwent a chest CT scan. Only one elderly patient developed severe pneumonia, while all the rest were mild disease and had a self-limiting course.

Background: Coronavirus disease 2019 has become a major problem for the world. We reported a representative case with thrombocytopenia. Case report: A 44-year-old female patient sought medical attention for fatigue and cough of 1 day duration. Thirteen days before disease onset, the patient had returned from Hubei province. Her body temperature on admission was 38.6℃. Blood routine test showed a white blood cell count of 4.0×10 9 /L, lymphocyte count of 1×10 9 /L, platelet count of 118×10 9 /L, and C-reactive protein of 6.0mg/L. Lung computed tomography (CT) scan showed: large patches of ground-glass opacities at the posterior segment of the right upper lung lobe and bilaterally at the basal segment of the lower lung lobes. Her throat swabs tested positive for novel coronavirus nucleic acid. After antiviral and symptomatic treatment were given, on day 5 of hospitalization, her symptoms of coughing and chest pain worsened after coughing, and she also developed hemoptysis. Repeated lung CT scans showed that the lesion area had increased. The lymphocyte count had decreased to 0.55×10 9 /L and the platelet count had decreased to 9×10 9 /L on day 6. After a series of multimodal therapies were carried out, the patient’s platelet and lymphocyte count gradually increased to normal. Conclusion: We reported a COVID-2019 case with significant thrombocytopenia, which was more significantly decreased than in normal viral infections. However, the mechanism of thrombocytopenia is unknown and requires further research.

Background The clinical characteristics of patients with confirmed 2019 novel coronavirus disease (COVID-19) in Jilin Province, China were investigated. Methods Clinical, laboratory, radiology, and treatment data of 41 hospitalized patients with confirmed COVID-19 were retrospectively collected. The population was stratified by disease severity as mild, moderate, or severe, based on guidelines of the National Health and Medical Commission of China. Results The 41 hospitalized patients with COVID-19 were studied, and the median age was 45 years (interquartile range [IQR], 31–53; range, 10–87 years) and 18 patients (43.9%) were female. All of the patients had recently visited Wuhan or other places (ie, Beijing, Thailand) or had Wuhan-related exposure. Common symptoms included fever (32[78%]) and cough (29[70.7%]). All patients were without hepatitis B/C virus hepatitis. CRP (C-reactive protein, 11.3 mg/L [interquartile range {IQR}, 2.45–35.2]) was elevated in 22 patients (53.7%), and cardiac troponin I (1.5 ng/mL [IQR, 0.8–5.0]) was elevated in 41 patients (100%). Chest computed tomographic scans showed bilateral ground glass opacity (GGO) or GGO with consolidation in the lungs of 27(65.9%) patients. 31(75.6%) patients had an abnormal electrocardiograph (ECG). Comparing the three groups, the levels of CRP and cardiac troponin I, GGO distribution in bilateral lungs, and electrocardiogram changes were statistically significant ( p < 0.05). Cardiac troponin I had a strong positive correlation with CRP (r = 0.704, p = 0.042) and LDH (r = 0.738, p = 0.037). Conclusion Significant differences among the groups suggest that several clinical parameters may serve as biomarkers of COVID-19 severity at hospital admission. Elevated cTnI could be considered as a predictor of severe COVID-19, reflecting the prognosis of patients with severe COVID-19. The results warrant further inspection and confirmation.

TGF-β signal pathway activation is vital in the pathogenesis of DKD. We aim to investigate the role of Yishenhuoxue formula on TGF-β/Smad signal transduction in DKD rats. 60 male adult Wistar rats were enrolled and randomly allocated into four groups: N group, M group (given STZ 60mg/kg, ip), H group (given Yishenhuoxue formula 1.0g/kg/day, ig) and L group (given Yishenhuoxue formula 0.5g/kg/day, ig). The levels of BW, 24h UV, SCr, UCr, mALB were measured after 8 weeks treatment, while the levels of KW/BW index, CCr and UAER were calculated by relevant formula. The rats' left kidneys were harvested to detect histological changes by PAS staining and right kidneys were harvested to detect the levels of TGF-β, Smad2/3, phosphorylated Smad 2/3, Smad 7 and CTGF by western blot analysis. We found that Yishenhuoxue formula treatment can protect kidneys from DKD injury, which is illustrated with following criteria: 1) a significant decrement in KW/BW index, 24h UV, SCr, mALB and UAER, while a significant increment in BW, UCr, CCr (p<0.05 vs. M group); 2) minor and segmental changes as slight expansion of the glomerular basement membrane compared with M group; 3) an apparent decrease in levels of TGF-β1, phosphorylated Smad 2/3 and CTGF, while an apparent increase in levels of Smad 2/3 and Smad7 compared with M group (p<0.05). The studies confirm that Yishenhuoxue formula has strong inhibitory effect on TGF-β/Smad signal transduction in DKD rats' kidneys by decreasing expression of TGF-β1, weakening of Smad 2/3 phosphorylation and increasing expression of Smad 7.

BACKGROUND:Hand, foot, and mouth disease (HFMD) is a self-limited disease caused mainly by enterovirus 71 and coxsackievirus A16; however, some cases have severe neurological complications, pulmonary edema, and fetal death. In this study, we analyzed the changes in natural killer (NK) cell subsets, their receptors, and serum inflammatory cytokines in children with HFMD.METHODS:Peripheral blood samples were collected from 70 HFMD pediatric patients admitted Department of Infectious Diseases of our hospital from July 2016 to November 2017 and from 16 healthy children receiving physical examination in the disease control and prevention center as the healthy control group. The changes in three NK cell subsets and their receptors, and serum inflammatory cytokines were detected via flow cytometry.RESULTS:The distribution of CD3-CD16+CD56+ and CD3-CD16+CD56- NK cell subsets in the HFMD group increased significantly compared with that in the healthy control group, while CD3-CD16-CD56+ NK cell subset showed no significant difference in the two groups. Besides, the distribution of the CD3-CD16+CD56+ NK cell subset was significantly higher than the CD3-CD16+CD56- NK cell subset. The distribution of the NKG2A receptor on the CD3-CD16+CD56+ NK cell subset in the HFMD group was significantly higher than that in the healthy control group. Moreover, the serum levels of IL-17A, IL-10, IL-6, and IL-2 in the HFMD group were higher than those in the healthy control group.CONCLUSIONS:The results showed that the positive distribution of NKG2A in the NK cell subset and the content of inflammatory cytokines could be of diagnostic value for early detection of HFMD in patients and prediction of the severity of the disease.

A number of studies have demonstrated that resveratrol (RES) has a variety of biological functions, including cardiovascular protective effects, treatment of mutations, and anti‐inflammatory, anti‐tumor and antiviral effects. In the present study, RES-loaded nanoparticles (RES-NPs) were used to protect rhabdosarcoma (Rd) cells from enterovirus 71 (EV71) infection, and the relevant mechanisms were also explored. An amphiphilic copolymer, monomethoxy poly (ethylene glycol)-b-poly (d,L-lactide), was used as vehicle material, and RES-NPs with necessitated drug-loading content and suitable sizes were prepared under optimized conditions. RES-NPs exhibited the ability to inhibit the increase of intracellular oxidative stress. The prospective mechanism for the function of RES-NPs suggested was that RES-NPs may inhibit the oxidative stress-mediated PERK/eIF2α/ATF4 signaling pathway, downregulate the autophagy pathway and resist EV71-induced Rd cells injury. Furthermore, RES-NPs treatment markedly inhibited the secretion of inflammatory factors, including interleukin (IL)-6, IL-8 and tumor necrosis factor-α elicited by EV71 infection. concomitantly, inhibitors of oxidative stress, endoplasmic reticulum stress (ERS) or autophagy were demonstrated to negate the anti-inflammatory and antiviral effects of RES-NPs on EV71-infected Rd cells. These results demonstrated that RES-NPs attenuated EV71-induced viral replication and inflammatory effects by inhibiting the oxidative stress-mediated ERS/autophagy signaling pathway. In view of their safety and efficiency, these RES‐NPs have potential applications in protecting Rd cells from EV71 injury. Introduction Enteroviruses are a group of small single-strand, positive-sense RNA viruses in the Enterovirus genus of the Picornaviridae family (1-3). Infection with certain enteroviruses, including enterovirus 71 (EV71) and coxsackievirus B, lead to severe diseases including aseptic meningitis, brainstem encephalitis, myocarditis and pancreatitis (4,5). Enterovirus infections are particularly common among children <5 years old, and it is one of the major causative pathogens of hand, foot and mouth disease (HFMd), which affects millions of children in the Asia‐Pacific region (6,7). In 2015, there were up to 2 million patients with HFMd, with 129 mortalities reported in china. The clinical presentation of HFMd is characterized by buccal ulcerative lesions with pain, and skin rashes on hands and feet without pain (8). A small number of children may exhibit central nervous system and respiratory system damage, causing aseptic meningitis, encephalitis, acute flaccid paralysis, neurogenic pulmonary edema and myocarditis. critically ill children progress rapidly, and are at risk of mortality (9). In recent years, there have been a number of treatments for EV infection, including vaccines, antivirals and interferon (10,11). Unfortunately, the efficacy of these treatments is not satisfactory. The primary active ingredient of Polygonum cuspidatum is polydatin and resveratrol (RES) (12). Polydatin has exhibited antitussive, hepatoprotective and anti-shock effects, and the ability to inhibit platelet aggregation, among other effects (13). RES is the most valuable and promising ingredient in P. cuspidatum, and it has antibacterial, anti‐inflammatory, anti-allergic, anti-thrombotic, anti-oxidant, anti-cancer and anti-mutation effects (14-16). In addition, RES also has antiviral effects against certain viruses, including influenza virus, hepatitis c virus, respiratory syncytial virus, Epstein-Barr virus, African swine fever virus, enterovirus and duck enteritis virus (17-18). However, the solubility of RES is poor in aqueous solution, and it is easily degraded (12,14). Therefore, RES has a low bioavailability, which results in a limited curative effect. Nanoparticle (NP) technology may improve the solubility and therapeutic effects of hydrophobic drugs (19-21). In the present study, in order to effectively inhibit the replication of EV71 virus, RES-loaded nanoparticles (RES-NPs) were used, and the protective mechanism of RES-NPs against rhabdosarcoma (Rd) cells infected with EV71 was investigated. Resveratrol‐loaded nanoparticles inhibit enterovirus 71 replication through the oxidative stress‐mediated ERS/autophagy pathway NA dU, XIAO-HUA LI, WAN-GUO BAO, BIN WANG, GUANG XU and FENG WANG department of Infectious diseases, The First Hospital of Jilin University, changchun, Jilin 130021, P.R. china Received October 19, 2018; Accepted May 23, 2019 dOI: 10.3892/ijmm.2019.4211 Correspondence to: Professor Feng Wang, department of Infectious diseases, The First Hospital of Jilin University, 71 Xinmin Street, changchun, Jilin 130021, P.R. china E-mail: wangfeng3077@163.com

Gene expression and DNA methylation levels affect the outcomes of patients with cancer. The present study aimed to establish a multigene risk model for predicting the outcomes of patients with cervical cancer (CerC) treated with or without radiotherapy. RNA sequencing training data with matched DNA methylation profiles were downloaded from The Cancer Genome Atlas database. Patients were divided into radiotherapy and non‑radiotherapy groups according to the treatment strategy. Differently expressed and methylated genes between the two groups were identified, and 8 prognostic genes were identified using Cox regression analysis. The optimized risk model based on the 8‑gene signature was defined using the Cox's proportional hazards model. Kaplan‑Meier survival analysis indicated that patients with higher risk scores exhibited poorer survival compared with patients with lower risk scores (log‑rank test, P=3.22x10‑7). Validation using the GSE44001 gene set demonstrated that patients in the high‑risk group exhibited a shorter survival time comprared with the low‑risk group (log‑rank test, P=3.01x10‑3). The area under the receiver operating characteristic curve values for the training and validation sets were 0.951 and 0.929, respectively. Cox regression analyses indicated that recurrence and risk status were risk factors for poor outcomes in patients with CerC treated with or without radiotherapy. The present study defined that the 8‑gene signature was an independent risk factor for the prognosis of patients with CerC. The 8‑gene prognostic model had predictive power for CerC prognosis.

BACKGROUND:The SK-PN-DW cell line was established in 1979 and is commercially available. Despite the use of this cell line as an in vitro model for functional and therapeutic studies of malignant primitive neuroectodermal tumor (PNET), there is a lack of complete information about the genetic alterations that are present at the cytogenetic level. Thus, the current study aimed to characterize the cytogenetic profile of this cell line.METHODS:Routine G-banded chromosome analysis, fluorescence in situ hybridization, and oligonucleotide array comparative genomic hybridization assays were performed to characterize the chromosomal changes in this cell line.RESULTS:The G-banded karyotype analysis showed that the number of chromosomes in this cell line ranged between 36 and 41. Importantly, all cells displayed a loss of chromosomes Y, 11, 13, and 18. However, some cells showed an additional loss of chromosome 10. Additionally, the observed structural changes indicated: a) unbalanced translocation between chromosomes 1 and 7; b) translocation between chromosomes 11 and 22 at breakpoints 11q24 and 22q12, which is a classical translocation that is associated with Ewing sarcoma; c) a derivative chromosome due to a whole arm translocation between chromosomes 16 and 17 at likely breakpoints 16p10 and 17q10; and d) possible rearrangement in the short arm of chromosome 18. Moreover, a variable number of double minutes were also observed in each metaphase cell. Furthermore, the microarray assay results not only demonstrated genomic-wide chromosomal imbalance in this cell line and precisely placed chromosomal breakpoints on unbalanced, rearranged chromosomes, but also revealed information about subtle chromosomal changes and the chromosomal origin of double minutes. Finally, the fluorescence in situ hybridization assay confirmed the findings of the routine cytogenetic analysis and microarrays.CONCLUSION:The accurate determination of the cytogenetic profile of the SK-PN-DW cell line is helpful in enabling the research community to utilize this cell line for future identity and comparability studies, in addition to demonstrating the utility of the complete cytogenetic profile, as a public resource.

OBJECTIVES:To determine blood Brucella DNA loads between brucellosis patients and those without brucellosis.METHODS:The patient group included 350 brucellosis patients. The control was composed of 200 subjects without brucellosis. The extracted DNA from blood was tested by quantitative polymerase chain reaction (qPCR). The cutoff value was determined by receiver operating characteristic curve analysis. A portion of the brucellosis patients were monitored by qPCR during therapy.RESULTS:The detection limit of qPCR was between 1E+01cfu/μL and 1E+08cfu/μL. The standard curve R2 reached 0.998. The cutoff value was 4E+01cfu/μL, which was determined by comparison of the patient group and the control. The qPCR assay had a specificity of 100% and a sensitivity of 93.14%. The monitoring results showed that the Brucella DNA load decreased in most patients during the first 4 weeks of treatment. One patient with bad treatment compliance showed a rebound.CONCLUSIONS:The qPCR results were in accordance with the course of brucellosis in the clinic. The DNA load often reflects the situation of the Brucella-infected patient. The cutoff value provides an important reference of infection. This qPCR-based method can be used to assist in the diagnosis of brucellosis and to adjust the therapy.

A number of studies have demonstrated that resveratrol (RES) has a variety of biological functions, including cardiovascular protective effects, treatment of mutations, and anti-inflammatory, anti-tumor and antiviral effects. In the present study, RES-loaded nanoparticles (RES-NPs) were used to protect rhabdosarcoma (RD) cells from enterovirus 71 (EV71) infection, and the relevant mechanisms were also explored. An amphiphilic copolymer, monomethoxy poly (ethylene glycol)-b-poly (D,L-lactide), was used as vehicle material, and RES-NPs with necessitated drug-loading content and suitable sizes were prepared under optimized conditions. RES-NPs exhibited the ability to inhibit the increase of intracellular oxida-tive stress. The prospective mechanism for the function of RES-NPs suggested was that RES-NPs may inhibit the oxidative stress-mediated PERK/eIF2 alpha/ATF4 signaling pathway, downregulate the autophagy pathway and resist EV71-induced RD cells injury. Furthermore, RES-NPs treatment markedly inhibited the secretion of inflammatory factors, including interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha elicited by EV71 infection. Concomitantly, inhibitors of oxidative stress, endoplasmic reticulum stress (ERS) or autophagy were demonstrated to negate the anti-inflammatory and antiviral effects of RES-NPs on EV71-infected RD cells. These results demonstrated that RES-NPs attenuated EV71-induced viral replication and inflammatory effects by inhibiting the oxidative stress-mediated ERS/autophagy signaling pathway. In view of their safety and efficiency, these RES-NPs have potential applications in protecting RD cells from EV71 injury.

Introduction Anti-oxidative stress and inhibition of TGF-β1/Smads signaling cascade are essential therapeutic strategies for diabetic nephropathy (DN). In this study, we aimed to explore the effect of combination of Ginsenoside Rg1 and Astragaloside IV on oxidative stress and TGF-β1/Smads signaling in DN rats. Materials and methods Wistar rats were divided into five groups: N group, M group (streptozotocin [STZ], intraperitoneally), G group (STZ rats with Ginsenoside Rg1, intragastrically [ig]), A group (STZ rats with Astragaloside IV, ig) and C group (STZ rats with Ginsenoside Rg1 and Astragaloside IV, ig). The levels of methane dicarboxylic aldehyde (MDA), catalase (CAT), glutathione peroxidase (GSH-PX), total anti-oxidative capacity (T-AOC), blood urea nitrogen (BUN), β2-microglobulin (β2-MG), serum creatinine (SCr) and urinary creatinine (UCr) were detected in all the groups. The left kidneys of the rats were harvested to detect the expression of TGF-β1, Smad2/3, Smad7 and CTGF by immunohistochemical staining, while the right kidneys were used to detect the mRNA expression of TGF-β1, Smad7 and CTGF by real-time PCR. Results Rats in G group, A group and C group had lower level of MDA but higher levels of CAT, GSH-PX and T-AOC compared with rats in M group. Rats in C group showed the best anti-oxidative stress level. G group, A group and C group treatments significantly decreased the levels of BUN, SCr, β2-MG and UCr. In addition, C group treatment showed the best kidney protective effect. G group, A group and C group treatments significantly diminish ED both factor and mRNA overexpression of TGF-β1 and CTGF but increase Smad7 expression in kidney tissue. Conclusion The combination of Ginsenoside Rg1 and Astragaloside IV may potentially protect against DN by reducing oxidative stress and inhibiting TGF-β1/Smads signaling cascade.

Background. Hantaan virus infection causes lethal hemorrhagic fever with renal syndrome (HFRS) in humans. Little is known about how monocytes contribute to HFRS pathogenesis. In this study, we aimed to investigate changes in various monocyte subsets in HFRS patients. Methods: A total of 41 HFRS patients and 17 age-, sex-, and ethnicity-matched healthy control subjects were included in this study. Numbers/percentages of various monocyte subsets were quantitatively determined using flow cytometry. Serum levels of interleukin (IL)-10, IL-12, and tumor necrosis factor alpha (TNF-beta) were detected using a cytometric bead array (CBA). Results: CD14(+) (+)CD16(+) intermediate monocytes were significantly higher in HFRS patients compared to healthy controls (P < 0.01), especially during the acute phase. The expression of both CD163 and CD206 on CD14(+) (+)CD16(+) intermediate monocytes were increased during the acute phase of HFRS (P < 0.01 and P < 0.05, respectively) when comparing the convalescent phase and healthy controls. Furthermore, the numbers of CD14(+) (+)CD16(+) monocytes during the acute phase, and the percentages of CD14(+) (+)CD16(+) CD163(+) monocytes in patients with severe/critical HFRS were much higher compared to patients with mild/moderate HFRS. This also positively correlated with increased levels of white blood cells (WBC), blood urea nitrogen (BUN), and creatinine (Cr). However, the percentages of CD14(+) (+)CD16(+)CD206(+) monocytes were higher in mild/moderate HFRS than in severe/critical HFRS, and they negatively correlated with platelets (PLT) and Cr. Conclusions: Higher frequency of the CD14(+) (+)CD16(+) intermediate monocytes and increased expression of CD163 and CD206 markers on CD14(+) (+)CD16(+) monocytes were detected in patients with HFRS. The changes in the frequency of CD14(+) (+)CD16(+) monocytes and expression of CD163 and CD206 markers on CD14(+) (+)CD16(+) monocytes positively correlated with the severity of HFRS.