Metagenomic analysis reveals oropharyngeal microbiota alterations in patients with COVID-19.

COVID-19 remains a serious emerging global health problem, and little is known about the role of oropharynx commensal microbes in infection susceptibility and severity. Here, we present the oropharyngeal microbiota characteristics identified by shotgun metagenomic sequencing analyses of oropharynx swab specimens from 31 COVID-19 patients, 29 influenza B patients, and 28 healthy controls. Our results revealed a distinct oropharyngeal microbiota composition in the COVID-19 patients, characterized by enrichment of opportunistic pathogens such as Veillonella and Megasphaera and depletion of Pseudopropionibacterium, Rothia, and Streptococcus. Based on the relative abundance of the oropharyngeal microbiome, we built a microbial classifier to distinguish COVID-19 patients from flu patients and healthy controls with an AUC of 0.889, in which Veillonella was identified as the most prominent biomarker for COVID-19 group. Several members of the genus Veillonella, especially Veillonella parvula which was highly enriched in the oropharynx of our COVID-19 patients, were also overrepresented in the BALF of COVID-19 patients, indicating that the oral cavity acts as a natural reservoir for pathogens to induce co-infections in the lungs of COVID-19 patients. We also found the increased ratios of Klebsiella sp., Acinetobacter sp., and Serratia sp. were correlated with both disease severity and elevated systemic inflammation markers (neutrophil-lymphocyte ratio, NLR), suggesting that these oropharynx microbiota alterations may impact COVID-19 severity by influencing the inflammatory response. Moreover, the oropharyngeal microbiome of COVID-19 patients exhibited a significant enrichment in amino acid metabolism and xenobiotic biodegradation and metabolism. In addition, all 26 drug classes of antimicrobial resistance genes were detected in the COVID-19 group, and were significantly enriched in critical cases. In conclusion, we found that oropharyngeal microbiota alterations and functional differences were associated with COVID-19 severity.

Multifocal Electroretinogram Can Detect the Abnormal Retinal Change in Early Stage of type2 DM Patients without Apparent Diabetic Retinopathy.

PURPOSE: To study retinal function defects in type 2 diabetic patients without clinically apparent retinopathy using a multifocal electroretinogram (mf-ERG). METHODS: Seventy-six eyes of thirty-eight type 2 diabetes mellitus(DM) patients without clinically apparent retinopathy and sixty-four normal eyes of thirty-two healthy control (HC) participants were examined using mf-ERG. RESULTS: Patients with type 2 DM without apparent diabetic retinopathy demonstrated an obvious implicit time delay of P1 in ring 1, ring 3, and ring 5 compared with healthy controls (t = 5.184, p ≤ 0.001; t = 8.077, p ≤ 0.001; t = 2.000, p = 0.047, respectively). The implicit time (IT) in ring 4 of N1wave was significantly delayed in the DM group (t = 2.327, p = 0.021). Compared with the HC group, the implicit time of the P1 and N1 waves in the temporal retina zone was significantly prolonged (t = 3.66, p ≤ 0.001; t = 2.187, p = 0.03, respectively). And the amplitude of P1 in the temporal retina decreased in the DM group, which had a significantly statistical difference with the healthy controls (t = -6.963, p ≤ 0.001). However, there were no differences in either the amplitude of the response or the implicit time of the nasal retina zone between DM and HC. The AUC of multiparameters of mf-ERG was higher in the diagnosis of DR patients. CONCLUSIONS: Patients with type 2 DM without clinically apparent retinopathy had a delayed implicit time of P1 wave in temporal regions of the postpole of the retina compared with HC subjects. It demonstrates that mf-ERG can detect the abnormal retinal change in the early stage of type2 DM patients without apparent diabetic retinopathy. Multiparameters of mf-ERG can improve the diagnostic efficacy of DR, and it may be a potential clinical biomarker for early diagnosis of DR.

An increased expression of long non-coding RNA PANDAR promotes cell proliferation and inhibits cell apoptosis in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies worldwide. Emerging evidence indicates that aberrantly expressed long non-coding RNAs (lncRNAs) act as imperative roles in tumorigenesis and progression. PANDAR (promoter of CDKN1A antisense DNA damage activated RNA) is a novel lncRNA that contributes to the development of various cancers. However, its clinical significance and potential effects on PDAC remains unknown. In the present study, qRT-PCR was performed to explore the expression levels of PANDAR in PDAC tissues and corresponding non-tumor tissues, the correlation between PANDAR expression and clinicopathological characteristics was also analyzed. The functional roles of lncRNA PANDAR in PDAC cells were evaluated both in vitro and in vivo. The results indicated that PANDAR was aberrantly overexpressed in PDAC tissues and cell lines, and this overexpression was closely associated with tumor stage and vascular invasion in PDAC patients. Besides, silencing of PANDAR exerted tumor suppressive effect via reducing cell proliferation, colony-forming ability, inducing cell cycle G0/G1 arrest and apoptosis in PANC1 and Capan-2 cells. Further in vivo study confirmed the oncogenesis role of PANDAR in PDAC cells. Overall, our findings may help to develop a potential therapeutic target for the patients with PDAC.

Comparative analysis of quinolone resistance in clinical isolates of Klebsiella pneumoniae and Escherichia coli from Chinese children and adults.

The objective of this study was to compare quinolone resistance and gyrA mutations in clinical isolates of Klebsiella pneumoniae and Escherichia coli from Chinese adults who used quinolone in the preceding month and children without any known history of quinolone administration. The antimicrobial susceptibilities of 61 isolates from children and 79 isolates from adults were determined. The mutations in the quinolone resistance-determining regions in gyrA gene were detected by PCR and DNA sequencing. Fluoroquinolone resistance and types of gyrA mutations in isolates from children and adults were compared and statistically analyzed. No significant differences were detected in the resistance rates of ciprofloxacin and levofloxacin between children and adults among isolates of the two species (all P > 0.05). The double mutation Ser83→Leu + Asp87→Asn in the ciprofloxacin-resistant isolates occurred in 73.7% isolates from the children and 67.9% from the adults, respectively (P = 0.5444). Children with no known history of quinolone administration were found to carry fluoroquinolone-resistant Enterobacteriaceae isolates. The occurrence of ciprofloxacin resistance and the major types of gyrA mutations in the isolates from the children were similar to those from adults. The results indicate that precautions should be taken on environmental issues resulting from widespread transmission of quinolone resistance.

[Antioxidant effect of Ganoderma polysaccharide peptide].

AIM: To study the antioxidant effect of Ganoderma polysaccharide peptide (GLPP) and its mechanism. METHODS: Copper was used as oxidant to induce low lipoprotein (LDL) oxidative modification, and alloxan was given i.v. to induce reactive oxygen species (ROS) injury in mice. RESULTS: GLPP decreased oxidation of LDL and the relative electrophoretic mobility (REM) of oxidative product of LDL. After GLPP was given i.p. for 20 days, the concentration of malondialdehyde(MDA) in serum and heart of mice was decreased. The GSHpx enzyme activity was increased, while the SOD level was decreased. The catalase(CAT) levels were not significantly changed by GLPP. CONCLUSION: GLPP showed antioxidant effect by scavenging ROS or enhancing the enzyme activity of GSHpx in vivo and in vitro.

Protective effects of Ganoderma lucidum polysaccharides peptide on injury of macrophages induced by reactive oxygen species.

AIM: To study the protective effects of Ganoderma lucidum polysaccharides peptide (GLPP) on the mice peritoneal macrophages injured by reactive oxygen species (ROS), derived from tert-butylhydroperoxide (tBOOH) in vitro and in vivo. METHODS: Mice peritoneal macrophages were injured by ROS, derived from tBOOH. The survival rate of macrophages was measured by MTT assay, and the morphological changes of macrophages were observed under light and electron microscopes. RESULTS: GLPP (50, 100, 200 mg/kg, ip for 5 d) could inhibit the foam cell formation and necrosis of macrophages. The survival rate of macrophages was increased. GLPP (3.125, 12.5, 50, 200 mg/L) given to the cultured macrophages brought the same protective effects. Under the electron microscope it was found that GLPP (100 mg/kg, ip, for 5 d) could protect the organelle such as mitochondria against injury by tBOOH. CONCLUSION: GLPP had significant scavenging ROS and antioxidant effects.