Epidemiological and etiological characteristics of 1266 patients with severe acute respiratory infection in central China, 2018-2020: a retrospective survey.

BACKGROUND: Severe acute respiratory infection (SARI), a significant global health concern, imposes a substantial disease burden. In China, there is inadequate data concerning the monitoring of respiratory pathogens, particularly bacteria, among patients with SARI. Therefore, this study aims to delineate the demographic, epidemiological, and aetiological characteristics of hospitalised SARI patients in Central China between 2018 and 2020. METHODS: Eligible patients with SARI admitted to the First Affiliated Hospital of Zhengzhou University between 1 January 2018 and 31 December 2020 were included in this retrospective study. Within the first 24 h of admission, respiratory (including sputum, nasal/throat swabs, bronchoalveolar lavage fluid, thoracocentesis fluid, etc.), urine, and peripheral blood specimens were collected for viral and bacterial testing. A multiplex real-time polymerase chain reaction (PCR) diagnostic approach was used to identify human influenza virus, respiratory syncytial virus, parainfluenza virus, adenovirus, human bocavirus, human coronavirus, human metapneumovirus, and rhinovirus. Bacterial cultures of respiratory specimens were performed with a particular focus on pathogenic microorganisms, including S. pneumoniae, S. aureus, K. pneumoniae, P. aeruginosa, Strep A, H. influenzae, A. baumannii, and E. coli. In cases where bacterial culture results were negative, nucleic acid extraction was performed for PCR to assay for the above-mentioned eight bacteria, as well as L. pneumophila and M. pneumoniae. Additionally, urine specimens were exclusively used to detect Legionella antigens. Furthermore, epidemiological, demographic, and clinical data were obtained from electronic medical records. RESULTS: The study encompassed 1266 patients, with a mean age of 54 years, among whom 61.6% (780/1266) were males, 61.4% (778/1266) were farmers, and 88.8% (1124/1266) sought medical treatment in 2020. Moreover, 80.3% (1017/1266) were housed in general wards. The most common respiratory symptoms included fever (86.8%, 1122/1266) and cough (77.8%, 986/1266). Chest imaging anomalies were detected in 62.6% (792/1266) of cases, and 58.1% (736/1266) exhibited at least one respiratory pathogen, with 28.5% (361/1266) having multiple infections. Additionally, 95.7% (1212/1266) of the patients were from Henan Province, with the highest proportion (38.3%, 486/1266) falling in the 61-80 years age bracket, predominantly (79.8%, 1010/1266) seeking medical aid in summer and autumn. Bacterial detection rate (39.0%, 495/1266) was higher than viral detection rate (36.9%, 468/1266), with the primary pathogens being influenza virus (13.8%, 175/1266), K. pneumoniae (10.0%, 127/1266), S. pneumoniae (10.0%, 127/1266), adenovirus (8.2%, 105/1266), P. aeruginosa (8.2%, 105/1266), M. pneumoniae (7.8%, 100/1266), and respiratory syncytial virus (7.7%, 98/1266). During spring and winter, there was a significant prevalence of influenza virus and human coronavirus, contrasting with the dominance of parainfluenza viruses in summer and autumn. Respiratory syncytial virus and rhinovirus exhibited higher prevalence across spring, summer, and winter. P. aeruginosa, K. pneumoniae, and M. pneumoniae were identified at similar rates throughout all seasons without distinct spikes in prevalence. However, S. pneumoniae showed a distinctive pattern with a prevalence that doubled during summer and winter. Moreover, the positive detection rates of various other viruses and bacteria were lower, displaying a comparatively erratic prevalence trend. Among patients admitted to the intensive care unit, the predominant nosocomial bacteria were K. pneumoniae (17.2%, 43/249), A. baumannii (13.6%, 34/249), and P. aeruginosa (12.4%, 31/249). Conversely, in patients from general wards, predominant pathogens included influenza virus (14.8%, 151/1017), S. pneumoniae (10.4%, 106/1017), and adenovirus (9.3%, 95/1017). Additionally, paediatric patients exhibited significantly higher positive detection rates for influenza virus (23.9%, 11/46) and M. pneumoniae (32.6%, 15/46) compared to adults and the elderly. Furthermore, adenovirus (10.0%, 67/669) and rhinovirus (6.4%, 43/669) were the primary pathogens in adults, while K. pneumoniae (11.8%, 65/551) and A. baumannii (7.1%, 39/551) prevailed among the elderly, indicating significant differences among the three age groups. DISCUSSION: In Central China, among patients with SARI, the prevailing viruses included influenza virus, adenovirus, and respiratory syncytial virus. Among bacteria, K. pneumoniae, S. pneumoniae, P. aeruginosa, and M. pneumoniae were frequently identified, with multiple infections being very common. Additionally, there were substantial variations in the pathogen spectrum compositions concerning wards and age groups among patients. Consequently, this study holds promise in offering insights to the government for developing strategies aimed at preventing and managing respiratory infectious diseases effectively.

Alcohol dehydrogenase 1 is a tubular mitophagy-dependent apoptosis inhibitor against septic acute kidney injury.

Alcohol dehydrogenase 1 (ADH1) is an alcohol-oxidizing enzyme with poorlydefined biology. Here we report that ADH1 is highly expressed in kidneys of mice with lethal endotoxemia and is transcriptionally upregulated in tubular cells by lipopolysaccharide (LPS) stimuli through TLR4/NF-κB cascade. The Adh1 knockout (Adh1KO) mice with lethal endotoxemia displayed increased susceptibility to acute kidney injury (AKI) but not systemic inflammatory response. Adh1KO mice develop more severe tubular cell apoptosis in comparison to Adh1 wild-type (Adh1WT) mice during course of lethal endotoxemia. ADH1 deficiency facilitates the LPS-induced tubular cell apoptosis in a caspase-dependent manner. Mechanistically, ADH1 deficiency dampens tubular mitophagy that relies on PINK1-Parkin pathway characterized by the reduced membrane potential, reactive oxygen species (ROS) and release of fragmented mtDNA to cytosol. Kidney-specific overexpression of PINK1 and Parkin by adeno-associated viral vector 9 (AAV9) delivery ameliorates AKI exacerbation in Adh1KO mice with lethal endotoxemia. Our study supports the notion that ADH1 is critical for blockade of tubular apoptosis mediated by mitophagy, allowing the rapid identification and targeting of alcohol-metabolic route applicable to septic AKI.

Eight-month intensive meditation-based intervention improves refractory hallucinations and delusions and quality of life in male inpatients with schizophrenia: a randomized controlled trial.

AIM: This study investigated the impact of an 8-month daily-guided intensive meditation-based intervention (iMI) on persistent hallucinations/delusions and health-related quality of life (QoL) in male inpatients with schizophrenia with treatment-refractory hallucinations and delusions (TRHDs). METHODS: A randomized controlled trial assigned 64 male inpatients with schizophrenia and TRHD equally to an 8-month iMI plus general rehabilitation program (GRP) or GRP alone. Assessments were conducted at baseline and the third and eighth months using the Positive and Negative Syndrome Scale (PANSS), 36-Item Short Form-36 (SF-36), and Five Facet Mindfulness Questionnaire (FFMQ). Primary outcomes measured PANSS reduction rates for total score, positive symptoms, and hallucinations/delusions items. Secondary outcomes assessed PANSS, SF-36, and FFMQ scores for psychotic symptoms, health-related QoL, and mindfulness skills, respectively. RESULTS: In the primary outcome, iMI significantly improved the reduction rates of PANSS total score, positive symptoms, and hallucination/delusion items compared with GRP at both the third and eighth months. Treatment response rates (≥25% reduction) for these measures significantly increased in the iMI group at the eighth month. Concerning secondary outcomes, iMI significantly reduced PANSS total score and hallucination/delusion items, while increasing scores in physical activity and mindfulness skills at both the third and eighth months compared with GRP. These effects were more pronounced with an 8-month intervention compared with a 3-month intervention. CONCLUSIONS: An iMI benefits patients with TRHDs by reducing persistent hallucinations/delusions and enhancing health-related QoL. Longer iMI duration yields superior treatment outcomes.

Polyploidization-enhanced effective clonal reproduction endows the successful invasion of Solidago canadensis.

Clonality and ploidy levels are positively associated with plant invasiveness. However, there is still no consensus on whether polyploidization can promote the invasion of alien plants by enhancing clonality. Our recent long-term community succession study found that the more vigorous clone of introduced polyploid Solidago canadensis succeeded into mono-dominant community, which seems to be a positive correlationship between polyploidization and clonal reproduction. However, the formation process of clonal ramet and how polyploidization improves the clonal reproduction of S. canadensis remains unknown. Here, we compared clonal growth ability among diploids and polyploids of S. canadensis from native and introduced ranges in a common garden. Results showed that the rhizomes of S. canadensis originated from axillary buds of dense nodes at the basal stem of seedling and then produced into clonal ramets from the rhizomes. Diploids had denser nodes and more buds, developed more rhizomes per unit mass and produced more clonal propagules at the early growth stage compared with polyploids. However, the number of juvenile and secondary rhizomes, as well as the diameter and length of rhizomes in polyploid populations was significantly higher or greater than those of diploids, and those clonal traits in introduced polyploids were significantly higher than in native polyploids. Moreover, a phalanx growth form was observed in native and introduced diploid populations, which allocated about 3% and 5% of the total biomass to rhizomes, respectively, resulting in short and weak rhizomes. However, native and introduced polyploids allocated about 35% and 40%, respectively, of the total biomass to rhizomes, resulting in long and strong rhizomes, which were guerrilla growth forms. This study firstly shows that polyploidization enhanced the effective clonal reproduction of S. canadensis through pre-adaptation and rapid post-adaptation evolution, and consequently contributed to its successful invasion.

Phage therapy for refractory periapical periodontitis caused by Enterococcus faecalis in vitro and in vivo.

A phage PEf771 that specifically infects and lyses pathogenic Enterococcus faecalis YN771 in patients with refractory periapical periodontitis was used to investigate resistance against E. faecalis infection in vitro and in vivo. PEf771 completely lysed YN771 within 3 h, with a multiplicity of infection of 1. Compared with ten routinely used clinical antibiotics, PEf771 demonstrated the highest bacteriostatic effect within 72 h. The antibacterial effect of PEf771 on extracted teeth within 72 h was better than that of conventional root canal disinfectants such as camphorated phenol, formaldehyde cresol solution, and Ca(OH)2 (P < 0.05) within 72 h. Using E. faecalis, intraperitoneal and periapical infection models were established using Sprague Dawley (SD) rats. The results showed that all SD rats inoculated with 9.6 × 1011 CFU/mL E. faecalis YN771 or 2.9 × 1011 CFU/mL E. faecalis RYN771 died within 8 h. Additionally, all SD rats inoculated with YN771 and treated with antibiotics died within 72 h. Although SD rats inoculated with RYN771 and treated with antibiotics survived for 72 h, the pathological anatomy of these rats showed purulent discharge, numerous pus and blood-filled ascites, and extensive liver abscesses. Notably, YN771 rats treated with PEf771 and RYN771 rats treated with RPEf771 survived for 72 h, and their pathological anatomy showed that the liver, kidneys, intestine, and mesenteries were normal. Computed tomography analysis of SD rats infected with periapical periodontitis showed pathological changes in experimental teeth inoculated with YN771, despite undergoing a normal root canal treatment. Contrastingly, none of the experimental teeth exhibited root periapical inflammation following PEf771 treatment. Hematoxylin and eosin staining revealed a gap between the periodontal ligament and the cementum of experimental teeth, whereas PEf771-treated teeth exhibited normal results. These findings suggested that phage therapy using PEf771 might effectively prevent E. faecalis infection after root canal treatment.Key points• Compared with common clinical antibiotics, PEf771 showed the highest antibacterial.• The liver, kidney, intestine, and mesentery of SD rats treated with PEf771 were normal.• Phage therapy can effectively prevent E. faecalis YN771 and RYN771 infection.

Acute fibrinous and organizing pneumonia in a patient with Sjögren's syndrome and Legionella pneumonia: a case report and literature review.

BACKGROUND: Acute fibrinous and organizing pneumonia (AFOP) is a rare clinicopathological condition. Studies in the literature have reported that AFOP may be associated with respiratory infections, such as respiratory syncytial virus, influenza virus, Pneumocystis jirovecii, Penicillium citrinum, and Chlamydia infections. However, AFOP associated with Legionella infection has not been reported previously. Here, we report a case of a patient with AFOP secondary to Sjögren's syndrome and Legionella infection. CASE PRESENTATION: A 47-year-old man was admitted to the hospital because of fever, expectoration, and shortness of breath. Lung imaging showed irregular patchy consolidation. A diagnosis of Legionella pneumonia was initially considered on the basis of the patient's history of exposure to soil before disease onset, signs of extrapulmonary involvement, and a positive Legionella urine antigen test result. However, the patient's symptoms and lung imaging did not improve after treatment with levofloxacin, moxifloxacin, and tigecycline for Legionella infection. In addition, Sjögren's syndrome was diagnosed on the basis of clinical manifestations and immunological indicators. Pathological changes associated with AFOP were confirmed from the results of ultrasound-guided percutaneous lung biopsy. The patient's clinical symptoms improved rapidly after a short course of low-dose corticosteroid therapy, and lung imaging showed significant improvement. CONCLUSIONS: The possibility of secondary AFOP should be considered when Legionella pneumonia does not improve after standard antibiotic therapy. Lung biopsy and histopathological examination are important for the adjustment of treatment strategy. Our case also highlights the importance of screening for autoimmune diseases in patients with AFOP.

Ascorbate uptake enables tubular mitophagy to prevent septic AKI by PINK1-PARK2 axis.

Ascorbate (Vitamin C) has been proposed as a promising therapeutic agent against sepsis in clinical trials, but there is little experimental evidence on its anti-septic efficacy. We report that Toll-like receptor 4 (TLR4) activation by LPS stimuli augments ascorbate uptake in murine and human tubular cells through upregulation of two ascorbate transporters SVCT-1 and -2 mediated by Fn14/SCFFbxw7α cascade. Ascorbate restriction, or knockout of SVCT-1 and -2, the circumstance reminiscent to blockade of ascorbate uptake, endows tubular cells more vulnerable to the LPS-inducible apoptosis, whereas exogenous administration of ascorbate overrides the ruin execution, for which the PINK1-PARK2, rather than BNIP3-NIX axis is required. Ascorbate increases, while SVCT-1 and -2 knockout or ascorbate restriction dampens tubular mitophagy upon LPS stimuli. Treatment of endotoxemic mice with high-dose ascorbate confers mitophagy and substantial protection against mortality and septic acute kidney injury (AKI). Our work provides a rationale for clinical management of septic AKI with high doses of ascorbate.

Genetic alterations and functional networks of m6A RNA methylation regulators in pancreatic cancer based on data mining.

BACKGROUND: Pancreatic cancer is a fatal malignancy of the digestive system and the 5-year survival rate remains low. Therefore, new molecular therapeutic targets are required to improve treatments, prognosis, and the survival of patients. N6-methyladenosine (m6A) is the most prevalent reversible methylation in mammalian messenger RNA (mRNA) and has critical roles in the tumorigenesis and metastasis of various malignancies. However, the role of m6A in pancreatic cancer is still unclear. Exploring genetic alterations and functional networks of m6A regulators in pancreatic cancer may provide new strategies for its treatment. METHODS: In this study, we used data from the Cancer Genome Atlas (TCGA) database and other public databases through cBioPortal, LinkedOmics, UALCAN, GEPIA, STRING, and the database for annotation, visualization, and integrated discovery (DAVID) to systematically analyze the molecular alterations and functions of 20 main m6A regulators in pancreatic cancer. RESULTS: We found that m6A regulators had widespread genetic alterations, and that their expression levels were significantly correlated with pancreatic cancer malignancy. Moreover, m6A regulators were associated with the prognosis of pancreatic cancer patients. CONCLUSIONS: m6A regulators play a crucial part in the occurrence and development of pancreatic cancer. Our study will guide further studies of m6A RNA modification in pancreatic cancer and could potentially provide new strategies for pancreatic cancer treatment.

Association between fasting blood glucose levels at admission and overall survival of patients with pancreatic cancer.

BACKGROUND: The associations between fasting blood glucose and staging and overall survival of patients with pancreatic cancer are still controversial. This study aimed to investigate the association between fasting blood glucose levels and overall survival (OS) of patients with pancreatic cancer and to evaluate the impact of differentiation and staging of pancreatic cancer. METHODS: This was a retrospective study of patients with pathologically confirmed pancreatic cancer admitted to Shengjing Hospital of China Medical University between 01/2012 and 12/2016. The outcome was the OS. The factors associated with OS were examined using univariable and multivariable Cox and logistic regression analyses. RESULTS: A total of 253 patients were included. Preoperative blood glucose levels were not significantly associated with the OS of patients with pancreatic cancer (HR = 1.04, 95%CI: 0.78-1.40, P = 0.781). Only CA199 > 1000 was independently associated with OS (HR = 1.86, 95%CI: 1.15-3.02, P = 0.012). The median survival in the normal glucose group was 20.5 months (95% confidence interval (CI): 14.2-26.9). The median survival in the high glucose group was 14.2 months (95% CI: 9.7-18.6). There was no statistically significant difference between the two groups (P = 0.573). Multivariable logistic regression analyses were performed to determine if blood glucose levels influenced the 1- and 2-year OS. No significant association was observed for 1-year (OR = 1.27, 95%CI: 0.71-2.29, P = 0.418) or 2-year (HR = 1.37, 95%CI: 0.76-2.46, P = 0.296) OS. CONCLUSIONS: Fasting blood glucose levels are not associated with the OS of patients with pancreatic adenocarcinoma.

Domino effect of pituitary growth hormone tumor complicated by diabetic ketoacidosis and pituitary apoplexy: a case report.

BACKGROUND: Patients with growth hormone (GH)-secreting adenoma usually develop glucose intolerance. GH increases metabolic rate and, when secreted aberrantly, may result in metabolic syndrome. Herein, we examine the associations of pituitary tumor-induced secretion of hormone with insulin resistance and metabolic syndrome, and determine the relation of pituitary tumor apoplexy-induced diabetic ketoacidosis (DKA) and acute pancreatitis. CASE PRESENTATION: A 44-year-old male with a history of hypertension presented to the emergency department of our hospital on February 14, 2019 with symptoms of headache, dizziness, and vomiting. Computed tomography of the head revealed pituitary tumor with bleeding. An ultrasound scan of the abdomen revealed fatty liver and acute pancreatitis. Further examination revealed the presence of DKA, hypertriglyceridemia, cortical hypofunction crisis and acute kidney injury. Surgical endoscopic resection of the pituitary tumor resection via the transsphenoidal approach was performed. The patient's postoperative recovery was remarkable. CONCLUSIONS: Long-term growth hormone abnormality may trigger insulin resistance, leading to metabolic syndrome and impaired glucose and lipid metabolism. The pituitary adenoma apoplexy may also directly induce DKA, creating a domino effect, which further deteriorate the aberrant metabolism of glucose and lipids.

lncRNA-SNHG14 Plays a Role in Acute Lung Injury Induced by Lipopolysaccharide through Regulating Autophagy via miR-223-3p/Foxo3a.

lncRNAs play important roles in lipopolysaccharide- (LPS-) induced acute lung injury. But the mechanism still needs further research. In the present study, we investigate the functional role of the lncRNA-SNHG14/miR-223-3p/Foxo3a pathway in LPS-induced ALI and tried to confirm its regulatory effect on autophagy. Transcriptomic profile changes were identified by RNA-seq in LPS-treated alveolar type II epithelial cells. The expression changes of lncRNA-SNHG14/miR-223-3p/Foxo3a were confirmed using qRT-PCR and west blot. The binding relationship of lncRNA-SNHG14/miR-223-3p/and miR-223-3p/Foxo3a was verified using dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays. Using gain-of-function or loss-of-function approaches, the effect of lncRNA-SNHG14/miR-223-3p/Foxo3a was investigated in LPS-induced acute lung injury mice model and in vitro. Increasing of lncRNA-SNHG14 and Foxo3a with reducing miR-223-3p was found in LPS-treated A549 cells and lung tissue collected from the LPS-induced ALI model. lncRNA-SNHG14 inhibited miR-223-3p but promoted Foxo3a expression as a ceRNA. Artificially changes of lncRNA-SNHG14/miR-223-3p/Foxo3a pathway promoted or protected cell injury from LPS in vivo and in vitro. Autophagy activity could be influenced by lncRNA-SNHG14/miR-223-3p/Foxo3a pathway in cells with or without LPS treatment. In conclusion, aberrant expression changes of lncRNA-SNHG14 participated alveolar type II epithelial cell injury and acute lung injury induced by LPS through regulating autophagy. One underlying mechanism is that lncRNA-SNHG14 regulated autophagy by controlling miR-223-3p/Foxo3a as a ceRNA. It suggested that lncRNA-SNHG14 may serve as a potential therapeutic target for patients with sepsis-induced ALI.

Knockdown of G-protein-signaling modulator 2 promotes metastasis of non-small-cell lung cancer by inducing the expression of Snail.

Non-small-cell lung cancer (NSCLC) is the leading global cause of cancer-related death. Due to the lack of reliable diagnostic or prognostic biomarkers, the prognosis of NSCLC remains poor. Consequently, there is an urgent need to explore the mechanisms underlying this condition in order to identify effective biomarkers. G-protein-signaling modulator 2 (GPSM2) is widely recognized as a determinant of mitotic spindle orientation. However, its role in cancer, especially NSCLC, remains uncertain. In this study, we found that GPSM2 was downregulated in NSCLC tissues and was correlated with a poor prognosis. Furthermore, the knockdown of GPSM2 promoted NSCLC cell metastasis in vitro and in vivo and accelerated the process of epithelial-mesenchymal transition (EMT). Mechanistically, we showed that silencing GPSM2 induced cell metastasis and EMT through the ERK/glycogen synthase kinase-3ß/Snail pathway. These results confirm that GPSM2 plays an important role in NSCLC. Moreover, GPSM2, as an independent prognostic factor, could be a potential prognostic biomarker and drug target for NSCLC.

Polyploidization-driven differentiation of freezing tolerance in Solidago canadensis.

Solidago canadensis, originating from the temperate region of North America, has expanded southward to subtropical regions through polyploidization. Here we investigated whether freezing tolerance of S. canadensis was weakened during expansion. Measurement of the temperature causing 50% ruptured cells (LT50 ) in 35 S. canadensis populations revealed ploidy-related differentiation in freezing tolerance. Freezing tolerance was found to decrease with increasing ploidy. The polyploid populations of S. canadensis had lower ScICE1 gene expression levels but more ScICE1 gene copies than the diploids. Furthermore, more DNA methylation sites in the ScICE1 gene promoter were detected in the polyploids than in the diploids. The results suggest that promoter methylation represses the expression of multi-copy ScICE1 genes, leading to weaker freezing tolerance in polyploid S. canadensis compared to the diploids. The study provides empirical evidence that DNA methylation regulates expression of the gene copies and supports polyploidization-driven adaptation to new environments.

Prevalence and impact of acute renal impairment on COVID-19: a systematic review and meta-analysis.

BACKGROUND: The aim of this study is to assess the prevalence of abnormal urine analysis and kidney dysfunction in COVID-19 patients and to determine the association of acute kidney injury (AKI) with the severity and prognosis of COVID-19 patients. METHODS: The electronic database of Embase and PubMed were searched for relevant studies. A meta-analysis of eligible studies that reported the prevalence of abnormal urine analysis and kidney dysfunction in COVID-19 was performed. The incidences of AKI were compared between severe versus non-severe patients and survivors versus non-survivors. RESULTS: A total of 24 studies involving 4963 confirmed COVID-19 patients were included. The proportions of patients with elevation of sCr and BUN levels were 9.6% (95% CI 5.7-13.5%) and 13.7% (95% CI 5.5-21.9%), respectively. Of all patients, 57.2% (95% CI 40.6-73.8%) had proteinuria, 38.8% (95% CI 26.3-51.3%) had proteinuria +, and 10.6% (95% CI 7.9-13.3%) had proteinuria ++ or +++. The overall incidence of AKI in all COVID-19 patients was 4.5% (95% CI 3.0-6.0%), while the incidence of AKI was 1.3% (95% CI 0.2-2.4%), 2.8% (95% CI 1.4-4.2%), and 36.4% (95% CI 14.6-58.3%) in mild or moderate cases, severe cases, and critical cases, respectively. Meanwhile, the incidence of AKI was 52.9%(95% CI 34.5-71.4%), 0.7% (95% CI - 0.3-1.8%) in non-survivors and survivors, respectively. Continuous renal replacement therapy (CRRT) was required in 5.6% (95% CI 2.6-8.6%) severe patients, 0.1% (95% CI - 0.1-0.2%) non-severe patients and 15.6% (95% CI 10.8-20.5%) non-survivors and 0.4% (95% CI - 0.2-1.0%) survivors, respectively. CONCLUSION: The incidence of abnormal urine analysis and kidney dysfunction in COVID-19 was high and AKI is closely associated with the severity and prognosis of COVID-19 patients. Therefore, it is important to increase awareness of kidney dysfunction in COVID-19 patients.

A Comparison of Clinical Characteristics and Outcomes in Elderly and Younger Patients with COVID-19.

BACKGROUND The aim of this study was to describe the clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) and compare these parameters in an elderly group with those in a younger group. MATERIAL AND METHODS This retrospective, single-center observational study included 69 hospitalized patients with laboratory-confirmed COVID-19 from a tertiary hospital in Wuhan, China, between January 14, 2020, and February 26, 2020. Epidemiological, demographic, clinical, and laboratory data, as well as treatments, complications, and outcomes were extracted from electronic medical records and compared between elderly patients (aged ≥60 years) and younger patients (aged <60 years). Patients were followed until March 19, 2020. RESULTS Elderly patients had more complications than younger patients, including acute respiratory distress syndrome (ARDS; 9/25, 36% vs. 5/44, 11.4%) and cardiac injury (7/25, 28% vs. 1/44, 2.3%), and they were more likely to be admitted to the intensive care unit (6/25, 24% vs. 2/44, 4.5%). As of March 19, 2020, 60/69 (87%) of the patients had been discharged, 6/69 (8.7%) had died, and 3/69 (4.3%) remained in the hospital. Of those who were discharged or died, the median duration of hospitalization was 13.5 days (interquartile range, 10-18 days). CONCLUSIONS Elderly patients with confirmed COVID-19 were more likely to develop ARDS and cardiac injury than younger patients and were more likely to be admitted to the intensive care unit. In addition to routine monitoring and respiratory support, cardiac monitoring and supportive care should be a focus in elderly patients with COVID-19.

Biological characteristics and whole-genome analysis of the Enterococcus faecalis phage PEf771.

Enterococcus faecalis is a common pathogen causing refractory periapical periodontitis and secondary intraradicular infections. In this study, E. faecalis YN771 isolated from a re-treated root canal at a stomatology department was used as the host bacterium and was co-cultured with wastewater from the same department and patient samples to isolate a phage that lyses E. faecalis. We studied the biological and genomic characteristics of this phage. Transmission electron microscopy showed that this phage's head is icosahedral in structure, with a head diameter of around 98.4 nm, and a contractile tail of around 228.5 nm in length and a diameter of 17.3 nm. The phage was identified as a member of the Myoviridae family and named PEf771. It is sensitive to proteinase K but resistant to chloroform and Triton X-100. Its lytic cycle is 45 min, burst size is 78, optimal multiplicity of infection is 0.1, lysis spectrum is narrow, and host strain specificity is strong. Its optimal growth temperature is 37 °C, most suitable pH is 6.0, and is sensitive to ultraviolet radiation. Whole-genome sequencing of PEf771 indicated it has a genome size of 151 052 bp, with a GC content of 36.97%, and encodes 197 proteins plus 26 tRNAs. PEf771 is most closely related to E. faecalis phage EFDG1. Phage PEf771 has strong host specificity and lytic ability, so it is important to further characterize this phage and its interaction with E. faecalis.

Effect of mandibular advancement device on the stomatognathic system in patients with mild-to-moderate obstructive sleep apnoea-hypopnoea syndrome.

OBJECTIVE: This study was conducted to evaluate the changes of temporomandibular joints (TMJs) through magnetic resonance imaging (MRI) scanning and the electrical changes in mandibular movement and masticatory muscle surface of mild-to-moderate obstructive sleep apnoea-hypopnoea syndrome (OSAHS) patients before and after treatment with mandibular advancement device (MAD). METHODS: This was a single-centre, prospective study recruiting OSAHS patients undergoing treatment with MAD in Department of Stomatology, Yannan Hospital, Kunming, China. Patients were recruited from February 2015 to October 2015, and TMJ changes were observed in MRI scanning before and after 18 months of treatment with MAD in cohort 1. The second cohort of the patients were recruited from January 2014 to September 2015 and electrical changes in mandibular movement and masticatory muscle surface of patients before and after 6 months of treatment with MAD. RESULTS: In the cohort 1, TMJ changes analysed through MRI scanning, before and after 18-month treatment with MAD, there was no significant deviation in the angle of joint disc position. A minor change in the position relationship between condylar process, articular disc and articular fossa but not significant was observed. There was no significant difference in the shape and magnitude of mandibular incision edge movement, percussion movement, masticatory movement and condylar central trajectory among the recruited OSAHS patients, before and after 6 months of MAD treatment as analysed through electromyography. CONCLUSION: In this study, from the results it was evident that the effect of MAD on the stomatognathic system of OSAHS patients is minimal.

Long noncoding RNA LINC00473 drives the progression of pancreatic cancer via upregulating programmed death-ligand 1 by sponging microRNA-195-5p.

Pancreatic cancer (PC) is a great health burden to patients owing to its poor overall survival rate. Long noncoding RNAs (lncRNAs) interact with microRNAs (miRs) to participate in tumorigenesis. Therefore, we aim to uncover the role and related mechanism of LINC00473 in PC through the modulation of miR-195-5p and programmed death-ligand 1 (PD-L1). Increased LINC00473 and PD-L1 but declined miR-195-5p were determined in PC tissues and cell lines, and it was found that LINC00473 mainly situated in the cytoplasm. Also, miR-195-5p was verified to bind with both LINC00473 and PD-L1. Next, with the aim to examine the ability of LINC00473, miR-195-5p, and PD-L1 on the PC progression, the expression of LINC00473, miR-195-5p and PD-L1 were altered with mimics, inhibitors, overexpression vectors or siRNAs in PC cells and cocultured CD8+ T cells. It was demonstrated that LINC00473 sponged miR-195-5p to upregulate PD-L1 expression. More important, the obtained results revealed that LINC00473 silencing or miR-195-5p upregulation elevated the expression of Bcl-2 associated X protein (Bax), interferon (IFN)-γ, and interleukin (IL)-4 but reduced the expression of B-cell lymphoma-2 (Bcl-2), matrix metalloproteinase (MMP)-2, MMP-9, and IL-10, thus inducing the enhancement of the apoptosis as along with the inhibition of proliferation, invasion, and migration of the PC cells. LINC00473 silencing or miR-195-5p elevation activated the CD8+ T cells. Taken together, LINC00473 silencing blocked the PC progression through enhancing miR-195-5p-targeted downregulation of PD-L1. This finding offers new therapeutic options for treating this devastating disease.

Regulation of Fn14 stability by SCFFbxw7α during septic acute kidney injury.

Acute kidney injury (AKI) initiated by sepsis remains a thorny problem despite recent advancements in its clinical management. Having been found to be activated during AKI, fibroblast growth factor-inducible molecule 14 (Fn14) may be a potential therapeutic target because of its involvement in the molecular basis of injury. Here, we report that LPS induces apoptosis of mouse cortical tubule cells mediated by Fn14, for which simultaneous Toll-like receptor (TLR)4 activation is required. Mechanistically, TLR4 activation by lipopolysaccharide, through disassociating E3 ligase SCFFbxw7α from Fn14, dismantles Lys48-linked polyubiquitination of Fn14 and stabilizes it. Pharmacological deactivation of Fn14 with monoclonal antibody ITEM-2 provides effective protection against lethal sepsis and AKI in mice. Our study underscores an adaptive mechanism whereby TLR4 regulates SCFFbxw7α-dependent Fn14 stabilization during inflammatory tubular damage and further supports investigation of targeting Fn14 in clinical trials of patients with septic AKI.

Isolated metastasis of hepatocellular carcinoma in the right ventricle.

BACKGROUND: Hepatocellular carcinoma (HCC) with right ventricle metastasis without inferior vena cava and right atrium involvement is very rare and the prognosis of HCC with RV metastasis is generally poor. The mass in the cardiac chamber may lead to lethal instability of hemodynamics, however, the initial symptom is probably non-specific, which means that diagnosis timely becomes even harder. CASE PRESENTATION: We present a 63-year-old male with isolated metastasis of HCC in the right ventricle which caused inflow obstruction. Moreover, we reviewed a series of studies of isolated metastasis of hepatocellular carcinoma between 1980 and 2018, and summarized the relative outcomes. CONCLUSIONS: Isolated metastasis of hepatocellular carcinoma in the right ventricle is extraordinarily rare. It may damage cardiac structure and broke hemodynamic balance. Multimodality imaging plays an important in accurate pre-operation assessment. Nowadays, palliative treatments could relieve fatal symptoms to some degree, however, standard treatment has not been well established.