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.

Design, synthesis, and biological evaluation of 2-amino-6-methyl-phenol derivatives targeting lipid peroxidation with potent anti-ferroptotic activities.

The suppression of ferroptosis is emerging as a promising therapeutic strategy for effectively treating a wide range of diseases, including neurodegenerative disorders, organ ischemia-reperfusion injury, and inflammatory conditions. However, the clinical utility of ferroptosis inhibitors is significantly impeded by the limited availability of rational drug designs. In our previous study, we successfully unraveled the efficacy of ferrostatin-1 (Fer-1) attributed to the synergistic effect of its ortho-diamine (-NH) moiety. In this study, we present the discovery of the ortho-hydroxyl-amino moiety as a novel scaffold for ferroptosis inhibitors, employing quantum chemistry as well as in vitro and in vivo assays. 2-amino-6-methylphenol derivatives demonstrated remarkable inhibition of RSL3-induced ferroptosis, exhibiting EC50 values ranging from 25 nM to 207 nM. These compounds do not appear to modulate iron homeostasis or lipid reactive oxygen species (ROS) generation pathways. Nevertheless, they effectively prevent the accumulation of lipid peroxides in living cells. Furthermore, compound 13 exhibits good in vivo activities as it effectively protect mice from kidney ischemia-reperfusion injury. In summary, compound 13 has been identified as a potent ferroptosis inhibitor, warranting further investigation as a promising lead compound.

Etiology of lower respiratory tract in pneumonia based on metagenomic next-generation sequencing: a retrospective study.

Introduction: Pneumonia are the leading cause of death worldwide, and antibiotic treatment remains fundamental. However, conventional sputum smears or cultures are still inefficient for obtaining pathogenic microorganisms.Metagenomic next-generation sequencing (mNGS) has shown great value in nucleic acid detection, however, the NGS results for lower respiratory tract microorganisms are still poorly studied. Methods: This study dealt with investigating the efficacy of mNGS in detecting pathogens in the lower respiratory tract of patients with pulmonary infections. A total of 112 patients admitted at the First Affiliated Hospital of Zhengzhou University between April 30, 2018, and June 30, 2020, were enrolled in this retrospective study. The bronchoalveolar lavage fluid (BALF) was obtained from lower respiratory tract from each patient. Routine methods (bacterial smear and culture) and mNGS were employed for the identification of pathogenic microorganisms in BALF. Results: The average patient age was 53.0 years, with 94.6% (106/112) obtaining pathogenic microorganism results. The total mNGS detection rate of pathogenic microorganisms significantly surpassed conventional methods (93.7% vs. 32.1%, P < 0.05). Notably, 75% of patients (84/112) were found to have bacteria by mNGS, but only 28.6% (32/112) were found to have bacteria by conventional approaches. The most commonly detected bacteria included Acinetobacter baumannii (19.6%), Klebsiella pneumoniae (17.9%), Pseudomonas aeruginosa (14.3%), Staphylococcus faecium (12.5%), Enterococcus faecium (12.5%), and Haemophilus parainfluenzae (11.6%). In 29.5% (33/112) of patients, fungi were identified using mNGS, including 23 cases of Candida albicans (20.5%), 18 of Pneumocystis carinii (16.1%), and 10 of Aspergillus (8.9%). However, only 7.1 % (8/112) of individuals were found to have fungi when conventional procedures were used. The mNGS detection rate of viruses was significantly higher than the conventional method rate (43.8% vs. 0.9%, P < 0.05). The most commonly detected viruses included Epstein-Barr virus (15.2%), cytomegalovirus (13.4%), circovirus (8.9%), human coronavirus (4.5%), and rhinovirus (4.5%). Only 29.4% (33/112) of patients were positive, whereas 5.4% (6/112) of patients were negative for both detection methods as shown by Kappa analysis, indicating poor consistency between the two methods (P = 0.340; Kappa analysis). Conclusion: Significant benefits of mNGS have been shown in the detection of pathogenic microorganisms in patients with pulmonary infection. For those with suboptimal therapeutic responses, mNGS can provide an etiological basis, aiding in precise anti-infective treatment.

Immunosuppressive drugs to reduce the mortality rate in patients with moderate to severe paraquat poisoning: A Meta-analysis.

The benefits and adverse effects of immunosuppressive drugs (ISDs) in patients with paraquat (PQ) poisoning have not been thoroughly assessed. This meta-analysis study aims to evaluate the effect of ISDs in patients with moderate to severe PQ poisoning. We searched PubMed, Embase, Cochrane Library, Ovid Medline, CNKI and Wanfang Data from inception to January 2019. The Mantel-Haenszel method with a random-effects model was used to calculate the pooled relative risks (RRs) and 95% Confidence Intervals (CIs) as described by DerSimonian and Laird. An L'Abbé plot was drawn to explore the relationship between the degree of poisoning and mortality. Four randomized controlled trials, two prospective and seven retrospective studies were identified. ISDs were significantly associated with reduced mortality (RR 0.76; 95% CI, 0.58-0.99) and the incidence rate of multiple-organ dysfunction syndrome (MODS) (RR 0.63; 95% CI, 0.48-0.83) in patients with moderate to severe PQ poisoning. They were not associated with an increased incidence rate of hepatitis and reduced incidence rate of acute renal failure and hypoxia. The L'Abbé plot results showed a slight increase in mortality rate in the ISD group with increased mortality in the placebo group. This indicates a possible advantage of ISDs in most of the patients with severe PQ poisoning. These findings suggest that ISDs may reduce the mortality and incidence rate of MODS in moderate to severe PQ poisoning patients, and severe PQ poisoning patients might benefit more from ISDs.

Bone marrow mesenchymal stem cells modified by angiogenin-1 promotes tissue repair in mice with oxygen-induced retinopathy of prematurity by promoting retinal stem cell proliferation and differentiation.

Retinopathy has become one of the major factors that lead to blindness worldwide. Although many clinical therapies are concerned about such disease, most of them focus on symptoms alleviation. In this study, we aim to investigate whether coculture retinal stem cells (RSCs) with bone marrow mesenchymal stem cells transfected with angiogenin-1 (Ang-1-BMSCs) affects the damaged retinal tissue of oxygen-induced retinopathy of prematurity (OIR-ROP) mice. After OIR-ROP mouse model establishment, Ang-1-BMSCs, RSCs, and OIR-ROP retinal tissues were cocultured in a a transwell chamber. RSCs proliferation and the expression of Ang-1, insulin-like growth factor-1 (IGF-1) in the supernatant of RSCs, as well as ß-tubulin and protein kinase C (PKC) expression were evaluated. Finally, the repair of OIR-ROP mice retinal tissues was observed by injecting Ang-1-BMSCs + RSCs. In the OIR-ROP mouse model, RSCs cocultured with OIR-ROP retinal tissues could be induced to differentiate into cells expressing ß-tubulin and PKC and promote the expression of Ang-1 and IGF-1. coculture of Ang-1-BMSCs further enhanced the proliferation and differentiation of RSCs by promoting the expression of Ang-1 and IGF-1. Coculture of RSCs + Ang-1-BMSCs induced differentiation of Ang-1-BMSCs through interaction among intercellular factors and restored the damaged retinal tissue of OIR-ROP mice. Collectively, our study provided evidence that coculture of Ang-1-BMSCs and RSCs could promote the proliferation and differentiation of RSCs and improve the treatment for the damaged retina tissue of OIR-ROP mice.

Effects of bone marrow mesenchymal stem cells transfected with Ang-1 gene on hyperoxia-induced optic nerve injury in neonatal mice.

Optic nerve injury triggered retinal ganglion cell (RGC) death and optic nerve atrophy lead to visual loss. Bone marrow mesenchymal stem cells (BMSCs) are stromal cells, capable of proliferating and differentiating into different types of tissues. This aims of this study is to investigate the role of BMSCs transfected with angiopoietin-1 (Ang-1) in optic nerve injury induced by hyperoxia in a neonatal mice model. Ang-1 overexpression vector was constructed and used to transfect BMSCs. Reverse transcription-quantitative polymerase chain reaction was performed to detect Ang-1 expression in BMSCs. The hyperoxia-induced optic nerve injury model was established. The optic nerves at 6-7 mm posterior to the eyeball were extracted, and were treated with luxol fast blue staining, immunohistochemistry, immunofluorescence, and transmission electron microscopy to examine the effects of Ang-1-modified BMSCs on optic nerve injury induced by hyperoxia. The mice in the Ang-1 + BMSCs and BMSCs groups showed remarkably improved myelin sheaths of nerve fibers compared to the hyperoxia saline group. The positive expression and integrated optic density of Ang-1 in the Ang-1 + BMSCs group were significantly higher compared to the air control, hyperoxia saline and BMSCs groups. The number and diameter of myelinated nerve fibers, the diameter of axons and the thickness of myelin sheath in the air control and Ang-1 + BMSCs groups were higher compared to the hyperoxia saline group. Our study provides evidence supporting that Ang-1-modified BMSCs may have preventive and therapeutic effects on hyperoxia-induced optic nerve injury in neonatal mice.

[Effects of ulinastatin on myocardial injury induced by acute paraquat poisoning].

OBJECTIVE: To investigate the effects of ulinastatin (UTI) on myocardial injury induced by acute paraquat poisoning. METHODS: Twenty-four Japan white rabbits were divided into control group, model group (37 mg/kg paraquat intraperitoneally once), UTI low dosage group and high dosage group [25 kU×kg(-1)×d(-1) and 50 kU×kg(-1)×d(-1) UTI was intravenously injected respectively for 9 days beginning from 1 week before poisoning] through random number table. Rabbits were sacrificed 24 hours after the last UTI administration. Left ventricle of hearts were harvest, and tissue hydroxyproline (HYP) contents were determined. Matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) transcriptional levels were assayed respectively with reverse transcription-polymerase chain reaction (RT-PCR). Expression levels of MMP-2 in tissue of left ventricle were quantified with immunohistochemistry. RESULTS: Compared with normal myocardium, acute paraquat poisoning induced elevated HYP (mg/g) content significantly (3.85 ± 0.36 vs. 2.52 ± 0.29, P < 0.05); with RT-PCR and immunohistochemistry, it was shown that both mRNA expression levels and immunohistochemistry score of MMP-2 were much higher (mRNA: 2.07 ± 0.57 vs. 1.00 ± 0.35; immunohistochemistry score: 2.24 ± 0.82 vs. 1.40 ± 0.62, both P < 0.05). TIMP-2 appeared to be down-regulated in mRNA expression level (0.78 ± 0.24 vs. 1.00 ± 0.17, P > 0.05). Disorganized cardiocytes were observed. Compared with paraquat poisoning model, low and high UTI administration produced depression of tissue HYP contents (3.40 ± 0.48, 3.12 ± 0.43 vs. 3.85 ± 0.36, P > 0.05 and P < 0.05). With low or high dosage of UTI reduced mRNA expression levels and immunohistochemical scores of MMP-2 in left ventricle were observed (mRNA: 1.86 ± 0.44, 1.58 ± 0.46 vs. 2.07 ± 0.57, P > 0.05 and P < 0.05; immunohistochemical score: 1.93 ± 0.86, 1.75 ± 0.67 vs. 2.24 ± 0.82, both P < 0.05), and TIMP-2 mRNA level was increased slightly, though there was no significant differences (0.82 ± 0.35, 0.94 ± 0.33 vs. 0.78 ± 0.24, both P > 0.05). Improvements in disordered myocardium were demonstrated. CONCLUSIONS: UTI significantly attenuated myocardial injury induced by acute paraquat poisoning. Its mechanism might be related to a reduction of expression level of MMP-2 in tissue, with a dose-dependent manner.

[Expression of cyclooxygenase-2 in bladder transitional cell carcinoma and the significance thereof].

OBJECTIVE: To study the expression of cyclooxygenase-2 (COX-2) in bladder transitional cell carcinoma (Tcc) and the clinical significance thereof. METHODS: Immunohistochemistry was used to detect the expression of COX-2 in 56 specimens of bladder Tcc and 10 specimens of normal bladder tissue, all resected during operation. RESULTS: No expression of COX-2 was detected in the 10 specimens of normal bladder tissue and in the 56 specimens of bladder Tcc the positive rate of COX-2 was 55.36%. The expression of COX-2 in bladder Tcc was closely correlated with the grade and stage of tumor (both P < 0.01). CONCLUSION: COX-2 expression in bladder Tcc is closely correlated with the grade and stage.