Effective treatment of severe COVID-19 patients with tocilizumab.

After analyzing the immune characteristics of patients with severe coronavirus disease 2019 (COVID-19), we have identified that pathogenic T cells and inflammatory monocytes with large amount of interleukin 6 secreting may incite the inflammatory storm, which may potentially be curbed through monoclonal antibody that targets the IL-6 pathways. Here, we aimed to assess the efficacy of tocilizumab in severe patients with COVID-19 and seek a therapeutic strategy. The patients diagnosed as severe or critical COVID-19 in The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) and Anhui Fuyang Second People's Hospital were given tocilizumab in addition to routine therapy between 5 and 14 February 2020. The changes of clinical manifestations, computerized tomography (CT) scan image, and laboratory examinations were retrospectively analyzed. Fever returned to normal on the first day, and other symptoms improved remarkably within a few days. Within 5 d after tocilizumab, 15 of the 20 patients (75.0%) had lowered their oxygen intake, and 1 patient needed no oxygen therapy. CT scans manifested that the lung lesion opacity absorbed in 19 patients (90.5%). The percentage of lymphocytes in peripheral blood, which decreased in 85.0% of patients (17/20) before treatment (mean, 15.52 ± 8.89%), returned to normal in 52.6% of patients (10/19) on the fifth day after treatment. Abnormally elevated C-reactive protein decreased significantly in 84.2% of patients (16/19). No obvious adverse reactions were observed. All patients have been discharged on average 15.1 d after giving tocilizumab. Preliminary data show that tocilizumab, which improved the clinical outcome immediately in severe and critical COVID-19 patients, is an effective treatment to reduce mortality.

P/N-Heteroleptic Cu(I)-Photosensitizer-Catalyzed [3 + 2] Regiospecific Annulation of Aminocyclopropanes and Functionalized Alkynes.

We report here a regiospecific [3 + 2] annulation between aminocyclopropanes and various functionalized alkynes enabled by a P/N-heteroleptic Cu(I) photosensitizer under photoredox catalysis conditions. Thus, a divergent construction of 3-aminocyclopentene derivatives including methylsulfonyl-, arylsulfonyl-, chloro-, ester-, and trifluoromethyl-functionalized aminocyclopentenes could be achieved with advantages of high regioselectivity, broad substrate compatibility, and mild and environmentally benign reaction conditions.

The value of high-flow nasal cannula oxygen therapy in treating novel coronavirus pneumonia.

OBJECTIVE: This study aimed to investigate the value of high-flow nasal cannula (HNFC) oxygen therapy in treating patients with severe novel coronavirus pneumonia (COVID-19). METHODS: The clinical data of 22 patients with severe COVID-19 were collected. The heart rate (HR), respiratory rate (RR) and oxygenation index (PO2 /FiO2 ) at 0, 6, 24 and 72 hours after treatment were compared between the HFNC oxygen therapy group and the conventional oxygen therapy (COT) group. In addition, the white blood cell (WBC) count, lymphocyte (L) count, C-reactive protein (CRP) and procalcitonin (PCT) were compared before and at 72 hours after oxygen therapy treatment. RESULTS: The differences at 0 hours between the two groups were not statistically significant. Compared with COT group,in the HFNC oxygen therapy group, HR, RR and PaO2 /FiO2 were better at 6 hours after treatment, PaO2 /FiO2 was better at 24 and 72 hours. After 72 hours, L and CRP had improved in the HFNC oxygen therapy group compared with the COT group, but the differences in WBC and PCT were not statistically significant. The length of stay in the intensive care unit (ICU) and the total length of hospitalization was shorter in the HFNC oxygen therapy group than in the COT group. CONCLUSION: Compared with COT, early application of HFNC oxygen therapy in patients with severe COVID-19 can improve oxygenation and RR, and HFNC oxygen therapy can improve the infection indexes of patients and reduce the length of stay in the ICU of patients. Therefore, it has high clinical application value.

Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19.

The role of clinical laboratory data in the differential diagnosis of the severe forms of COVID-19 has not been definitely established. The aim of this study was to look for the warning index in severe COVID-19 patients. We investigated 43 adult patients with COVID-19. The patients were classified into mild group (28 patients) and severe group (15 patients). A comparison of the hematological parameters between the mild and severe groups showed significant differences in interleukin-6 (IL-6), d-dimer (d-D), glucose, thrombin time, fibrinogen, and C-reactive protein (P < .05). The optimal threshold and area under the receiver operator characteristic curve (ROC) of IL-6 were 24.3 and 0.795 µg/L, respectively, while those of d-D were 0.28 and 0.750 µg/L, respectively. The area under the ROC curve of IL-6 combined with d-D was 0.840. The specificity of predicting the severity of COVID-19 during IL-6 and d-D tandem testing was up to 93.3%, while the sensitivity of IL-6 and d-D by parallel test in the severe COVID-19 was 96.4%. IL-6 and d-D were closely related to the occurrence of severe COVID-19 in the adult patients, and their combined detection had the highest specificity and sensitivity for early prediction of the severity of COVID-19 patients, which has important clinical value.

Assessing SARS-CoV-2 RNA levels and lymphocyte/T cell counts in COVID-19 patients revealed initial immune status as a major determinant of disease severity.

The magnitude of SARS-CoV-2 infection, the dynamic changes of immune parameters in patients with the novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear. The clinical and laboratory results from 154 confirmed COVID-19 patients were collected. The SARS-CoV-2 RNA levels in patients were estimated using the Ct values of specific RT-PCR tests. The lymphocyte subsets and cytokine profiles in the peripheral blood were analyzed by flow cytometry and specific immunoassays. 154 confirmed COVID-19 patients were clinically examined up to 4 weeks after admission. The initial SARS-CoV-2 RNA Ct values at admission varied, but were comparable in the patient groups classified according to the age, gender, underlying diseases, and disease severity. Three days after admission, significant higher Ct values were found in severe cases. Significantly reduced counts of T cells and T cell subsets were found in patients with old age and underlying diseases at admission and were characteristic for the development of severe COVID-19. Severe COVID-19 developed preferentially in patients with underlying compromised immunity and was not associated with initial virus levels. Higher SARS-CoV-2 RNA levels in severe cases were apparently a result of impaired immune control associated with dysregulation of inflammation.

A Study on the Predictors of Disease Severity of COVID-19.

BACKGROUND Early and rapid identification of severe coronavirus disease 2019 (COVID-19) cases is important. The present study aimed to investigate the predictors of disease severity and thus determine the trends for disease progression early. MATERIAL AND METHODS Patients with COVID-19 were recruited from Fuyang Second People's Hospital from January to February 2020. Patients' demographic, epidemiological, and clinical data were collected, and the relationships between these variables and disease severity were analyzed. RESULTS A total of 158 cases were included according to COVID-19 diagnosis, and the treatment schemes were analyzed for identification of early indicators affecting COVID-19 progression. Severe cases accounted for 18.99% of the diagnosed cases. Analysis showed that patients' age (χ²=10.640,=0.041); the time interval between onset and diagnosis (χ²=7.278, P=0.026); the source of cases (χ²=5.557, P=0.018); fever (χ²=5.676, P=0.014); dyspnea (χ²=113.085, P<0.001); muscle or joint pain (χ²=3.900, P=0.048); chest pain (χ²=13.446, P=0.006); the levels of lymphocytes (t=2.917, P=0.014), C-reactive protein (U=730.00, P<0.001), and aspartate aminotransferase (U=1235.00, P=0.002); damage in both lungs within 3 days of admission (χ²=7.632, P=0.003); and diabetes (χ²=6.675, P=0.010) were significantly correlated with the trend of intensification. CONCLUSIONS Older age, a long time interval from onset to diagnosis, imported cases from an affected area, dyspnea, muscle or joint pain, chest pain during the course of the disease, reduced lymphocytes, elevated C-reactive protein, computed tomography scan showing damage to both lungs within 3 days of admission, and diabetes mellitus are predictors for severe COVID-19.

Plasma Pharmacokinetic Determination of Canagliflozin and Its Metabolites in a Type 2 Diabetic Rat Model by UPLC-MS/MS.

Canagliflozin is a novel, orally selective inhibitor of sodium-dependent glucose co-transporter-2 (SGLT2) for the treatment of patients with type 2 diabetes mellitus. In this study, a sensitive and efficient UPLC-MS/MS method for the quantification of canagliflozin and its metabolites in rat plasma was established and applied to pharmacokinetics in a type 2 diabetic rat model. We firstly investigated the pharmacokinetic changes of canagliflozin and its metabolites in type 2 diabetic rats in order to use canagliflozin more safely, reasonably and effectively. We identified three types of O-glucuronide metabolites (M5, M7 and M17), two kinds of oxidation metabolites (M8 and M9) and one oxidation and glucuronide metabolite (M16) using API 5600 triple-TOF-MS/MS. Following liquid⁻liquid extraction by tert-butyl methyl ether, chromatographic separation of canagliflozin and its metabolites were performed on a Waters XBridge BEH C18 column (100 × 2.1 mm, 2.5 µm) using 0.1% acetonitrile⁻formic acid (75:15, v/v) as the mobile phase at a flow rate of 0.7 mL/min. Selected ion monitoring transitions of m/z 462.00→191.10, 451.20→153.10, 638.10→191.10 and 478.00→267.00 were chosen to quantify canagliflozin, empagliflozin (IS), O-glucuronide metabolites (M5, M7 and M17), and oxidation metabolites (M9) using an API 5500-triple-MS/MS in the positive electrospray ionization mode. The validation of the method was found to be of sufficient specificity, accuracy and precision. The pathological condition of diabetes could result in altered pharmacokinetic behaviors of canagliflozin and its metabolites. The pharmacokinetic parameters (AUC0⁻t, AUC0⁻∞, CLz/F, and Vz/F) of canagliflozin were significantly different between the CTRL and DM group rats (p < 0.05 or p < 0.01), which may subsequently cause different therapeutic effects.

Acute pneumonia due to Tropheryma whipplei diagnosed by metagenomic next-generation sequencing and pathology: A case report.

Tropheryma whipplei (TW) is a rod-shaped, gram-positive bacterium that, when chronically infects humans, can lead to multi-system pathologies, including joint pain, abdominal pain with diarrhea and weight loss, myocarditis, pericarditis, and neurologic inflammation. Moreover, acute infections can lead to bronchopulmonary infections, bacteraemia, and acute diarrhea. However, fewer cases of acute pneumonia due to TW have been reported, and this diagnosis is not well founded. Herein, we report a case of acute pneumonia caused by a TW infection. The patient, a middle-aged man, underwent bronchoscopic alveolar lavage, and the metagenomic next-generation sequencing of the lavage fluid suggested TW infection. A lung puncture biopsy tissue specimen was also positive based on periodic acid-Schiff staining. After confirming the diagnosis, the patient was administered ceftriaxone for anti-infection treatment, improving clinical symptoms and lung imaging results. Therefore, in cases where conventional anti-infective treatment is ineffective for patients with acute pneumonia, we should consider the possibility of TW infection, conduct prompt pathogenetic examination, and provide timely treatment after diagnosis to improve overall patient prognosis.

Drug-induced hypersensitivity syndrome related to piperacillin-tazobactam: a case report and review of the literature.

Allergic reactions to drugs caused by piperacillin-tazobactam are common in clinical practice. However, we also found a few cases of drug-induced hypersensitivity syndrome (DiHS)/Drug reaction with eosinophilia and systemic symptoms (DRESS) caused by piperacillin-tazobactam in our clinical work. We report a case of a 60-year-old female patient who was treated with piperacillin-tazobactam anti-infective therapy after the diagnosis of hematogenous lung abscess, developed fever, rash, and blood abnormalities after 26 days of application, and was later diagnosed as DIHS, which was improved after the administration of glucocorticoid and anti-allergic drugs. In addition, we also retrospectively analyzed 17 cases of DiHS caused by piperacillin-tazobactam from the PubMed databases between March 1980 and September 2023. The majority of the patients had an incubation period of more than 14 days, and the common clinical features included elevated eosinophil count/percentage, fever, rash, liver damage, and lymph node enlargement. After treatment with topical or systemic glucocorticoids, 16 of the 17 patients improved and one died because of the underlying condition. The clinical features of DiHS were diverse and included a long incubation period, skin rash, elevated eosinophils, and impaired organ function. Since some patients have atypical clinical features, clinicians should raise awareness of the disease, recognize these features early, and treat them promptly.

Clinical, Laboratory, and Imaging Characteristics of Tropheryma Whipplei Detection in Bronchoalveolar Lavage Fluid Using Next-Generation Sequencing: A Case-Control Study.

Objective: The aim of this study was to assess the prevalence of Tropheryma whipplei (TW) infection in the population and to investigate the clinical symptoms, as well as the laboratory and imaging characteristics of patients testing positive for TW using next-generation sequencing (NGS). Methods: A retrospective review was conducted on 1346 bronchoalveolar lavage fluid (BALF) samples collected between January 2021 and September 2023. The case group comprised patients with TW detected using NGS while the control group included 65 randomly chosen Gram-positive bacterial infection patients without TW. Comparative analyses were carried out on the basic demographics, laboratory parameters, and imaging findings between the two groups. Additionally, the case group underwent an in-depth examination of underlying diseases, pathogens, final diagnoses, treatment strategies. Results: The case group comprised of 51 patients with TW, constituting 3.8% of the total. There was no significant difference in gender and age between the case and control groups (P = 0.84, P = 0.07). Symptoms such as coughing, expectoration, wheezing, fever, and hemoptysis are less commonly detected in the case group with a higher incidence of chest pain when compared to the control group (P >0.05). The case group exhibited decreased albumin levels and increased C-reactive protein and D-dimer levels compared to normal levels. Imaging findings in the case group commonly included nodules, patchy images, and interstitial changes, the most common underlying disease is cardiovascular disease, and the most frequently co-occurring pathogen is the human herpesvirus. Among the case group, 27 patients received a final diagnosis of pneumonia, and 3 patients clinically diagnosed with Whipple's disease demonstrated improvement in both symptoms and imaging after treatment. Conclusion: NGS revealed a relatively low overall detection rate of TW-positive patients using BALF. TW was more prevalent in middle-aged and elderly male patients characterized by symptoms such as cough, expectoration, shortness of breath, and fever. Chest imaging in these cases typically showed nodules and interstitial changes.

ZEB1-activated Notch1 promotes circulating tumor cell migration and invasion in lung squamous cell carcinoma.

BACKGROUND: Lung squamous cell carcinoma (LUSC) is recognized as the major subtypes of non-small cell lung cancer (NSCLC). Circulating tumor cells (CTCs) are critical players in tumor metastasis. A molecular profiling of CTCs has previously identified notch receptor 1 (Notch1) as an important mediator in NSCLC. Therefore, we investigate Notch1 roles in LUSC and its related mechanisms. METHODS: The serum levels of Notch1 were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The CTCs isolated from blood samples were characterized via an immunofluorescence method. Cell motion was determined using Transwell chambers. The regulatory relationship between Notch1 and zinc finger E-box-binding homeobox 1 (ZEB1) was verified by chromatin immunoprecipitation (ChIP) and luciferase reporter assays. The protein levels were detected by western blotting. RESULTS: Higher Notch1 expression in patients with LUSC than that in normal controls was observed. Notch1 knockdown inhibited cell motion and epithelial-mesenchymal transition (EMT). ZEB1 transcriptionally activated Notch1. ZEB1 upregulation exacerbated the malignant phenotypes of CTCs. CONCLUSION: ZEB1-activated Notch1 promotes malignant phenotypes of CTCs in LUSC and indicates poor prognosis.

Differential Characteristics of Patients for Hospitalized Severe COVID-19 Infected by the Omicron Variants and Wild Type of SARS-CoV-2 in China.

Background: As multiple mutations of SARS-Cov-2 exist, there are now many viral variants with regional differences in distribution. The clinical characteristics of patients hospitalized with the virus also vary significantly, with those of the Omicron variants being strikingly different from those of the earliest wild-type variant. However, comprehensive data on this subject is lacking. It is therefore crucial to explore these differences to develop better clinical strategies for the management of COVID-19. Methods: A total of 554 confirmed COVID-19 cases in China were clinically classified as mild, moderate, severe, and critical according to their diagnoses and treatment plans. We compared the demographics and clinical characteristics of patients infected with the Omicron vs wild-type strains, between severe and non-severe cases. Bacterial co-infections with SARS-CoV-2 and correlation between inflammatory factors and T cells were analyzed. Results: Compared to the wild-type cases, the severe Omicron cases were older (median age 48.36 vs 73.24), and had more upper-respiratory symptoms and comorbidities. Decreased leukocyte counts were less pronounced, although more instances of significantly decreased CD4+ and CD8+ T-cell counts, elevated infection-related biomarkers (eg procalcitonin and C-reactive protein), and abnormal coagulation factors (including increased D-dimer and fibrinogen levels) were detected in the severe Omicron cases. The mean length of hospital stay was significantly shorter in the severe Omicron cases. CD4+ and CD8+ T cell numbers were negatively correlated with neutrophil-to-lymphocyte ratios, as well as serum interleukin-6, procalcitonin, and C-reactive protein levels. Conclusion: There were significant clinical differences between patients hospitalized with severe cases of Omicron- variant COVID-19 vs wild-type. The Omicron cases tended to be older and had more upper respiratory tract symptoms, comorbidities and bacterial co-infections. Elevated levels of inflammatory cytokines with T-cell depletion correlated with poor disease progression and prognosis. We hope these data provide a theoretical basis for future integrated prevention and control plans for COVID-19.

Vaccination increased host antiviral gene expression and reduced COVID-19 severity during the Omicron variant outbreak in Fuyang City, China.

BACKGROUND: The differences in host antiviral gene expression and disease severity between vaccinated and non-vaccinated coronavirus disease 2019 (COVID-19) patients are not well characterized. We sought to compare the clinical characteristics and host antiviral gene expression patterns of vaccinated and non-vaccinated cohorts at the Second People's Hospital of Fuyang City. METHODS: In this case-control study, we retrospectively analyzed 113 vaccinated patients with a COVID-19 Omicron variant infection, 46 non-vaccinated COVID-19 patients, and 24 healthy subjects (no history of COVID-19) recruited from the Second People's Hospital of Fuyang City. Blood samples were collected from each study participant for RNA extraction and PCR. We compared host antiviral gene expression profiles between healthy controls and COVID-19 patients who were either vaccinated or non-vaccinated at the time of infection. RESULTS: In the vaccinated group, most patients were asymptomatic, with only 42.9 % of patients developing fever. Notably, no patients had extrapulmonary organ damage. In contrast, 21.4 % of patients in the non-vaccinated group developed severe/critical (SC) disease and 78.6 % had mild/moderate (MM) disease, with fever occurring in 74.2 % patients. We found that Omicron infection in COVID-19 vaccinated patients was associated with significantly increased expression of several important host antiviral genes including IL12B, IL13, CXCL11, CXCL9, IFNA2, IFNA1, IFNγ, and TNFα. CONCLUSION: Vaccinated patients infected with the Omicron variant were mostly asymptomatic. In contrast, non-vaccinated patients frequently developed SC or MM disease. Older patients with SC COVID-19 also had a higher occurrence of mild liver dysfunction. Omicron infection in COVID-19 vaccinated patients was associated with the activation of key host antiviral genes and thus may play a role in reducing disease severity.

Respiratory Mucosal Immunity: Kinetics of Secretory Immunoglobulin A in Sputum and Throat Swabs From COVID-19 Patients and Vaccine Recipients.

While IgM and IgG response to SARS-CoV-2 has been extensively studied, relatively little is known about secretory IgA (sIgA) response in respiratory mucosa. Here we report IgA response to the SARS-CoV-2 in sputum, throat swabs, and serum with nucleocapsid protein (NP) enzyme-linked immunosorbent assays (ELISA) in a cohort of 28 COVID-19 patients and 55 vaccine recipients. The assays showed sIgA in respiratory mucosa could be detected on the first day after illness onset (AIO), and the median conversion time for sIgA in sputum, throat swabs, and serum was 3, 4, and 10 days, respectively. The positive rates of sIgA first week AIO were 100% (24/28) and 85.7% (24/28) in sputum and throat swabs, respectively, and were both 100% during the mid-onset (2-3 weeks AIO). During the recovery period, sIgA positive rates in sputum and throat swabs gradually decreased from 60.7% (17/28) and 57.1% (16/28) 1 month AIO and the sIgA antibodies were all undetectable 6 months AIO. However, serum IgA positive rate was still 100% at 4 months and 53.6% (15/28) at 6 months. Throat swabs obtained from volunteers who received inactivated SARS-CoV-2 vaccines by intramuscular delivery all showed negative results in IgA ELISA. These findings will likely improve our understanding of respiratory mucosal immunity of this emerging disease and help in containing the pandemic and developing vaccines.

Laboratory predictors of severe Coronavirus Disease 2019 and lung function in followed-up.

BACKGROUND: A pandemic caused by SARS-CoV-2 has infected more than 79 million people and killed exceeding 1.7 million people around the world by the end of 2020. METHOD: We obtained the clinical data of all diagnosed patients and lung function test of followed-up patients in Fuyang, Anhui province to investigate laboratory predictors of severe Coronavirus Disease 2019 (COVID-19) and the impairment of lung function. RESULTS: Of the 155 patients, 87 (56.13%) were males. The mean age was 41.95 (SD 15.34) years. Only 30 (19.35%) patients had the critical condition. Fever (84.52%) was the most common symptoms, and short of breath was more common in severe patients (p < 0.01). Lymphopenia was observed in most patients (74, 47.7%). It showed the elevation of CRP in 100 (64.5%) patients, the elevation of SAA or IL-6 in 104 (67.1%) patients. The calculated cut-off value of CRP was 19.35 mg/ml, the AUC was 0.777, sensitivity was 73.3%, specificity was 69.6%; SAA was 73.55 mg/L, 0.679, 83.3%, 56.8%, respectively; IL-6 was 18.85 pg/ml, 0.797, 83.3%, 64.8%; D-Dimer was 0.325 mg/L, 0.673, 66.7% and 68.8%. The combination of CRP, SAA, IL-6, and D-Dimer was 0.823 in AUC, 73.3% in sensitivity, and 78.4% in specificity. 12 (42.86%) followed-up patients had completely normal lung function indicators. CONCLUSION: Elevated CRP, SAA, IL-6 and D-Dimer can be predictors to severe COVID-19. The combination of these four indicators can improve the effectivity and specificity of assessing severe COVID-19. Most of the followed-up patients showed no abnormalities in lung function test. Abnormal lung function is mainly reflected in the diffusion function.

Assessment of Non-invasive Markers for the Prediction of Esophageal Variceal Hemorrhage.

Background: Esophageal variceal (EV) hemorrhage is a life-threatening consequence of portal hypertension in cirrhotic patients. Screening upper endoscopy and endoscopic variceal ligation to identify and treat EVs have contraindications, complications, and high costs. We sought to identify non-invasive tests (NITs) as alternatives to endoscopic EV screening. Methods: In this case-control study, we retrospectively analyzed 286 cirrhotic patients treated for EVs at the Second People's Hospital of Fuyang City, China from January to December 2019. We applied ROC curve analysis to assess the accuracy of various NITs in predicting EV hemorrhage. Results: There were significant differences between the hemorrhage and non-hemorrhage groups in median serum albumin (ALB) (p < 0.001), median bilirubin (TBIL) (p < 0.046), prothrombin (PT) time (p < 0.001), Golgi protein 73 (GP73; p = 0.012) and Child-Pugh (C-P) scores (p < 0.001). For ALB (cutoff <33.2g/L), PT time (cutoff > 14.2 seconds), GP73 (cutoff > 126.4 ng/ml), and C-P scores, the areas under the ROC curves (AUCs) were 73.4% (95% CI: 67.5-79.2), 68.6% (95% CI: 62.4-74.8), 62.2% (95% CI: 52.8-71.5) and 69.8% (95%CI: 63.8-75.8), respectively, with corresponding sensitives of 71.5, 59.8, 69.8, and 92.2% and specificities of 65.6%, 70.1%, 56.5%, and 38.6%. When ALB was combined with GP73, the AUC was 74.3% (95% CI: 66.1-82.5) with a sensitivity of 65.1% and specificity of 76.5%. When ALB, PT, and C-P scores were combined, the AUC was 76.5% (95% CI: 70.9-82.1) with a sensitivity of 79.5% and specificity of 64.3%. When ALB, PT, GP73, and C-P scores were combined, the AUC was 75.2% (95% CI: 67.3-83.1) with a sensitivity of 54.0% and specificity of 86.9%. Conclusion: ALB, TBIL, GP73, and C-P scores, may be used to predict EV hemorrhage in cirrhotic patients. The combination of multiple NITs is better than a single index and can increase diagnostic performance.

Efficient antiglioblastoma therapy in mice through doxorubicin-loaded nanomicelles modified using a novel brain-targeted RVG-15 peptide.

Glioblastoma (GBM) is an aggressive malignancy and therapeutic options are limited due to the presence of the blood-brain barrier (BBB). RVG-29, a 29-amino-acid polypeptide derived from the rabies virus glycoprotein (RVG), has excellent brain-targeted capacity across the BBB. We reduced the size of this peptide to get a15-amino-acid polypeptide (RVG-15), while retaining its brain-targeted capacity across the BBB. First, we synthesized a novel nanocarrier RVG-15-PEG2000-DSPE. Next, DOX-loaded polymeric micelles (DOX RVG-15-PMs) were prepared in an electrostatic interaction-dependent manner. Finally, we evaluated its antitumor benefits in vitro at the cellular level and in vivo using an in situ tumour-bearing mouse model. MALDI-TOF-MS and FTIR spectra confirmed the successful synthesis of the novel nanocarrier. The prepared DOX RVG-15-PMs displayed even size distribution, a high entrapment efficiency and satisfactory in vitro release behaviour. In vitro blank RVG-15-PMs were excellent, safe and highly biocompatible as drug delivery carriers. DOX-loaded micelles were easily taken up by C6 cells and could effectively inhibit cancer development and metastasis. In vivo, DOX RVG-15-PMs delayed weight loss, prevented cancer cell metastasis and accelerated cancer cell apoptosis in tumour-bearing mice. Our novel brain-targeted nanocarrier is highly feasible, while DOX RVG-15-PMs exert significant antiglioma effects, both in vitro and in vivo.

Differentially expressed immune response genes in COVID-19 patients based on disease severity.

BACKGROUND: Dysregulated immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are thought to underlie the progression of coronavirus disease 2019 (COVID-19). We sought to further characterize host antiviral and cytokine gene expression in COVID-19 patients based on illness severity. METHODS: In this case-control study, we retrospectively analyzed 46 recovered COVID-19 patients and 24 healthy subjects (no history of COVID-19) recruited from the Second People's Hospital of Fuyang City. Blood samples were collected from each study participant for RNA extraction and PCR. We assessed changes in antiviral gene expression between healthy controls and patients with mild/moderate (MM) and severe/critical (SC) disease. RESULTS: We found that type I interferon signaling (IFNA2, TLR8, IFNA1, IFNAR1, TLR9, IRF7, ISG15, APOBEC3G, and MX1) and genes encoding proinflammatory cytokines (IL12B, IL15, IL6, IL12A and IL1B) and chemokines (CXCL9, CXCL11 and CXCL10) were upregulated in patients with MM and SC disease. Moreover, we found that IFNA1, apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G (APOBEC3G), and Fas-associated protein with death domain (FADD) were significantly downregulated (P < 0.05) in the SC group compared to the MM group. We also observed that microRNA (miR)-155 and miR-130a levels were markedly higher in the MM group compared to the SC group. CONCLUSION: COVID-19 is associated with the activation of host antiviral genes. Induction of the IFN system appears to be particularly important in controlling SARS-CoV-2 infection, as decreased expression of IFNA1, APOBEC3G and FADD genes in SC patients, relative to MM patients, may be associated with disease progression.