Clinical course and outcome of 107 patients infected with the novel coronavirus, SARS-CoV-2, discharged from two hospitals in Wuhan, China.

BACKGROUND: In December 2019, coronavirus disease 2019 (COVID-19) outbreak was reported from Wuhan, China. Information on the clinical course and prognosis of COVID-19 was not thoroughly described. We described the clinical courses and prognosis in COVID-19 patients. METHODS: Retrospective case series of COVID-19 patients from Zhongnan Hospital of Wuhan University in Wuhan and Xishui Hospital, Hubei Province, China, up to February 10, 2020. Epidemiological, demographic, and clinical data were collected. The clinical course of survivors and non-survivors were compared. Risk factors for death were analyzed. RESULTS: A total of 107 discharged patients with COVID-19 were enrolled. The clinical course of COVID-19 presented as a tri-phasic pattern. Week 1 after illness onset was characterized by fever, cough, dyspnea, lymphopenia, and radiological multi-lobar pulmonary infiltrates. In severe cases, thrombocytopenia, acute kidney injury, acute myocardial injury, and adult respiratory distress syndrome were observed. During week 2, in mild cases, fever, cough, and systemic symptoms began to resolve and platelet count rose to normal range, but lymphopenia persisted. In severe cases, leukocytosis, neutrophilia, and deteriorating multi-organ dysfunction were dominant. By week 3, mild cases had clinically resolved except for lymphopenia. However, severe cases showed persistent lymphopenia, severe acute respiratory dyspnea syndrome, refractory shock, anuric acute kidney injury, coagulopathy, thrombocytopenia, and death. Older age and male sex were independent risk factors for poor outcome of the illness. CONCLUSIONS: A period of 7-13 days after illness onset is the critical stage in the COVID-19 course. Age and male gender were independent risk factors for death of COVID-19.

Individualized active surveillance for carbapenem-resistant microorganisms using Xpert Carba-R in intensive care units.

Carbapenem antibiotics are widely used in ICU, and the prevalence of carbapenem-resistant microorganisms (CRO) has increased. This study aimed to assess the role of individualized active surveillance using Xpert Carba-R of carbapenem resistance genes on CRO risk. A total of 3,765 patients were admitted to the ICU of Zhongnan Hospital of Wuhan University between 2020 and 2022. The presence of carbapenem resistance genes were monitored using Xpert Carba-R, and CRO incidence was assigned as the investigated outcome. Of 3,765 patients, 390 manifested the presence of CRO, representing a prevalence of 10.36%. Active surveillance using Xpert Carba-R was associated with a lower CRO risk (odds ratio [OR]: 0.77; 95% confidence interval [CI] 0.62-0.95; P = 0.013), especially for carbapenem-resistant Acinetobacter + carbapenem-resistant Pseudomonas aeruginosa (OR: 0.79; 95% CI 0.62-0.99; P = 0.043), carbapenem-resistant Klebsiella pneumoniae (OR: 0.56; 95% CI 0.40-0.79; P = 0.001), and carbapenem-resistant Enterobacteriaceae (OR: 0.65; 95% CI 0.47-0.90; P = 0.008). Individualized active surveillance using Xpert Carba-R may be associated with a reduction in the overall CRO incidence in ICU. Further prospective studies should be performed to verify these conclusions and guide further management of patients in ICU.

Risk Factors for Mortality in 220 Patients With COVID-19 in Wuhan, China: A Single-Center, Retrospective Study.

BACKGROUND: An outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 infection occurred in Wuhan, China, in December 2019. To date, the analysis of fatal cases and the risk factors for death have rarely been reported. METHODS: In this study, 220 adult patients with confirmed and suspected COVID-19 were enrolled. Clinical characteristics, laboratory data, treatments, and complications were compared between 168 survivors and 52 nonsurvivors. Univariable analysis and multivariable logistic regression were used to investigate the risk factors for mortality. RESULTS: A total of 220 patients (168 were discharged and 52 died in the hospital) were enrolled in the study. The median age of all patients was 59.5 (47.0-69.0) years, and the median age of patients who died was significantly older than that of patients who survived (70.5 vs 56.0 years, respectively; P < .001). According to multivariate logistic regression, older age (odds ratio: 1.09, 95% CI: 1.03-1.15; P = .001), initial Sequential Organ Failure Assessment (SOFA) score >2 (37.4, 9.4-148.0; P = .011), and respiratory rate >24 per minute (10.89, 1.47-80.67; P = .019) were independent risk factors for mortality. CONCLUSION: Clinical and laboratory parameters predicting poor prognosis including older age, baseline SOFA score >2, and respiratory rate >24 per minute were identified.

Findings and Prognostic Value of Lung Ultrasonography in Coronal Virus Disease 2019 (COVID-19) Pneumonia.

PURPOSE: We used lung ultrasonography to identify features of COVID-19 pneumonia and to evaluate the prognostic value. PATIENTS AND METHODS: We performed lung ultrasonography on 48 COVID-19 patients in an intensive care unit (ICU) (Wuhan, China) using a 12-zone method. The associations between lung ultrasonography score, PaO2/FiO2, APACHE II, SOFA, and PaCO2 with 28-day mortality were analyzed and the receiver operator characteristic curve was plotted. RESULTS: 25.9% areas in all scanning zones presented with B7 lines and 23.5% with B3 lines (B-pattern) on lung ultrasonography; 13% areas with confluent B lines (B-pattern), 24.9% in areas with consolidations, and 9.9% in areas with A lines. Pleural effusion was observed in 2.8% of areas. Lung ultrasonography score was negatively correlated with PaO2/FiO2 (n = 48, r = -0.498, P < 0.05) and positively correlated with APACHE II (n = 48, r = 0.435, P < 0.05). Lung ultrasonography score was independently associated with 28-day mortality. The areas under receiver operator characteristic curves of lung ultrasonography score were 0.735 (95% CI: 0.586-0.844). The sensitivity, specificity, and cutoff values were 0.833, 0.722, and 22.5, respectively. CONCLUSIONS: Lung ultrasonography could be used to assess the severity of COVID-19 pneumonia, and it could also reveal the pathological signs of the disease. The lung ultrasonography score on ICU admission was independently related to the ICU 28-day mortality.

Clinical Course of 195 Critically Ill COVID-19 Patients: A Retrospective Multicenter Study.

INTRODUCTION: Coronavirus disease-2019 (COVID-19) outbreak has spread around the world. However, the dynamic course of critically ill COVID-19 has not been described thoroughly. PATIENTS AND METHODS: We retrospectively analyzed 195 critically ill COVID-19 patients in Hubei province, China, between January 5, 2020 and April 3, 2020. Epidemiologic data, clinical features, treatments, and outcomes were collected and analyzed. RESULTS: Most critically ill patients were older with higher Acute Physiology and Chronic Health Evaluation II scores. After critical illness onset, a total of 181 (92.8%) patients received ventilation support, of which 84 (43.1%) received noninvasive and 97 (49.7%) received invasive mechanic ventilation (IMV). Among the 97 patients with IMV, 28 (28.9%) received prone ventilation, 57 (58.8%) received neuromuscular blocked therapy, and 22 (11.3%) received tracheostomy due to prolonged ventilator use. Early hypoxemia, subsequent hypercapnia, pulmonary hypertension, and finally pulmonary fibrosis were notable in the clinical course of acute respiratory distress syndrome (ARDS). Eighty-nine (45.6%) patients presented with shock. Acute kidney injury (29.7%) and secondary infection (28.2%) were also notable. The overall mortality of critically ill patients at day 28 was 42.1%. Intensive care unit (ICU) mortality was around 33%, as 16 patients died prior to ICU admission. A low PaO2/FiO2 ratio was an independent risk factor for death. High viral load was observed in most non-survivors. CONCLUSION: ARDS and shock were notable in the critical illness of COVID-19. Ventilation support and hemodynamic support were the cornerstones for critical care. High viral load was associated with death of critically ill COVID-19 patients.

Antiferromagnetic Interfacial Coupling and Giant Magnetic Hysteresis in La0.5Ca0.5MnO3-SrRuO3 Superlattices.

Superlattices are of great importance due to their potential as new materials genome to synthesize new functional materials. Thus, tuning of the ground state of superlattices is crucial to further control their physical properties. In this study, superlattices (SLs) consisting of alternating layers of SrRuO3 (SRO) (5 nm) and La0.5Ca0.5MnO3 (LCMO) (5 nm) are epitaxially grown on SrTiO3 (STO) and LaAlO3 (LAO) substrates with 10-unit-cell periods. A variation in the substrate-induced-strain for this choice of SLs triggers observation of remarkable properties, such as magnetic anisotropy and large magnetic hysteresis. The strain states experienced by LCMO and SRO in these SLs result in strong ferromagnetic interlayer coupling and weak antiferromagnetic interlayer coupling at low temperatures in SLs of LCMO-SRO/STO and a strong antiferromagnetic interlayer coupling in SLs of LCMO-SRO/LAO. Besides, a large magnetic hysteresis resulting from the predominant magnetic anisotropy of SRO together with the strength of magnetic coupling is observed in SLs of LCMO-SRO/LAO along the out-of-plane direction of the LAO substrate. These four different magnetic behaviors along four different directions of substrate orientations are interpreted in terms of preferential orbital occupation and competing magnetic exchange coupling together with magnetic anisotropy. This study demonstrates the subtleties in controlling the strength of magnetic coupling at the interface and stands as a model system to realize fascinating magnetic phenomena in layer-by-layer hetero-epitaxial oxide films.

Knockdown of homeobox containing 1 increases the radiosensitivity of cervical cancer cells through telomere shortening.

Homeobox containing 1 (HMBOX1) modulates telomere length in various types of tumor cells by binding to double­stranded telomeric DNA. There is a negative correlation between telomere length and radiosensitivity in tumor cells. In the present study, we aimed to investigate the relationship among HMBOX1, telomere and radiosensitivity in cervical cancer cells. Lentivirus-based shRNAs were used to establish stable transfected cell lines in which protein and mRNA levels of HMBOX1 were notably decreased. Knockdown of HMBOX1 increased the radiosensitivity of HeLa and C33A cells. TERT protein was also decreased while HMBOX1 was downregulated. Knockdown of HMBOX1 shortened telomere length in the HeLa cells, while TERT overexpression rescued telomere shortening in the HeLa-HMBOX1 cells. Knockdown of HMBOX1 increased the apoptosis rate, decreased radiation-induced DNA damage foci, and inhibited the expression of ATM, ATR, p-ATM, p-ATR and BRCA1 in the homologous recombination repair pathway. Our data suggest a possible role of HMBOX1 in regulating radiosensitivity in cervical cancer cells. Moreover, HMBOX1 may be a potential factor in the radiotherapy of cervical cancer.

2-Methoxyestradiol enhances radiosensitivity in radioresistant melanoma MDA-MB-435R cells by regulating glycolysis via HIF-1α/PDK1 axis.

HIF-1α overexpression is associated with radio-resistance of various cancers. A radioresistant human melanoma cell model MDA-MB-435R (435R) was established by us previously. Compared with the parental cells MDA-MB­435 (435S), an elevated level of HIF-1α expression in 435R cells was demonstrated in our recent experiments. Therefore, in the current study, we sought to determine whether selective HIF-1α inhibitors could radiosensitize the 435R cells to X-ray, and to identify the potential mechanisms. Our data demonstrated that inhibition of HIF-1α with 2-methoxyestradiol (2-MeOE2) significantly enhanced radiosensitivity of 435R cells. 2-MeOE2 increased DNA damage and ratio of apoptosis cells induced by irradiation. Whereas, cell proliferation and the expression of pyruvate dehydrogenase kinase 1 (PDK1) were decreased after 2-MeOE2 treatment. The change of expression of GLUT1, LDHA and the cellular ATP level and extracellular lactate production indicates that 2-MeOE2 suppressed glycolytic state of 435R cells. In addition, the radioresistance, glycolytic state and cell proliferation of 435R cells were also decreased after inhibiting pyruvate dehydrogenase kinase 1 (PDK1) with dichloroacetate (DCA). DCA could also increase DNA damage and ratio of apoptotic cells induced by irradiation. These results also suggest that inhibition of HIF-1α with 2-MeOE2 sensitizes radioresistant melanoma cells 435R to X-ray irradiation through targeting the glycolysis that is regulated by PDK1. Selective inhibitors of HIF-1α and glycolysis are potential drugs to enhance radio-sensitivity of melanoma cells.

Identifying biomarkers of papillary renal cell carcinoma associated with pathological stage by weighted gene co-expression network analysis.

Although papillary renal cell carcinoma (PRCC) accounts for 10%-15% of renal cell carcinoma (RCC), no predictive molecular biomarker is currently applicable to guiding disease stage of PRCC patients. The mRNASeq data of PRCC and adjacent normal tissue in The Cancer Genome Atlas was analyzed to identify 1148 differentially expressed genes, on which weighted gene co-expression network analysis was performed. Then 11 co-expressed gene modules were identified. The highest association was found between blue module and pathological stage (r = 0.45) by Pearson's correlation analysis. Functional enrichment analysis revealed that biological processes of blue module focused on nuclear division, cell cycle phase, and spindle (all P < 1e-10). All 40 hub genes in blue module can distinguish localized (pathological stage I, II) from non-localized (pathological stage III, IV) PRCC (P < 0.01). A good molecular biomarker for pathological stage of RCC must be a prognostic gene in clinical practice. Survival analysis was performed to reversely validate if hub genes were associated with pathological stage. Survival analysis unveiled that all hub genes were associated with patient prognosis (P < 0.01).The validation cohort GSE2748 verified that 30 hub genes can differentiate localized from non-localized PRCC (P < 0.01), and 18 hub genes are prognosis-associated (P < 0.01).ROC curve indicated that the 17 hub genes exhibited excellent diagnostic efficiency for localized and non-localized PRCC (AUC > 0.7). These hub genes may serve as a biomarker and help to distinguish different pathological stages for PRCC patients.

UBE2D3 gene overexpression increases radiosensitivity of EC109 esophageal cancer cells in vitro and in vivo.

Ubiquitin-conjugating enzyme E2D3 (UBE2D3), a key component in ubiquitin (Ub) proteasome system, plays a crucial role in tumorigenesis. We previously found that it is bound to hTERT, and UBE2D3 could attenuate radiosensitivity of human breast cancer cells. Here we investigated a contributing role of UBE2D3 in radiosensitivity of esophageal squamous carcinoma. We demonstrated that the overexpression of UBE2D3 in esophageal squamous carcinoma cells (EC109) resulted in prolonged G1 phase and shortened G2/M phase after irradiation. UBE2D3 overexpression also decreased length of telomere and activity of telomerase. In addition, the overexpression of UBE2D3 increased mRNA expression but decreased protein levels of hTERT in both vitro and vivo systems. Compared with untreated cells, the treatment of UBE2D3 overexpressing cells with the specific proteasome inhibitor (MG132) could up-regulate hTERT. MG132 treatment of UBE2D3 overexpressed cells caused a clear and dramatic increase in the amount of ubiquitinated hTERT species. These findings indicate that UBE2D3 enhances radiosensitivity of EC109 cells by degradating hTERT through the ubiquitin proteolysis pathway.