Genetic diversity and evolutionary dynamics of Ebola virus in Sierra Leone.

A novel Ebola virus (EBOV) first identified in March 2014 has infected more than 25,000 people in West Africa, resulting in more than 10,000 deaths. Preliminary analyses of genome sequences of 81 EBOV collected from March to June 2014 from Guinea and Sierra Leone suggest that the 2014 EBOV originated from an independent transmission event from its natural reservoir followed by sustained human-to-human infections. It has been reported that the EBOV genome variation might have an effect on the efficacy of sequence-based virus detection and candidate therapeutics. However, only limited viral information has been available since July 2014, when the outbreak entered a rapid growth phase. Here we describe 175 full-length EBOV genome sequences from five severely stricken districts in Sierra Leone from 28 September to 11 November 2014. We found that the 2014 EBOV has become more phylogenetically and genetically diverse from July to November 2014, characterized by the emergence of multiple novel lineages. The substitution rate for the 2014 EBOV was estimated to be 1.23 × 10(-3) substitutions per site per year (95% highest posterior density interval, 1.04 × 10(-3) to 1.41 × 10(-3) substitutions per site per year), approximating to that observed between previous EBOV outbreaks. The sharp increase in genetic diversity of the 2014 EBOV warrants extensive EBOV surveillance in Sierra Leone, Guinea and Liberia to better understand the viral evolution and transmission dynamics of the ongoing outbreak. These data will facilitate the international efforts to develop vaccines and therapeutics.

Clinical and Virological Characteristics of Ebola Virus Disease Patients Treated With Favipiravir (T-705)-Sierra Leone, 2014.

BACKGROUND: During 2014-2015, an outbreak of Ebola virus disease (EVD) swept across parts of West Africa. No approved antiviral drugs are available for Ebola treatment currently. METHODS: A retrospective clinical case series was performed for EVD patients in Sierra Leone-China Friendship Hospital. Patients with confirmed EVD were sequentially enrolled and treated with either World Health Organization (WHO)-recommended supportive therapy (control group) from 10 to 30 October, or treated with WHO-recommended therapy plus favipiravir (T-705) from 1 to 10 November 2014. Survival and virological characteristics were observed for 85 patients in the control group and 39 in the T-705 treatment group. RESULTS: The overall survival rate in the T-705 treatment group was higher than that of the control group (56.4% [22/39] vs 35.3% [30/85]; P = .027). Among the 35 patients who finished all designed endpoint observations, the survival rate in the T-705 treatment group (64.8% [11/17]) was higher than that of the control group (27.8% [5/18]). Furthermore, the average survival time of the treatment group (46.9 ± 5.6 days) was longer than that of the control group (28.9 ± 4.7 days). Most symptoms of patients in the treatment group improved significantly. Additionally, 52.9% of patients who received T-705 had a >100-fold viral load reduction, compared with only 16.7% of patients in the control group. CONCLUSIONS: Treatment of EVD with T-705 was associated with prolonged survival and markedly reduced viral load, which makes a compelling case for further randomized controlled trials of T-705 for treating EVD.

Ebola Virus Outbreak Investigation, Sierra Leone, September 28-November 11, 2014.

During 2014-2015, an outbreak of Ebola virus disease (EVD) swept across parts of West Africa. The China Mobile Laboratory Testing Team was dispatched to support response efforts; during September 28-November 11, 2014, they conducted PCR testing on samples from 1,635 suspected EVD patients. Of those patients, 50.4% were positive, of whom 84.6% lived within a 3-km zone along main roads connecting rural towns and densely populated cities. The median time from symptom onset to testing was 5 days. At testing, 75.7% of the confirmed patients had fever, and 94.1% reported at least 1 gastrointestinal symptom; all symptoms, except rash and hemorrhage, were more frequent in confirmed than nonconfirmed patients. Virus loads were significantly higher in EVD patients with fever, diarrhea, fatigue, or headache. The case-fatality rate was lower among patients 15-44 years of age and with virus loads of <100,000 RNA copies/mL. These findings are key for optimizing EVD control and treatment measures.

Caspofungin for prophylaxis and treatment of fungal infections in adolescents and adults: a meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: Caspofungin, a novel echinocandin compound, has been approved for the treatment of esophageal and suspected invasive candidiasis and as salvage therapy for invasive aspergillosis. The aim of this study was to assess the efficacy and safety of caspofungin for the prophylaxis and treatment of fungal infections, compared with other medications. METHODS: PubMed, Embase, and the Cochrane Library were searched to identify relevant randomized controlled trials (RCTs) of caspofungin. Nine RCTs were included in this meta-analysis, performed using Review Manager Version 5.0. Analyses of favorable response, microbiological response, mortality rate, survival rate, relapse rate, and adverse events were performed to evaluate caspofungin. RESULTS: Caspofungin produced similar effects in favorable response rate [relative risk (RR) = 1.07, 95% confidence interval (CI) 0.98-1.17], microbiological response rate (RR = 1.02, 95%CI 0.90-1.15), mortality rate (RR = 0.98, 95%CI 0.78-1.24), survival rate after 7-day follow-up (RR = 1.00, 95% CI 0.91-1.10), and relapse rate (RR =1.18, 95% CI 0.81-1.73) compared with other antifungal agents in the prophylaxis and treatment of patients with fungal infections, particularly those caused by Candida. There were significant differences in clinical and laboratory adverse events between caspofungin and other antifungal agents in favor of caspofungin (RR = 0.66, 95% CI 0.49-0.89) (RR = 0.66, 95% CI 0.57-0.75). CONCLUSION: This meta-analysis shows that caspofungin can be used as effectively as other antifungal agents for prophylaxis and treatment of fungal infections, mainly for Candida, and that it is associated with fewer adverse effects than comparable agents.

Longitudinal Dynamics of Cellular Responses in Recovered COVID-19 Patients.

Safe and effective vaccines and therapeutics based on the understanding of antiviral immunity are urgently needed to end the COVID-19 pandemic. However, the understanding of these immune responses, especially cellular immune responses to SARS-CoV-2 infection, is limited. Here, we conducted a cohort study of COVID-19 patients who were followed and had blood collected to characterize the longitudinal dynamics of their cellular immune responses. Compared with healthy controls, the percentage of activation of SARS-CoV-2 S/N-specific T cells in recovered patients was significantly higher. And the activation percentage of S/N-specific CD8+ T cells in recovered patients was significantly higher than that of CD4+ T cells. Notably, SARS-CoV-2 specific T-cell responses were strongly biased toward the expression of Th1 cytokines, included the cytokines IFNγ, TNFα and IL2. Moreover, the secreted IFNγ and IL2 level in severe patients was higher than that in mild patients. Additionally, the number of IFNγ-secreting S-specific T cells in recovered patients were higher than that of N-specific T cells. Overall, the SARS-CoV-2 S/N-specific T-cell responses in recovered patients were strong, and virus-specific immunity was present until 14-16 weeks after symptom onset. Our work provides a basis for understanding the immune responses and pathogenesis of COVID-19. It also has implications for vaccine development and optimization and speeding up the licensing of the next generation of COVID-19 vaccines.

Clinical Analysis of Severe Radiation Pneumonia.

OBJECTIVE: The present study aims to discuss the clinical characteristics, factors, and treatment methods affecting the prognosis in patients with severe radiation pneumonia (RP). METHODS: The radiotherapy status, clinical features, imaging characteristics, laboratory examination results, treatment methods, and prognoses of 34 patients with severe RP treated in our department between January 2011 and July 2017 were retrospectively analyzed. The severe RP grading was based on the Common Terminology Criteria for Adverse Events version 4.0; patients who scored Grade ≥3 were considered to have a severe case of RP. RESULTS: The results of the present study showed that 22 patients had lung cancer, 6 had esophageal cancer, 5 had breast cancer, and 1 had colon cancer with lung metastasis. The total radiation dose was 37.5-66 Gy, and the overall average dose was 53 Gy; the average dose in the patients who died was 52.9 Gy. A total of 28 patients presented with a cough and sputum as the initial symptom, and 24 presented with wheezing as an accompanying symptom; of the 24 patients, 8 experienced fever, 2 experienced wheezing as the only symptom, 1 had chest pain, and 1 had chest tightness. In 26 patients, the changes were in the radiation field, and in 8 cases, the changes appeared both inside and outside the radiation field. After the use of glucocorticoid methylprednisolone, respiratory support, and anti-infection treatment, 18 patients were cured, 8 showed a condition improvement, and 8 died. CONCLUSION: The prognosis of severe RP was not significantly correlated with the administered radiation dose; however, lung cancer, a high Acute Physiology and Chronic Health Evaluation score, and delayed diagnosis were risk factors for patient death. However, a combination of antibiotic therapy, ventilator-assisted respiration, and steroid therapy could improve patient prognosis.

The effectiveness of adjustable oral appliance for older adult patients with obstructive sleep apnea syndrome.

BACKGROUND: Oral appliance (OA) treatment for obstructive sleep apnea syndrome (OSAS) has attracted more and more attention due to its low price, comfort, portable and non-invasion. This study aimed to investigate the clinical effectiveness of adjustable oral appliance on older adult patients with OSAS. METHODS: Thirty older adult patients diagnosed with OSAS were chosen as the study participants and received an adjustable OA for 6 months. Then, the patients were subjected to a polysomnographic examination, Berlin Questionnaire (BQ) scale questionnaire, and cone beam computer tomography (CBCT) analytical measurement to evaluate their symptom improvement and the morphologic changes of the upper airway. RESULTS: After treatment with adjustable oral appliance for six months, the results showed that there was an improvement of different degrees in the subjective symptoms. Apnea hypopnea index (AHI) had decreased from (27.65±1.31) per hour to (6.74±0.75) per hour (P<0.05); the maximum apnea time (MAT) had decreased from 43.82±2.69 to 21.37±3.18 s (P<0.05); the average oxygen saturation (MSaO2) had increased from (89.24±7.27)% to (92.69±4.46)%; the lowest oxygen saturation (LSaO2) from (81.85±8.31)% to (86.93±4.45)%. Moreover, the CBCT scanning analysis showed that the minimal sagittal diameter, sectional area, and the volume of the palatopharynx, as well as the sagittal diameter and volume of the glossopharynx significantly increased. CONCLUSIONS: The adjustable OA had considerable clinical efficacy and comfort in older adult OSAS patients by enlarging the palatopharynx and glossopharynx.

[Inhibitory effect of huangqi and dangshen extraction with pacilitaxel on metastasis and angiogenesis on mouse Lewis lung carcinoma model].

AIM: To study enhance effect of huangqi and dangshen extraction (Shenqi) on pacilitaxel inhibitory metastasis and angiogenesis on mouse Lewis lung carcinoma model. METHODS: Lewis lung carcinoma cells were inoculated into right hind footpad of C57BL/6 mice. Six hour after tumor inoculated, the mice were randomly divided into 3 groups.Shenqi (paclitaxel plus Shenqi) or paclitaxel was intraperitoneally injected in two group since the second day of the establishment of animal model. The third group simply administered with normal saline was set as placebo-control. Tumor volume, quantitation of microvessel density (MVD) in inoculated tumor, the number of metastasis in the lungs and survival analysis were compared in 3 groups. RESULTS: Paclitaxel plus Shenqi can effectively reduced MVD in inoculated tumor and the number of lung metastasis as compared with other two group (P<0.05). The survival time of Shenqi group was also significantly longer (P<0.05). Tumor volume was no statistical difference in three group (P>0.05). CONCLUSION: Shenqi can amplify the paclitaxel effect of anti-angiogenesis and anti-metastasis, enhances the survival time of mice bearing LLC, might has possible therapeutic applications in the treatment of lung cancer.

[Effect of huangqi and dangshen extraction on angiogenesis in Matrigel implant of mice].

AIM: To study the inhibitory effect of huangqi and dangshen extraction (SQ) on angiogenesis induced by b-FGF. METHODS: Matrigel implant assay was used. Matrigel(500 microL) containing b-FGF and heparin was injected subcutaneously into the abdomens of mice and harvested 5 d later. The amount of hemoglobin and micro-vascular area present in the implant were measured and compared. The mice were given different dosage of SQ (experimental group) or the same volume of glucose (vehicle group) once a day by intraperitoneal injection. Inhibitory experiment started 3 d before Matrigel implant and continued until the end of study. RESULTS: SQ in lower dosage (< or = 50% V/V) increased hemoglobin content and micro-vascular area in Matrigel implant while SQ in higher dosage (> or = 60%, V/V) reduced hemoglobin content and micro-vascular area in Matrigel implant. The effect of enhance ment and inhibition was in a limited concentration-effect manner. CONCLUSION: SQ in different dosage has different effects on angiogenesis. We should use different dosage in different purpose.

Comparative proteome analysis of serum from acute pulmonary embolism rat model for biomarker discovery.

Pulmonary embolism (PE) is a common, potentially fatal disease and its diagnosis is challenging because clinical signs and symptoms are nonspecific. In this study, to investigate protein alterations of a rat PE model, total serum proteins collected at different time points were separated by two-dimensional electrophoresis (2-DE) and identified using matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Bioinformatics analysis of 24 differentially expressed proteins showed that 20 had corresponding protein candidates in the database. According to their properties and obvious alterations after PE, changes of serum concentrations of Hp, Fn, DBP, RBP, and TTR were selected to be reidentified by western blot analysis. Semiquantitative RT-PCR showed DBP, RBP, and TTR to be down-regulated at mRNA levels in livers but not in lung tissues. The low serum concentrations of DBP, RBP, and TTR resulted in the up-regulation of 25(OH)D3, vitamin A, and FT4 (ligands of DBP, RBP, and TTR) after acute PE in rat models. The serum levels of Hp and Fn were detected in patients with DVT/PE and controls to explore their diagnostic prospects in acute PE because the mRNA levels of Hp and Fn were found to be up-regulated both in lung tissues and in livers after acute PE. Our data suggested that the concentration of serum Fn in controls was 79.42 +/- 31.57 microg/L, whereas that of PE/DVT patients was 554.43 +/- 136.18 microg/L (P < 0.001), and that the concentration of serum Hp in controls was 824.37 +/- 235.24 mg/L, whereas that of PE/DVT patients was 2063.48 +/- 425.38 mg/L (P < 0.001). The experimental PE rat model selected in this study was more similar to the clinical process than the other existing PE animal models, and the findings indicated instant changes of serum proteins within 48 h after acute PE. The exploration of these differentially expressed proteins or their combination with existent markers such as D-dimer may greatly improve the accuracy of the diagnosis of acute PE, but diagnostic tests are still needed to evaluate the sensitivity and specificity of these markers and also the number of false positives and false negatives.

[Cost analysis of Shenqi Fuzheng injection on reducing adverse effects during chemotherapy].

OBJECTIVE: The goals of this work was to analyse the cost of Shenqi Fuzheng injection-an extraction of a Chinese traditional herbs on reducing adverse effects in lung cancer patients during chemotherapy. METHODS: In a randomized cross-over trial, each patient completed two identical cisplatin-based chemotherapy cycles, one with Shenqi Fuzheng injection, another without Shenqi Fuzheng injection. Adverse effects and change scores of quality of life (QOL) during chemotherapy were compared in tow cycles. The direct cost dealing with adverse effect and cost-effectiveness analysis were taken. RESULTS: One hundred and thirty were enrolled with 123 of whom were evaluable. The patient characteristics were well balanced between the two groups. The chemotherapy cycles with Shenqi Fuzheng injection spent 220.5 more Chinese yuan, but the adverse effect of leukopenia, thrombocytopenia and vomiting were slight different and the change of score of several QOL domains showed significant better as compared to those in another cycle. CONCLUSION: Shenqi Fuzheng injection could reduce the severity of toxicity related to chemotherapy and improve the QOL of patients and had some benefits in terms of cost-effectiveness.