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Current knowledge of the risk factors predicting the progression to severe coronavirus disease 2019 (COVID-19) among patients in community isolation who either are asymptomatic or only suffer from mild COVID-19 is very limited. Using a multivariable competing risk survival analysis, we herein identify several important predictors of progression to severe COVID-19—rather than to recovery—among patients in community isolation. A competing risk survival analysis was performed on time-to-event data from a cohort study of all COVID-19 patients (n = 1753) in the largest community isolation center in Wuhan, China, from opening to closing. The exposures were age, sex, respiratory symptoms, gastrointestinal symptoms, general symptoms, and computed tomography (CT) scan signs. The main outcomes were time to COVID-19 deterioration or recovery. The factors predicting progression to severe COVID-19 among the patients in community isolation were: male sex (hazard ratio (HR) = 1.29, 95% confidence interval (95%CI), 1.04–1.58, p = 0.018), young and old age, dyspnea (HR = 1.58, 95%CI, 1.24–2.01, p < 0.001), and CT signs of ground-glass opacity (HR = 1.39, 95%CI, 1.04–1.86, p = 0.024) and infiltrating shadows (HR= 1.84, 95%CI, 1.22–2.78, p = 0.004). The risk of progression was found to be lower among patients with nausea or vomiting (HR = 0.53, 95%CI, 0.30–0.96, p = 0.036) and headaches (HR = 0.54, 95%CI, 0.29–0.99, p = 0.046). Based on the results of this study, resource-poor settings, dyspnea, sex, and age can easily be used to identify mild COVID-19 patients who are at increased risk of progression. Looking for CT signs of ground-glass opacity and infiltrating shadows may be an affordable option to support triage decisions in resource-rich settings. Common and unspecific symptoms including headaches, nausea, and vomiting likely induced the selection for community isolation of COVID-19 patients who were relatively unlikely to deteriorate. Triage and prioritization outcomes could be boosted if strategies are incorporated to minimize the inefficient prioritization of harmless comorbidities.

BACKGROUND Consideration of the huge burden both of tuberculosis (TB) and diabetes mellitus (DM) in China as a major public health issue, research focused on the relationship between DM and TB was needed. METHODS An observational study was conducted (2015-2018) in regional representative TB and lung disease hospitals in China. All the adult patients newly diagnosed of pulmonary TB were consecutively recruited in this study. RESULTS A total of 1417 patients newly diagnosed pulmonary TB was recruited in this research, 312 (22.02%) of them had the history of type 2 DM. Majority of patients were with fatigue, loss of weight and mild anaemia in TB-DM group compared with TB-NDM group (58.3% vs 47.5%, p = .001; 8.21 ± 6.2 vs 5.74 ± 4.0 kg, p

Summary Background Wuhan was the epicentre of the COVID-19 outbreak in China. We aimed to determine the seroprevalence and kinetics of anti-SARS-CoV-2 antibodies at population level in Wuhan to inform the development of vaccination strategies. Methods In this longitudinal cross-sectional study, we used a multistage, population-stratified, cluster random sampling method to systematically select 100 communities from the 13 districts of Wuhan. Households were systematically selected from each community and all family members were invited to community health-care centres to participate. Eligible individuals were those who had lived in Wuhan for at least 14 days since Dec 1, 2019. All eligible participants who consented to participate completed a standardised electronic questionnaire of demographic and clinical questions and self-reported any symptoms associated with COVID-19 or previous diagnosis of COVID-19. A venous blood sample was taken for immunological testing on April 14–15, 2020. Blood samples were tested for the presence of pan-immunoglobulins, IgM, IgA, and IgG antibodies against SARS-CoV-2 nucleocapsid protein and neutralising antibodies were assessed. We did two successive follow-ups between June 11 and June 13, and between Oct 9 and Dec 5, 2020, at which blood samples were taken. Findings Of 4600 households randomly selected, 3599 families (78·2%) with 9702 individuals attended the baseline visit. 9542 individuals from 3556 families had sufficient samples for analyses. 532 (5·6%) of 9542 participants were positive for pan-immunoglobulins against SARS-CoV-2, with a baseline adjusted seroprevalence of 6·92% (95% CI 6·41–7·43) in the population. 437 (82·1%) of 532 participants who were positive for pan-immunoglobulins were asymptomatic. 69 (13·0%) of 532 individuals were positive for IgM antibodies, 84 (15·8%) were positive for IgA antibodies, 532 (100%) were positive for IgG antibodies, and 212 (39·8%) were positive for neutralising antibodies at baseline. The proportion of individuals who were positive for pan-immunoglobulins who had neutralising antibodies in April remained stable for the two follow-up visits (162 [44·6%] of 363 in June, 2020, and 187 [41·2%] of 454 in October–December, 2020). On the basis of data from 335 individuals who attended all three follow-up visits and who were positive for pan-immunoglobulins, neutralising antibody levels did not significantly decrease over the study period (median 1/5·6 [IQR 1/2·0 to 1/14·0] at baseline vs 1/5·6 [1/4·0 to 1/11·2] at first follow-up [p=1·0] and 1/6·3 [1/2·0 to 1/12·6] at second follow-up [p=0·29]). However, neutralising antibody titres were lower in asymptomatic individuals than in confirmed cases and symptomatic individuals. Although titres of IgG decreased over time, the proportion of individuals who had IgG antibodies did not decrease substantially (from 30 [100%] of 30 at baseline to 26 [89·7%] of 29 at second follow-up among confirmed cases, 65 [100%] of 65 at baseline to 58 [92·1%] of 63 at second follow-up among symptomatic individuals, and 437 [100%] of 437 at baseline to 329 [90·9%] of 362 at second follow-up among asymptomatic individuals). Interpretation 6·92% of a cross-sectional sample of the population of Wuhan developed antibodies against SARS-CoV-2, with 39·8% of this population seroconverting to have neutralising antibodies. Our durability data on humoral responses indicate that mass vaccination is needed to effect herd protection to prevent the resurgence of the epidemic. Funding Chinese Academy of Medical Sciences & Peking Union Medical College, National Natural Science Foundation, and Chinese Ministry of Science and Technology. Translation For the Chinese translation of the abstract see Supplementary Materials section.

A national and comprehensive evaluation is lacking on the relationship between short-term exposure to submicron particulate matter (PMData was obtained from 29,553 asthma deaths from the China National Mortality Surveillance System from 2015 to 2020. We used a bilinear interpolation approach to estimate each participant's daily ambient particulate matter pollution and meteorological variables exposure based on their geocoded residential address and a 10 km × 10 km grid from China High Air Pollutants and the fifth generation of European ReAnalysis-Land reanalysis data set. The associations were estimated using a time-stratified case-crossover design and conditional logistic regressions.Our results revealed significant associations between short-term exposure to various particulate matter and asthma mortality. The 5-day moving average of particulate matter exposure produced the most pronounced effect. Compared to fine particulate matter (PMOur study provided national evidence that acute exposures to various ambient particulate matter pollution can increase mortality due to asthma in China, highlighting stronger associations with ambient PM

Background: Asthma is a chronic airway disorder associated with aberrant inflammatory, remodeling and angiogenesis, indicating that the altered pulmonary microcirculatory may exist in the local and contribute to the pathogenesis. There are rare studies in vivo, which could directly prove the disorders of microcirculation in asthmatic lungs. This study aimed to establish Micro-in-One platform and set up the first profile of the integrated asthmatic pulmonary microcirculation. Methods: Using murine models of asthma induced by ovalbumin (OVA) and house dust mite (HDM), the raw data set of pulmonary microcirculation was collected and visualized by multimodal device and computer algorithm-based Micro-in-One platform. A three-dimensional framework was constructed, and changes of pulmonary microcirculatory oxygen, microhemodynamics were compared. The contributions of biological oscillators were revealed by wavelet transform analysis. Additionally, levels of microcirculation-associated proteins in serum were measured by antibody-pair-based assay. Results: Microcirculatory profile of the lungs in both OVA-induced and HDM-induced asthma groups exhibited a loss of microhemodynamic coherence compare to the control mice, including the decreased microvascular blood perfusion, decreased PO , and significantly increased index of pulmonary microcirculatory resistance (IMRp). In addition, amplitude regimens separated by (NO-dependent and NO-independent) endothelial components were related to the changes in pulmonary microcirculation in asthmatic models. Meanwhile, matrix-based hierarchical clustering analysis showed that IMRp positively correlated to amplitude in both asthmatic groups. Conclusions: Micro-in-One is a validated and reliable method to measure and visualize the integrated pulmonary microcirculation. Data suggest that there is the dysfunctional status of pulmonary microcirculation in asthma.

Background Since the outbreak of coronavirus disease 2019 (COVID‐19), clinical features have been analyzed in detail. However, coagulopathy in elderly COVID‐19 patients has been scarcely reported. Methods Coagulation parameters of 189 patients with COVID‐19 in Tongji hospital were retrospectively analyzed among age groups. Results Patients were divided into 2 groups: older group (≥65 years, n = 87) and younger group (, In this study, we summarized the characteristics of coagulopathy in different age groups with SARS‐CoV‐2 infection, and investigated the relations between coagulopathy and systemic inflammation in COVID‐19 patients.

Coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has become a worldwide pandemic since it emerged in December, 2019. Previous studies have reported rapid antibody response to SARS‐CoV‐2 with the first 2‐3 weeks after symptom onset. Here, we retrospectively described the dynamic changes of serum IgM and IgG specifically against SARS‐CoV‐2 in later weeks (mainly 4‐10 weeks) in 97 hospitalized patients with COVID‐19. We observed that serum IgM and IgG, especially in patients with moderate‐to‐high levels, declined significantly between week 4‐10 after illness onset. Notably, IgG levels in high percentage of patients (77.5%, 31/40) rapidly declined by half, from 212.5 (range, 163.7‐420.3) to 96.3 (range, 75.0‐133.4) AU/ml, within 1‐2 weeks in the second month and then sustained around 100 AU/ml until discharge from hospital. Significant reduction of IgM was also observed as SARS‐CoV‐2 nucleic acid converted to negative (p=0.002). In the recovery stage, serum IgG declined significantly (early vs. late recovery stage, n=16, p=0.003) with a median reduction of 50.0% (range, 3.7‐77.0%). Our results suggested the decline of IgM may be an indicator of virus clearance and recovery patients may have robust immunity against reinfection within at least 3 months after illness onset. Yet, the rapid reduction of IgG by half arises serious concerns on the robustness and sustainability of humoral immune response in the future period after discharge, which is crucial for immunity strategy and developing vaccine. This article is protected by copyright. All rights reserved.

Introduction Xiyanping injection (XYP), a type of Traditional Chinese Medicine, is often applied in combination with other medications in treating bronchitis, tonsillitis, and bacillary dysentery in China, which is evidently associative with allergic reactions. In recent years, XYP’s adverse drug reactions (ADRs), represented by allergic reactions, have emerged throughout the country.Objective This study aims to investigate the association between the concomitant use of XYP and 25 most frequently co-applied medications with suspected allergic reactions for China’s patients receiving XYP.Methods A nested case-control study was conducted using the sampling data from 2015 China’s Urban Employees Basic Medical Insurance and Urban Residents Basic Medical Insurance database. Four anti-allergic marker drugs were used to evaluate suspected allergic reactions. Univariate analyses and multivariable conditional logistic regression were conducted, and results were reported as odds ratios (ORs) with 95% confidence interval (CI). Sensitivity analyses were performed on the expanded sample by including those prescribed with anti-allergic marker drugs on the same day as XYP and then stopped XYP on the next day.Results Out of 57,612 participants with XYP prescription, we got 949 matched case-control pairs. Multivariable conditional logistic regression revealed that seven concomitant medications including gentamicin (OR = 4.3; 95% CI [2.5, 7.3]), cefoperazone-sulbactam (OR = 4.3; 95% CI [1.4, 13.0]), lidocaine (OR = 2.8; 95% CI [1.8, 4.2]), aminophylline (OR = 1.7; 95% CI [1.1, 2.9]), ribavirin (OR = 1.5; 95% CI [1.1, 2.1)), potassium chloride (OR = 1.4; 95% CI [1.1, 1.9]), and vitamin C (OR = 1.3; 95% CI [1.0, 1.7]) were associated with increased risk, while cefathiamidine (OR = 0.3; 95% CI [0.2, 0.5]) was associated with reduced risk. Sensitivity analysis on 2,438 matched pairs revealed similar findings. Conclusion Increased risks for suspected allergic reactions were found for the concomitant use of XYP with seven medications. Our data suggest that gentamicin, cefoperazone-sulbactam, lidocaine and ribavirin should be applied with precautions for patients receiving XYP, and further studies on drug interactions and allergy mechanisms are warranted.

Background Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that rapidly spreads worldwide and co-infection of COVID-19 and influenza may occur in some cases. We aimed to describe clinical features and outcomes of severe COVID-19 patients with co-infection of influenza virus. Methods Retrospective cohort study was performed and a total of 140 patients with severe COVID-19 were enrolled in designated wards of Sino-French New City Branch of Tongji Hospital between Feb 8th and March 15th in Wuhan city, Hubei province, China. The demographic, clinical features, laboratory indices, treatment and outcomes of these patients were collected. Results Of 140 severe COVID-19 hospitalized patients, including 73 patients (52.14%) with median age 62 years were influenza virus IgM-positive and 67 patients (47.86%) with median age 66 years were influenza virus IgM-negative. 76 (54.4%) of severe COVID-19 patients were males. Chronic comorbidities consisting mainly of hypertension (45.3%), diabetes (15.8%), chronic respiratory disease (7.2%), cardiovascular disease (5.8%), malignancy (4.3%) and chronic kidney disease (2.2%). Clinical features, including fever (≥38 °C), chill, cough, chest pain, dyspnea, diarrhea and fatigue or myalgia were collected. Fatigue or myalgia was less found in COVID-19 patients with IgM-positive (33.3% vs 50/7%, P = 0.0375). Higher proportion of prolonged activated partial thromboplastin time (APTT) > 42 s was observed in COVID-19 patients with influenza virus IgM-negative (43.8% vs 23.6%, P = 0.0127). Severe COVID-19 Patients with influenza virus IgM positive have a higher cumulative survivor rate than that of patients with influenza virus IgM negative (Log-rank P = 0.0308). Considering age is a potential confounding variable, difference in age was adjusted between different influenza virus IgM status groups, the HR was 0.29 (95% CI, 0.081–1.100). Similarly, difference in gender was adjusted as above, the HR was 0.262 (95% CI, 0.072–0.952) in the COX regression model. Conclusions Influenza virus IgM positive may be associated with decreasing in-hospital death.

Additional file 2: Supplementary Table 2. Clinical Characteristics, treatment and prognosis of COVID-19 Patients by death and influenza IgM+/−

Additional file 1: Supplementary Table 1. Clinical Characteristics of COVID-19 Patients by death or discharge

Background Coronavirus disease 2019 (COVID-19) is an emerging infection disease that rapidly spreads worldwide. Co-infection may occur in some cases of COVID-19, like influenza virus and so on. Clinical features and outcomes of severe COVID-19 patients with co-infection of influenza virus need to be noticed.Methods Retrospective cohort study was performed and total of 140 patients with severe COVID-19 was enrolled in designated wards of Sino-French New City Branch of Tongji Hospital between Feb 8th and March 15th in Wuhan, Hubei province, China. The demographic, clinical features, laboratory indices, treatment and outcomes of these patients were collected and analyzed.Results Of 140 severe COVID-19 hospitalized patients, 73 patients were with median age of 66 years old with identification of influenza virus IgM-positive and 67 patients were with median age of 62 years old in influenza virus IgM-negative. Nearly half of severe COVID-19 patients in this research are male. Majority of the severe COVID-19 patients had chronic underlying conditions. Wheeze was the clinical feature of severe COVID-19 patients with influenza IgM-positive (26.4% vs 9.0%, P = 0.008). On contrary, fatigue or myalgia was the feature of the COVID-19 patients without IgM-positive (38.4% vs 58.2%, P = 0.019). Increased levels of ferritin and prolonging APTT were showed in severe COVID-19 patients without influenza IgM-positive compared with patients in other group with significant differences. Death rate in the group of severe COVID-19 patients with influenza IgM-positive is lower than it in other group with significant differences (4.1% vs 14.9%, P = 0.040). In univariate regression analysis, several factors were associated with higher risk of death, which included LDH, troponin, NT-proBNP, D-dimer, PT, APTT, lymphocytes, platelet and eGFR. However, influenza virus IgM positive was associated with lower risk of death.Conclusions Characteristic features of patients with severe COVID-19 with influenza virus IgM-positive were described. Co-infection may occur during the pandemic of COVID-19, and we need to improve our understanding in order to confront this crisis in the future.

Importance Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19), but further data from randomized clinical trials are needed. Objective To evaluate the efficacy and adverse effects of convalescent plasma therapy for patients with COVID-19. Design, Setting, and Participants Open-label, multicenter, randomized clinical trial performed in 7 medical centers in Wuhan, China, from February 14, 2020, to April 1, 2020, with final follow-up April 28, 2020. The trial included 103 participants with laboratory-confirmed COVID-19 that was severe (respiratory distress and/or hypoxemia) or life-threatening (shock, organ failure, or requiring mechanical ventilation). The trial was terminated early after 103 of a planned 200 patients were enrolled. Intervention Convalescent plasma in addition to standard treatment (n = 52) vs standard treatment alone (control) (n = 51), stratified by disease severity. Main Outcomes and Measures Primary outcome was time to clinical improvement within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale (ranging from 1 [discharge] to 6 [death]). Secondary outcomes included 28-day mortality, time to discharge, and the rate of viral polymerase chain reaction (PCR) results turned from positive at baseline to negative at up to 72 hours. Results Of 103 patients who were randomized (median age, 70 years; 60 [58.3%] male), 101 (98.1%) completed the trial. Clinical improvement occurred within 28 days in 51.9% (27/52) of the convalescent plasma group vs 43.1% (22/51) in the control group (difference, 8.8% [95% CI, −10.4% to 28.0%]; hazard ratio [HR], 1.40 [95% CI, 0.79-2.49];P = .26). Among those with severe disease, the primary outcome occurred in 91.3% (21/23) of the convalescent plasma group vs 68.2% (15/22) of the control group (HR, 2.15 [95% CI, 1.07-4.32];P = .03); among those with life-threatening disease the primary outcome occurred in 20.7% (6/29) of the convalescent plasma group vs 24.1% (7/29) of the control group (HR, 0.88 [95% CI, 0.30-2.63];P = .83) (Pfor interaction = .17). There was no significant difference in 28-day mortality (15.7% vs 24.0%; OR, 0.59 [95% CI, 0.22-1.59];P = .30) or time from randomization to discharge (51.0% vs 36.0% discharged by day 28; HR, 1.61 [95% CI, 0.88-2.95];P = .12). Convalescent plasma treatment was associated with a negative conversion rate of viral PCR at 72 hours in 87.2% of the convalescent plasma group vs 37.5% of the control group (OR, 11.39 [95% CI, 3.91-33.18];P Conclusion and Relevance Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment, compared with standard treatment alone, did not result in a statistically significant improvement in time to clinical improvement within 28 days. Interpretation is limited by early termination of the trial, which may have been underpowered to detect a clinically important difference. Trial Registration Chinese Clinical Trial Registry:ChiCTR2000029757

Background The lack of effective treatments against the 2019 coronavirus disease (COVID-19) has led to the exploratory use of convalescent plasma for treating COVID-19. Case reports and case series have shown encouraging results. This study investigated SARS-CoV-2 antibodies and epidemiological characteristics in convalescent plasma donors, to identify criteria for donor selection. Methods Recovered COVID-19 patients, aged 18-55 years, who had experienced no symptoms for more than 2 weeks, were recruited. Donor characteristics such as disease presentations were collected and SARS-CoV-2 N-specific IgM, IgG, and S-RBD-specific IgG levels were measured by enzyme-linked immunosorbent assay (ELISA). Results Whereas levels of N-specific IgM antibody declined after recovery, S-RBD-specific and N-specific IgG antibodies increased after 4 weeks from the onset of symptoms, with no significant correlation to age, sex, or ABO blood type. Donors with the disease presentation of fever exceeding 38.5°C or lasting longer than 3 days exhibited higher levels of S-RBD-specific IgG antibodies at the time of donation. Of the 49 convalescent plasma donors, 90% had an S-RBD-specific IgG titer of ≥1:160 and 78% had a titer of ≥1:640 at the time of plasma donation. Of the 30 convalescent plasma donors, who had donated plasma later than 28 days after the onset of symptoms and had a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5°C, 100% had an S-RBD-specific IgG titer of ≥1:160 and 93% had a titer of ≥1:640. Conclusion This study indicates that the S-RBD-specific IgG antibody reaches higher levels after 4 weeks from the onset of COVID-19 symptoms. We recommend the following selection criteria for optimal donation of COVID-19 convalescent plasma: 28 days after the onset of symptoms and with a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5°C. Selection based on these criteria can ensure a high likelihood of achieving sufficiently high S-RBD-specific IgG titers.

Summary Background Small airway dysfunction is a common but neglected respiratory abnormality. Little is known about its prevalence, risk factors, and prognostic factors in China or anywhere else in the world. We aimed to estimate the prevalence of small airway dysfunction using spirometry before and after bronchodilation, both overall and in specific population subgroups; assess its association with a range of lifestyle and environmental factors (particularly smoking); and estimate the burden of small airway dysfunction in China. Methods From June, 2012, to May, 2015, the nationally representative China Pulmonary Health study invited 57 779 adults to participate using a multistage stratified sampling method from ten provinces (or equivalent), and 50 479 patients with valid lung function testing results were included in the analysis. We diagnosed small airway dysfunction on the basis of at least two of the following three indicators of lung function being less than 65% of predicted: maximal mid-expiratory flow, forced expiratory flow (FEF) 50%, and FEF 75%. Small airway dysfunction was further categorised into pre-small airway dysfunction (defined as having normal FEV1 and FEV1/forced vital capacity [FVC] ratio before bronchodilator inhalation), and post-small airway dysfunction (defined as having normal FEV1 and FEV1/FVC ratio both before and after bronchodilator inhalation). Logistic regression yielded adjusted odds ratios (ORs) for small airway dysfunction associated with smoking and other lifestyle and environmental factors. We further estimated the total number of cases of small airway dysfunction in China by applying present study findings to national census data. Findings Overall the prevalence of small airway dysfunction was 43·5% (95% CI 40·7–46·3), pre-small airway dysfunction was 25·5% (23·6–27·5), and post-small airway dysfunction was 11·3% (10·3–12·5). After multifactor regression analysis, the risk of small airway dysfunction was significantly associated with age, gender, urbanisation, education level, cigarette smoking, passive smoking, biomass use, exposure to high particulate matter with a diameter less than 2·5 μm (PM2·5) concentrations, history of chronic cough during childhood, history of childhood pneumonia or bronchitis, parental history of respiratory diseases, and increase of body-mass index (BMI) by 5 kg/m2. The ORs for small airway dysfunction and pre-small airway dysfunction were similar, whereas larger effect sizes were generally seen for post-small airway dysfunction than for either small airway dysfunction or pre-small airway dysfunction. For post-small airway dysfunction, cigarette smoking, exposure to PM2·5, and increase of BMI by 5 kg/m2 were significantly associated with increased risk, among preventable risk factors. There was also a dose-response association between cigarette smoking and post-small airway dysfunction among men, but not among women. We estimate that, in 2015, 426 (95% CI 411–468) million adults had small airway dysfunction, 253 (238–278) million had pre-small airway dysfunction, and 111 (104–126) million had post-small airway dysfunction in China. Interpretation In China, spirometry-defined small airway dysfunction is highly prevalent, with cigarette smoking being a major modifiable risk factor, along with PM2·5 exposure and increase of BMI by 5 kg/m2. Our findings emphasise the urgent need to develop and implement effective primary and secondary prevention strategies to reduce the burden of this condition in the general population. Funding Ministry of Science and Technology of China; National Natural Science Foundation of China; National Health Commission of China.

Background: Invasive mycoses are serious infections with high mortality and increasing inci-dence. Voriconazole, an important drug to treat invasive mycosis, is metabolized mainly by the cytochrome P450 family 2 subfamily C member 19 enzyme (CYP2C19) and is affected by the genotypes of CYP2C19. Objective: We reviewed studies on how genotypes affect the pharmacokinetics and pharmacodynamics of voriconazole, and attempted to determine a method to decide on dosage adjustments based on genotypes, after which, the main characteristic of voriconazole was clarified in details. The pharmacokinetics of voriconazole are influenced by various inter and intrapersonal factors, and for certain populations, such as geriatric patients and pediatric patients, these influences must be considered. CYP2C19 genotype represents the main part of the interpersonal variability related to voriconazole blood concentrations. Thus monitoring the concentration of voriconazole is needed in clinical scenarios to minimize the negative influences of inter and intrapersonal factors. Several studies provided evidence on the stable trough concentration range from 1-2 to 4-6 mg/L, which was combined to consider the efficacy and toxicity. However, the therapeutic drug concentration needs to be narrowed down and evaluated by large-scale clinical trials. Conclusion: Though there is insufficient evidence on the relationship between CYP2C19 genotypes and clinical outcomes, there is a great potential for the initial voriconazole dose selection to be guided by the CYP2C19 genotype. Finally, voriconazole therapeutic drug monitoring is essential to provide patient-specific dosing recommendations, leading to more effective anti-fungal regimens to increase clinical effica-cy and reduce adverse drug reactions.

OBJECTIVE To evaluate the genetic association between rs16969968 and lung cancer risk by meta-analysis. DATA SOURCE We searched eligible studies from MEDLINE, Web of Science and EMBASE up to Dec, 2017. STUDY SELECTION Association studies concerning rs16969968 and lung cancer risk were included. We assessed the association strength between this polymorphism and risk of lung cancer by calculating odds ratios (OR) and 95% confidence interval (95%CI). RESULTS A total of 26 data sets comprising 30 772 lung cancers and 90 954 controls were included. rs16969968 was found to be associated with lung cancer risk in population of European ancestry in all models (A vs. G: OR = 1.30, 95%CI 1.27-1.33, P

The protective effect of high-density lipoprotein (HDL) on endothelial function is impaired in patients with type 2 diabetes mellitus (T2DM), which may result in atherosclerotic complications. Naoxintong (NXT) is a compound preparation that includes Radix Astragali, Angelicae sinensis, Radix Paeoniae Rubra and Ligusticum wallichii. It is widely administered in China to prevent atherosclerotic complications. In the present study, NXT was administered to 69 patients with T2DM. HDLs were isolated from patient blood samples prior to and following the intervention. In vitro endothelial functions of HDL, including proliferation, migration, angiogenesis, and anti-apoptosis were investigated by bromodeoxyuridine, wound healing, Transwell and Matrigel tube formation assays on human umbilical vein endothelial cells (HUVECs). The results from the present study demonstrated that HUVECs treated with HDL isolated from diabetic patients following NXT therapy exhibited increased proliferative effects (10–27%; P

Table S1. Detection of pathogenic bacteria and other fungi. (DOCX 14Â kb)

Background Recently awareness of the importance of Aspergillus colonization in the airway of patients with chronic obstructive pulmonary disease (COPD) was rising. The aim of this study was to investigate the clinical features and short-term outcomes of COPD patients with Aspergillus colonization during acute exacerbation. Methods A pair-matched retrospective study on patients presenting with COPD exacerbation was conducted from January 2014 to March 2016 in Beijing Hospital, China. Results Twenty-three patients with Aspergillus colonization and 69 patients as controls, diagnosed of COPD exacerbation, were included in this study at a pair-matched ratio of 1:3. In stable stage, the percentage of patients with high-dose corticosteroids inhalation in the Aspergillus colonization group is higher than that of in control group (65.5% vs 33.3%, p = 0.048). Multivariate analysis showed that corticosteroids use was the risk factor for isolation of Aspergillus. In acute exacerbation stage, patients in Aspergillus colonization group received higher dose of inhaled corticosteroids and more types of antibiotics than control group. The short-time outcome hinted that the remission time and the duration of hospitalization were longer in the Aspergillus colonization group than in the control group (remission time: 11 ± 4 days vs 7 ± 4 days, p = 0.001; duration: 15 ± 5 days vs 12 ± 4 days, p = 0.011). Conclusions Aspergillus colonization in the lower respiratory tract of COPD patients showed typical clinical manifestations, affected their short time outcome and provided a dilemma of clinical treatment strategy. Electronic supplementary material The online version of this article (10.1186/s12890-018-0611-y) contains supplementary material, which is available to authorized users.

Invasive fungal infections acquired in the hospital have progressively emerged as an important cause of life-threatening infection. In particular, airborne fungi in hospitals are considered critical pathogens of hospital-associated infections. To identify the causative airborne microorganisms, high-volume air samplers were utilized for collection, and species identification was performed using a culture-based method and DNA sequencing analysis with the Illumina MiSeq and HiSeq 2000 sequencing systems. Few bacteria were grown after cultivation in blood agar. However, using microbiome sequencing, the relative abundance of fungi, Archaea species, bacteria and viruses was determined. The distribution characteristics of fungi were investigated using heat map analysis of four departments, including the Respiratory Intensive Care Unit, Intensive Care Unit, Emergency Room and Outpatient Department. The prevalence of Aspergillus among fungi was the highest at the species level, approximately 17% to 61%, and the prevalence of Aspergillus fumigatus among Aspergillus species was from 34% to 50% in the four departments. Draft genomes of microorganisms isolated from the hospital environment were obtained by sequence analysis, indicating that investigation into the diversity of airborne fungi may provide reliable results for hospital infection control and surveillance.

Mycobacterium kansasii is the second most common cause of slowly growing non-tuberculous mycobacteria diseases in China. The aim of the present study was to analyze M. kansasii subtypes isolated from patients in China, and to explore the antimicrobial susceptibility of the differentiation among these diverse subtypes. A total of 78 M. kansasii strains from 16 provinces of China were enrolled in this study. Amikacin (AMK) was the most highly active against M. kansasii strains, and only 4 isolates (5.1%) exhibited in vitro resistance to AMK. The percentage of levofloxacin (LFX) resistant strains among the 78 M. kansasii isolates was 39.7% (31/78), which was significantly higher than that of moxifloxacin (16.7%, P = 0.001) and gatifloxacin (19.2%, P = 0.005). By using PCR-restriction fragment analysis of the hsp65 gene (PRA), all the isolates were classified as four different subtypes. Of these four subtypes, M. kansasii subtype I was the most frequent genotype in China, accounting for 71.8% (56/78) of M. kansasii isolates. Resistance to clarithromycin (CLA) was noted in 26.8% (15/56) of subtype I isolates, which was significant higher than that of other subtypes (4.5%, P = 0.031). DNA sequencing revealed that the presence of mutations in 23S rRNA was associated with 56.2% (9/16) of CLA-resistant M. kansasii isolates. In conclusion, our data demonstrate that AMK is the most active agent against M. kansasii in vitro, while the high proportion of CLA resistance is noted in M. kansasii isolates. In addition, the predominant subtype I is associated with CLA resistance in China.

Sphingosine kinases (SphKs) catalyze the conversion of the sphingosine to the promitogenic/migratory product, sphingosine-1-phosphate (S1P). SphK/S1P pathway has been linked to the progression of cancer and various other diseases including allergic inflammatory disease, cardiovascular diseases, rejection after transplantation, the central nervous system, and virus infections. Therefore, SphKs represent potential new targets for developing novel therapeutics for these diseases. The history and development of SphK inhibitors are discussed, summarizing SphK inhibitors by their structures, and describing some applications of SphK inhibitors. We concluded: i) initial SphK inhibitors based on sphingosine have low specificity with several important off-targets. Identification the off-targets that would work synergistically with SphKs, and developing compounds that target the unique C4 domain of SphKs should be the focus of future studies. ii) The modifications of SphK inhibitors, which are devoted to increasing the selectivity to one of the two isoforms, now focus on the alkyl length, the spacer between the head and linker rings, and the insertion and the position of lipidic group in tail region. iii) SphK/S1P signaling pathway holds therapeutic values for many diseases. To find the exact function of each isoform of SphKs increasing the number of SphK inhibitor clinical trials is necessary.

Cockroach (CR) allergies caused by the American cockroach hyave been recognized to be repsonsible for IgE-mediated type I hypersensitivity worldwide. Per a 10 is one of the recognized main allergens of the American CR. In a previous study, we examined another American CR allergen, Per a 9 in patients with CR allergies and examined epitope sequences in this allergen. In the present study, we aimed to examine epitope sequences in the Per a 10 allergen. for this purpose, the Per a 10 gene was cloned and expressed in Escherichia coli (E. coli) systems. Our results revealed that 9 out of 16 (56.3%) sera from patients with American CR allergies reacted to Per a10, as assessed by ELISA, confirming that Per a 10 is a major allergen of the American CR. Our results also revealed that the expression of CD63 and CCR3 on passively sensitized basophils (obtained sera of patients with American CR allergies) was increased by approximately 2.3-fold, indicating that recombinant Per a 10 is functionally active. In addition, 3 immunoinformatics tools, namely the DNAStar Protean system, the Bioinformatics Predicted Antigenic Peptides (BPAP) system and the BepiPred 1.0 server were used to predict the peptides and the results revealed 8 peptides (2-12, 55-67, 98-120, 125-133, 149-160, 170-182, 201-208 and 223-227) as potential B cell epitopes of the Per a 10 allergen. Moreover, Per a 10 was predicted to have 3 T cell epitope sequences, namely 83-92, 139-147 and 162-170. The findings of our study on the CR allergen may prove to be useful in the development of peptide-based vaccine for the prevention and/or treatment of CR allergies.

Hospital-acquired infection (HAI) or nosocomial infection is an issue that frequent hospital environment. We believe conventional regulated Petri dish method is insufficient to evaluate HAI. To address this problem, metagenomic sequencing was applied to screen airborne microbes in four rooms of Beijing Hospital. With air-in amount of sampler being setup to one person's respiration quantity, metagenomic sequencing identified huge numbers of species in the rooms which had already qualified widely accepted petridish exposing standard, imposing urgency for new technology. Meanwhile,the comparative culture only got small portion of recovered species and remain blind for even cultivable pathogens reminded us the limitations of old technologies. To the best of our knowledge, the method demonstrated in this study could be broadly applied in hospital indoor environment for various monitoring activities as well as HAI study. It is also potential as a transmissible pathogen real-time modelling system worldwide.