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Objective: To explore the relationship between Polymorphism of FEN1 Gene and DNA Damage of Cytb Gene in Arsenic-Exposed Workers. Methods: The content of arsenide in urine of 79 arsenic-exposed workers and 24 agricultural workers was detected by an atomic absorption spectrophotometer. The DNA damage level of Cytb gene and the polymorphism of FEN1 gene in peripheral blood were detected by polymerase chain reaction. Results: The increased exposure to arsenic caused DNA damage of Cytb gene, resulting in an increase in the content of arsenide in urine and hypomethylation of arsenic metabolism. Meanwhile, there was a potential positive correlation between the FEN1 rs174538 AA or GA+AA allele and the DNA damage level of Cytb gene. Conclusions: The DNA damage of Cytb gene caused by arsenic exposure is related to FEN1 gene polymorphism, the content of arsenide in urine and the level of arsenic methylation metabolism.

Graphical abstract, Objectives To investigate the association between risk of VTE with 30-day mortality in COVID-19 patients. Methods 1030 COVID-19 patients were retrospective collected, with baseline data on demographics, Sequential Organ Failure Assessment (SOFA) score, and VTE risk assessment models (RAMs) including Padua Prediction Score (PPS), International Medical Prevention Registry (IMPROVE) and Caprini RAM. Results Thirty-day mortality increased progressively from 2% in patients at low risk of VTE to 63% in those at high risk defined by PPS. Similar findings were also observed by IMPROVE and Caprini score. Progressive increases in VTE risk also were associated with higher SOFA score. The presence of high risk of VTE was independently associated with mortality regardless of adjusted gender, smoking status and some comorbidities with hazard ratios of 29.19, 37.37, 20.60 for PPS, IMPROVE and Caprini RAM, respectively (P

An ongoing outbreak of 2019-nCoV pneumonia was first identified in Wuhan, Hubei province, China at the end of 2019. With the spread of the new coronavirus accelerating, person-to-person transmission in family homes or hospitals, and intercity spread of 2019-nCoV occurred. At least 40,261 cases confirmed, 23,589 cases suspected, 909 cases death and 3444 cases cured in China and worldwide 24 countries confirmed 383 cases being diagnosed, 1 case death in February 10th, 2020. At present, the mortality of 2019-nCoV in China is 2.3%, compared with 9.6% of SARS and 34.4% of MERS reported by WHO. It seems the new virus is not as fatal as many people thought. Chinese authorities improved surveillance network, made the laboratory be able to recognize the outbreak within a few weeks and announced the virus genome that provide efficient epidemiological control. More comprehensive information is required to understand 2019-nCoV feature, the epidemiology of origin and spreading, and the clinical phenomina. According to the current status, blocking transmission, isolation, protection, and alternative medication are the urgent management strategies against 2019-nCoV.

The Internet of Things (IoT) includes three core procedures: full spectrum perception, reliable transmission, and intelligent processing. It can be applied for the prevention and control of SARI (severe acute respiratory infection). By combining sensors, information technology, artificial intelligence, and available dynamic networking devices, IoT could realize long-distance communication between hospitals, patients, and medical devices, which could ultimately improve current medical conditions.

Background: Recent studies have demonstrated that airway basal stem cells (BCs) transplantation can ameliorate bleomycin-induced idiopathic pulmonary fibrosis (IPF) through lung regeneration promotion. However, BCs under oxidative stress in the alveolar microenvironment are poor in survival, causing unsatisfied efficacy of BCs transplantation. In this study, we investigated whether Coenzyme Q10(CoQ10) counteracts oxidative stress in the alveolar microenvironment, thus improved the efficacy of BCs transplantation for IPF treatment.Methods: The protective effects of CoQ10 on H2O2-induced BCs apoptosis and cytoplasmic reactive oxygen species (ROS) level were tested by flow cytometry in vitro. The therapeutic effects of BCs combined with CoQ10 were compared to a single BCs transplantation protocol in IPF treatment after two weeks and were evaluated by parameters including changes of body weight and survival rate, as well as various levels of pulmonary inflammation, α-SMA expression and hydroxyproline (HYP) in IPF mice lung tissues.Results: CoQ 10 preincubation with BCs (10 mM, 24 h) significantly reduced the late apoptosis of BCs and the number of oxidative stressful BCs as a result of H2O2 stimulation (1mM, 6h) in vitro. IPF mice models were constructed through bleomycin (5 mg/Kg) intratracheal instillation. Bleomycin-induced IPF mice showed weight loss continuously and mortality increased progressively during modeling. Serious pulmonary inflammatory cell infiltration, collagen fiber proliferation, and collagen protein deposition were observed in lung tissues of IPF mice. Though BCs transplantation alone improved indicators above in bleomycin-induced IPF mice to some extent, the combination with CoQ10 improved the transplantation efficacy and obtained better therapeutic effects.Conclusion：CoQ10 blocked H2O2-induced apoptosis of BCs and ROS production in vitro, and enhanced the efficacy of BCs transplantation on bleomycin-induced IPF in mice.

Improved therapeutic options for cervical cancer are needed. The purpose of this study was to evaluate the synergetic, inhibitory effects of ultrasound-mediated paclitaxel (PTX)- and miR-34a-loaded microbubbles (MBs) on cervical cancer. U14 cervical cancer cells and xenograft mouse tumors were treated with PTX-miR-34a-MBs. Levels of miR-34a increased in vitro and vivo after treatment with ultrasound-mediated PTX-miR-34a-MBs. Furthermore, this treatment decreased the proliferation of cervical cancer cells, microvessel density, and the expression of Bcl-2 and CDK6, both in vitro and in vivo. Furthermore, Bax expression was increased in the in vivo model. And, tumor volume and weight were significantly reduced by 78.57% and 87.97%, respectively (P

This paperA total of 62 patients with gallstones and gallbladder polyps were selected from May 2019 to May 2020, who were divided into the observation group (n=31, laparoscopic cholecystectomy) and the control group (n=31, open cholecystectomy) in a 1:1 ratio. The clinical indicators, clinical efficacy, level of pain and complication rate of the two groups were recorded and compared. Results Indicators such as the operation duration (38.64±14.42min), blood loss (30.42±8.21ml), length of stay (4.71±1.82 d), first anal exhaust (21.82±6.65min), drainage volume (72.02±4.21ml), length of incision and the time for the recovery of gastrointestinal functions in the observation group were better than the control group (P

OBJECTIVETo develop and validate a prognostic model for in-hospital mortality in COVID-19 patients using routinely collected demographic and clinical characteristics.DESIGNMulticenter, retrospective cohort study.SETTINGJinyintan Hospital, Union Hospital, and Tongji Hosptial in Wuhan, China.PARTICIPANTSA pooled derivation cohort of 1008 COVID-19 patients from Jinyintan Hospital, Union Hospital in Wuhan and an external validation cohort of 1031 patients from Tongji Hospital in Wuhan, China.MAIN OUTCOME MEASURESOutcome of interest was in-hospital mortality, treating discharged alive from hospital as the competing event. Fine-Gray models, using backward elimination for inclusion of predictor variables and allowing non-linear effects of continuous variables, were used to derive a prognostic model for predicting in-hospital mortality among COVID-19 patients. Internal validation was implemented to check model overfitting using bootstrap approach. External validation to a separate hospital was implemented to evaluate the generalizability of the model.RESULTSThe derivation cohort was a case-mix of mild-to-severe hospitalized COVID-19 patients (n=1008, 43.6% females, median age 55). The final model (PLANS), including five predictor variables of platelet count, lymphocyte count, age, neutrophil count, and sex, had an excellent predictive performance (optimism-adjusted C-index: 0.85, 95% CI: 0.83 to 0.87; averaged calibration slope: 0.95, 95% CI: 0.82 to 1.08). Internal validation showed little overfitting. External validation using an independent cohort (n=1031, 47.8% female, median age 63) demonstrated excellent predictive performance (C-index: 0.87, 95% CI: 0.85 to 0.89; calibration slope: 1.02, 95% CI: 0.92 to 1.12). The averaged predicted survival curves were close to the observed survival curves across patients with different risk profiles.CONCLUSIONSThe PLANS model based on the five routinely collected demographic and clinical characteristics (platelet count, lymphocyte count, age, neutrophil count, and sex) showed excellent discriminative and calibration accuracy in predicting in-hospital mortality in COVID-19 patients. This prognostic model would assist clinicians in better triaging patients and allocating healthcare resources to reduce COVID-19 fatality.

Background: Hospitalized patients with COVID-19 appeared high risk of venous thromboembolism (VTE), which exhibited the predictor of mortality in non-COVID-19 patients. Objectives: We aimed to investigate the association between risk of VTE with 30-day mortality in COVID-19 patients.Methods: In this retrospective cohort study, 1030 consecutive hospitalized patients with COVID-19 were recruited in two hospitals of Wuhan, China. We collected baseline data on demographics, SOFA parameters, and VTE risk assessment models (RAMs) including Padua Prediction Score (PPS), IMPROVE and Caprini RAM. The primary outcome of the study was 30-day mortality. Results: Thirty-day mortality increased progressively from 2% in patients at low risk of VTE to 63% in those at high risk defined by PPS. Similar findings were also observed for risk of VTE defined by IMPROVE and Caprini score. Progressive increases in VTE risk also were associated with higher SOFA score. Our findings showed that the presence of high risk of VTE was independently associated with 30-day mortality regardless of adjusted gender, smoking status and some comorbidities with hazard ratios of 29.19, 37.37, 20.60 for PPS, IMPROVE and Caprini RAM, respectively (P< 0.001 for all comparisons). Predictive accuracy of PPS (AUC, 0.900), IMPROVE (AUC, 0.917) or Caprini RAM (AUC, 0.861) as the risk of 30-day mortality was markedly well.Conclusions: The presence of high risk of VTE identifies a group of patients with COVID-19 at higher risk for 30-day mortality. Furthermore, there is higher accuracy of VTE RAMs to predict 30-day mortality in these patients.

Background The impact of corticosteroid therapy on outcomes of patients with coronavirus disease 2019 (COVID-19) is highly controversial. We aimed to compare the risk of death between COVID-19-related ARDS patients with corticosteroid treatment and those without. Methods In this single-center retrospective observational study, patients with ARDS caused by COVID-19 between January 20, 2020, and February 24, 2020, were enrolled. The primary outcome was 60-day in-hospital death. The exposure was prescribed systemic corticosteroids or not. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for 60-day in-hospital mortality. Results A total of 382 patients [60.7 ± 14.1 years old (mean ± SD), 61.3% males] were analyzed. The median of sequential organ failure assessment (SOFA) score was 2.0 (IQR 2.0–3.0). Of these cases, 94 (24.6%) patients had invasive mechanical ventilation. The number of patients received systemic corticosteroids was 226 (59.2%), and 156 (40.8%) received standard treatment. The maximum dose of corticosteroids was 80.0 (IQR 40.0–80.0) mg equivalent methylprednisolone per day, and duration of corticosteroid treatment was 7.0 (4.0–12.0) days in total. In Cox regression analysis using corticosteroid treatment as a time-varying variable, corticosteroid treatment was associated with a significant reduction in risk of in-hospital death within 60 days after adjusting for age, sex, SOFA score at hospital admission, propensity score of corticosteroid treatment, comorbidities, antiviral treatment, and respiratory supports (HR 0.42; 95% CI 0.21, 0.85; p = 0.0160). Corticosteroids were not associated with delayed viral RNA clearance in our cohort. Conclusion In this clinical practice setting, low-dose corticosteroid treatment was associated with reduced risk of in-hospital death within 60 days in COVID-19 patients who developed ARDS.

This study explored the synergistic effect of anti-PD-L1 antibody cationic microbubbles (MBs) for delivery of the miR-34a gene combined with ultrasound in inhibiting the cervical cancer. H&E stain, TUNEL, immunohistochemistry and RT-PCR were used to detect the change of apoptosis regulatory factors, and immunofluorescence, Flow cytometry and LDH assays were applied to evaluate the changing of immunomodulatory. In this experiment the PD-L1 Ab/miR-34a-MBs were prepared successfully. The cell targeting assay showed that U14 cells were surrounded by the PD-L1 Ab/miR-34a-MBs and microbubbles had well contrast imaging capability in vivo. With the irradiation power was 1 W/cm(2) and the irradiation time was 25 s, the gene transfection efficiency was the highest using EGFP plasmid lorded microbubbles. In vivo anti-tumor assays, the PD-L1 Ab/miR-34a-MBs showed a great potential in inhibiting tumor growth with a TGI of >50%. PD-L1 Ab/miR-34a-MBs treatment enhanced the anti-tumor effect compared with that induced by PD-L1 Ab or miR-34a alone. Firstly, PD-L1 Ab/miR-34a-MBs could gather miR-34a with high-concentration aggregation and releasing around the cervical cancer, which takes a significant role in promoting apoptosis by downregulated Bcl-2 and upregulated Bax. Furthermore, combination therapy was found to augment the activation of T lymphocytes proliferation and increase CD8+ T cells infiltration, to enhance antitumor immune killing effect. The anti-PD-L1 antibody microbubbles for delivery miR-34a gene with ultrasound were considered to be a promising combination therapy regimen via initiating apoptotic mechanism of the tumor and anti-tumor immune regulation.

Background The impact of corticosteroid therapy on outcomes of patients with Coronavirus disease-2019 (COVID-19) is highly controversial. We aimed to compare the risk of death between COVID-19-related ARDS patients with corticosteroid treatment and those without. Methods In this single-centre retrospective observational study, patients with ARDS caused by COVID-19 between 24 December 2019 and 24 February 2020 were enrolled. The primary outcome was 60-day in-hospital death. The exposure was prescribed systemic corticosteroids or not. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for 60-day in-hospital mortality. Results A total of 382 patients including 226 (59.2%) patients who received systemic corticosteroids and 156 (40.8%) patients with standard treatment were analyzed. The maximum dose of corticosteroids was 80.0 (IQR 40.0–80.0) mg equivalent methylprednisolone per day, and duration of corticosteroid treatment was 7.0 (4.0–12.0) days in total. In Cox regression analysis using corticosteroid treatment as a time-varying variable, corticosteroid treatment was associated with a significant reduction in risk of in-hospital death within 60 days (HR, 0.48; 95% CI, 0.25, 0.93; p = 0.0285). The association remained significantly after adjusting for age, sex, Sequential Organ Failure Assessment score at hospital admission, propensity score of corticosteroid treatment, and comorbidities (HR: 0.51; CI: 0.27, 0.99; p = 0.0471). Corticosteroids were not associated with delayed viral RNA clearance in our cohort. Conclusion In this clinical practice setting, low-to-moderate dose corticosteroid treatment was associated with reduced risk of death in COVID-19 patients who developed ARDS.

Few data are available on the incidence of deep vein thrombosis (DVT) in critically ill COVID-19 with thrombosis prophylaxis. This study retrospectively included 88 patients in the ICU with critically ill COVID-19 at Jinyintan Hospital in Wuhan, China. All patients underwent compression ultrasonography for identifying DVT. Firth logistic regression was used to examine the association of DVT with sex, age, hypoalbuminemia, D-dimer, and SOFA score. The median (interquartile range [IQR]) age and SOFA score of 88 patients were 63 (55–71) years old and 5 (4–6), respectively. Despite all patients receiving guideline-recommended low-molecular-weight heparin (LMWH) thromboprophylaxis, the incidence of DVT was 46% (95% CI 35–56%). Proximal DVT was recognized in 9% (95% CI 3–15%) of the patients, while 46% (95% CI 35–56%) of patients had distal DVT. All of the proximal DVT combined with distal DVT. Risk factors of DVT extension occurred in all distal DVT patients. As Padua score ≥ 4 or IMPROVE score ≥ 2, 53% and 46% of patients had DVT, respectively. Mortality was higher in patients with acute DVT (30%) compared with non-DVT (17%), but did not reach statistical significance. Hypoalbuminemia (odds ratio [OR], 0.17; 95% CI 0.06–0.05, P = 0.001), higher SOFA score (OR per IQR, 2.07; 95% CI 1.38–3.39, P = 0.001), and elevated D-dimer (OR per IQR, 1.04; 95% CI 1.03–1.84, P = 0.029) were significant DVT risk factors in multivariable analyses. High incidence of DVT was identified in patients with critically ill COVID-19, despite the use of guideline-recommended pharmacologic thromboprophylaxis. The presence of hypoalbuminemia, higher SOFA score, and elevated D-dimer were significantly independent risk factors of DVT. More effective VTE prevention and management strategies may need to be addressed.

Importance Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated. Objective To describe the clinical characteristics and outcomes in patients with COVID-19 pneumonia who developed acute respiratory distress syndrome (ARDS) or died. Design, Setting, and Participants Retrospective cohort study of 201 patients with confirmed COVID-19 pneumonia admitted to Wuhan Jinyintan Hospital in China between December 25, 2019, and January 26, 2020. The final date of follow-up was February 13, 2020. Exposures Confirmed COVID-19 pneumonia. Main Outcomes and Measures The development of ARDS and death. Epidemiological, demographic, clinical, laboratory, management, treatment, and outcome data were also collected and analyzed. Results Of 201 patients, the median age was 51 years (interquartile range, 43-60 years), and 128 (63.7%) patients were men. Eighty-four patients (41.8%) developed ARDS, and of those 84 patients, 44 (52.4%) died. In those who developed ARDS, compared with those who did not, more patients presented with dyspnea (50 of 84 [59.5%] patients and 30 of 117 [25.6%] patients, respectively [difference, 33.9%; 95% CI, 19.7%-48.1%]) and had comorbidities such as hypertension (23 of 84 [27.4%] patients and 16 of 117 [13.7%] patients, respectively [difference, 13.7%; 95% CI, 1.3%-26.1%]) and diabetes (16 of 84 [19.0%] patients and 6 of 117 [5.1%] patients, respectively [difference, 13.9%; 95% CI, 3.6%-24.2%]). In bivariate Cox regression analysis, risk factors associated with the development of ARDS and progression from ARDS to death included older age (hazard ratio [HR], 3.26; 95% CI 2.08-5.11; and HR, 6.17; 95% CI, 3.26-11.67, respectively), neutrophilia (HR, 1.14; 95% CI, 1.09-1.19; and HR, 1.08; 95% CI, 1.01-1.17, respectively), and organ and coagulation dysfunction (eg, higher lactate dehydrogenase [HR, 1.61; 95% CI, 1.44-1.79; and HR, 1.30; 95% CI, 1.11-1.52, respectively] and D-dimer [HR, 1.03; 95% CI, 1.01-1.04; and HR, 1.02; 95% CI, 1.01-1.04, respectively]). High fever (≥39 °C) was associated with higher likelihood of ARDS development (HR, 1.77; 95% CI, 1.11-2.84) and lower likelihood of death (HR, 0.41; 95% CI, 0.21-0.82). Among patients with ARDS, treatment with methylprednisolone decreased the risk of death (HR, 0.38; 95% CI, 0.20-0.72). Conclusions and Relevance Older age was associated with greater risk of development of ARDS and death likely owing to less rigorous immune response. Although high fever was associated with the development of ARDS, it was also associated with better outcomes among patients with ARDS. Moreover, treatment with methylprednisolone may be beneficial for patients who develop ARDS.

ImportanceHeart injury can be easily induced by viral infection such as adenovirus and enterovirus. However, whether coronavirus disease 2019 (COVID-19) causes heart injury and hereby impacts mortality has not yet been fully evaluated.ObjectiveTo explore whether heart injury occurs in COVID-19 on admission and hereby aggravates mortality later.Design, Setting, and ParticipantsA single-center retrospective cohort study including 188 COVID-19 patients admitted from December 25, 2019 to January 27, 2020 in Wuhan Jinyintan Hospital, China; follow up was completed on February 11, 2020.ExposuresHigh levels of heart injury indicators on admission (hs-TNI; CK; CK-MB; LDH; α-HBDH).Main Outcomes and MeasuresMortality in hospital and days from admission to mortality (survival days).ResultsOf 188 patients with COVID-19, the mean age was 51.9 years (standard deviation: 14.26; range: 21∼83 years) and 119 (63.3%) were male. Increased hs-TnI levels on admission tended to occur in older patients and patients with comorbidity (especially hypertension). High hs-TnI on admission (≥ 6.126 pg/mL), even within the clinical normal range (0∼28 pg/mL), already can be associated with higher mortality. High hs-TnI was associated with increased inflammatory levels (neutrophils, IL-6, CRP, and PCT) and decreased immune levels (lymphocytes, monocytes, and CD4+ and CD8+ T cells). CK was not associated with mortality. Increased CK-MB levels tended to occur in male patients and patients with current smoking. High CK-MB on admission was associated with higher mortality. High CK-MB was associated with increased inflammatory levels and decreased lymphocytes. Increased LDH and α-HBDH levels tended to occur in older patients and patients with hypertension. Both high LDH and α-HBDH on admission were associated with higher mortality. Both high LDH and α-HBDH were associated with increased inflammatory levels and decreased immune levels. hs-TNI level on admission was negatively correlated with survival days (r= -0.42, 95% CI= -0.64∼-0.12, P=0.005). LDH level on admission was negatively correlated with survival days (r= -0.35, 95% CI= -0.59∼-0.05, P=0.022).Conclusions and RelevanceHeart injury signs arise in COVID-19, especially in older patients, patients with hypertension and male patients with current smoking. COVID-19 virus might attack heart via inducing inflammatory storm. High levels of heart injury indicators on admission are associated with higher mortality and shorter survival days. COVID-19 patients with signs of heart injury on admission must be early identified and carefully managed by cardiologists, because COVID-19 is never just confined to respiratory injury.Key pointsQuestionDoes coronavirus disease 2019 (COVID-19) cause heart injury and hereby impact mortality?FindingsIn this retrospective cohort study including 188 patients with COVID-19, patients with high levels of high-sensitivity cardiac troponin I (hs-TNI) on admission had significantly higher mortality (50.0%) than patients with moderate or low levels of hs-TNI (10.0% or 9.1%). hs-TNI level on admission was significantly negatively correlated with survival days (r= -0.42, 95% CI= -0.64∼-0.12, P=0.005).MeaningCOVID-19 patients with signs of heart injury on admission must be early identified and carefully managed by cardiologists, in order to maximally prevent or rescue heart injury-related mortality in COVID-19.

Additional file 1: . Appendix Text 1. Implementation and estimates of Fine-Gray model. Appendix Text 2. Internal validation by bootstrap. Appendix Text 3. Two updated models. Figure 1. Cumulative mortality for derivation and validation cohort. Figure 2. The Schoenfeld residual plots for each predictor, test of proportional hazards. Table 1. “Baseline”* mortality (Wuhan, China). Table 2. Thresholds and corresponding proportion and death toll included in each risk group. Table 3. Basic characteristics used in entropy balancing in Derivation cohort, New York cohort and Lombardy cohort. Table 4. “Baseline”* mortality (New York, USA). Table 5. “Baseline”* mortality (Lombardy, Italy). Table 6 Methodology quality assessment based on PROBAST risk of bias assessment tool

The aim is to diagnose COVID-19 earlier and to improve its treatment by applying medical technology, the “COVID-19 Intelligent Diagnosis and Treatment Assistant Program (nCapp)” based on the Internet of Things. Terminal eight functions can be implemented in real-time online communication with the “cloud” through the page selection key. According to existing data, questionnaires, and check results, the diagnosis is automatically generated as confirmed, suspected, or suspicious of 2019 novel coronavirus (2019-nCoV) infection. It classifies patients into mild, moderate, severe or critical pneumonia. nCapp can also establish an online COVID-19 real-time update database, and it updates the model of diagnosis in real time based on the latest real-world case data to improve diagnostic accuracy. Additionally, nCapp can guide treatment. Front-line physicians, experts, and managers are linked to perform consultation and prevention. nCapp also contributes to the long-term follow-up of patients with COVID-19. The ultimate goal is to enable different levels of COVID-19 diagnosis and treatment among different doctors from different hospitals to upgrade to the national and international through the intelligent assistance of the nCapp system. In this way, we can block disease transmission, avoid physician infection, and epidemic prevention and control as soon as possible.

Additional file 1: eMethods, eTable 1 and 2, and eFigure 1 were included.

Background: Inpatients with coronavirus disease 2019 (COVID-19) have been well depicted in clinical characteristics. However, few studies reported post-discharge conditions, especially mental health status, for survivors following COVID-19. In this study, we aimed to first report mental health status in COVID-19 survivors and explore relevant influence factors. Methods: In this descriptive case series, we enrolled a population of 370 COVID-19 survivors in Wuhan Jinyintan Hospital, China. Survivors were discharged during Jan 4 and Feb 12, 2020. Telephone follow-up was conducted. Readmission status and post-discharge symptoms and signs were inquired. Mental health conditions of anxiety and depression were assessed using The Generalized Anxiety Disorder Screener (GAD-7) and Patient Health Questionnaire-9 (PHQ-9), respectively. Results: The median post-discharge follow-up period was 22 days (interquartile range 20~30 days). Of the 370 COVID-19 survivors, no survivors were readmitted due to recurrence of SARS-CoV-2-positive pneumonia. Sixty (16.2%) survivors had post-discharge cough and 45 (12.2%) had breathlessness after activity. One hundred and seventy-three (46.8%) survivors worried about recurrence and 174 (47.0%) worried about infection to others such as their family. Two hundred and ninety-three (79.2%) survivors took a home quarantine lifestyle. Fifty (13.5%) survivors occurred anxiety and 40 (10.8%) survivors occurred depression. Survivors were most bothered by sleeping disorders (29.5%). Four survivors (1.1%) once had thoughts of suicide in several days. Three hundred and fifty-six (96.2%) survivors were willing to return to hospital for health examination. Anxiety was significantly associated with post-discharge respiratory symptoms, worry about recurrence and worry about infection to others (P

Additional file 2: TRIPOD Checklist: Prediction Model Development

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with high morbidity and mortality. Mesenchymal stem cells (MSCs) have been shown to improve ALI, and the imbalance of regulatory T cells (Tregs) and Th17 cells is associated with mortality in ALI/ARDS patients. However, whether administration of lung-resident MSC (LRMSC) improves lung injury and regulates the balance of Tregs and Th17 cells remains unknown. An ALI animal model was induced by LPS, and PBS or LRMSC were administered via tail vein after 4 h. LRMSC were subsequently detected in the lungs by a live imaging system (Berthold LB983, Germany). Lung morphology; lung wet-to-dry weight ratio; and total protein concentration, inflammatory cells, and cytokines in bronchoalveolar lavage fluid (BALF) and plasma were determined. The percentage of Tregs in lung and spleen, and of Th17 cells in lung and blood, were also evaluated. The results showed that LRMSC not only attenuated histopathological damage but also mediated the downregulation of lung wet-to-dry weight ratio and the reduction of total protein concentration and inflammatory cells in BALF. LRMSC also decreased inflammatory cytokines in both BALF and plasma and increased KGF-2 and surfactant protein C (SPC) expression in the lung. Flow cytometry revealed the upregulation of Tregs and the downregulation of Th17 cells, and the increase in the ratio of Tregs and Th17 cells. The live imaging system showed that LRMSC migrated to and were retained in the injured area. In conclusion, the results indicated that administration of LRMSC attenuates LPS-induced ALI via upregulating the balance of Tregs and Th17 cells.

Monocytic myeloid-derived suppressor cells (M-MDSCs), granulocytic MDSC (G-MDSCs) and regulatory T cells (Tregs) inhibit adaptive anti-tumor immunity and undermine the efficacy of anti-PD-1 therapy. However, the impact of anti-PD-1 treatment on these immunosuppressive cells has not been clearly defined in non-small cell lung cancer (NSCLC). In this retrospective study, 27 advanced NSCLC patients were divided into partial response (PR), stable disease (SD), and progressive disease (PD) groups. The impact of anti-PD-1 therapy on circulating Tregs, G-MDSCs, and M-MDSCs was assessed by flow cytometer. Here, we found that anti-PD-1 treatment boosted circulating Tregs levels, which presented the most remarkable augment during the first two therapeutic cycles, in NSCLC patients. In contrast, anti-PD-1 therapy did not overall change G-MDSCs and M-MDSCs levels. However, the PR group had a higher baseline level of M-MDSCs, which exhibited a significant decrease after the first cycle of anti-PD-1 treatment. Besides, M-MDSCs levels in the PR group were maintained at a low level in the following therapeutic cycles. Consistently, Tregs levels robustly increased in the syngeneic tumor model after anti-mouse PD-1 Ab treatment. Accordingly, M-MDSCs neutralization by anti-mouse ly6c Ab enhanced the anti-tumor efficacy of anti-PD-1 therapy in mice. Finally, the decreased M-MDSCs levels were associated with the enhanced effector CD8+ T cells expansion in the PR group and mice. In conclusion, anti-PD-1 therapy upregulates Tregs levels in NSCLC patients, and the M-MDSC levels are associated with the anti-tumor efficacy of anti-PD-1 treatment. Neutralization of M-MDSCs may be a promising option to augment anti-PD-1 therapy efficacy in NSCLC., Highlights • Anti-PD-1 therapy upregulates Tregs levels in NSCLC patients and mouse model. • M-MDSCs exhibit a significant decrease in the PR group after anti-PD-1 therapy. • M-MDSCs neutralization augments anti-PD-1 efficacy in mouse model. • The increased effector CD8+ T cells are associated with the better anti-PD-1 efficacy in the PR group and mouse model.

Aims Anti-PD-L1 monoclonal antibody (mAb)-conjugated ultrasound (US) lipid-shelled microbubbles (PD-L1-MBs) were successfully synthesized to investigate whether that PD-L1-MBs could enhance anti-tumor effect in combination therapy with cisplatin (CDDP) under ultrasound mediation. Main methods Based on affinity between biotin and streptavidin, we prepared microbubbles conjugated with anti-PD-L1 mAb by membrane hydration and mechanical oscillation. A subcutaneous tumor model was established to test the anti-tumor effect and immunological activity of this combination therapy. Bax and Bcl-2 expression were detected by RT-qPCR and Immunohistochemistry. Cells undergoing apoptosis in tissue section were determined by TUNEL. Proliferation of splenocytes was analyzed by Flow cytometry. A cytotoxic T lymphocyte assay was performed by CTL. Expression of PD-L1 and CD8 in tissue section was examined by immunologfluorescence. Expression of IFN-γ, TNF-α, CD86 and CD80 was also detected by RT-qPCR. Key findings We observed that the growth of the subcutaneous tumor was significantly slower in combined group than that in the group treated with either drug or microbubbles. Moreover, higher antitumor activity was observed in the combined group than that in cisplatin alone, which could be reflected by the number of apoptotic cells in tumor tissues and over expression of bax in the combined group. This combination treatment also exhibited a better immunological activity, increasing the infiltration of CD8+ T cells and the expression of several revelant cytokines. Significance The ultrasound lipid-shelled PD-L1-MBs may enhance anti-tumor effects of cisplatin by blocking the PD-L1 site and improving immune function.

Highlights • Patients in the experimental group received intravenous ribavirin versus supportive care only in the control group. • Ribavirin was not associated with reduced negative conversion time of SARS-CoV-2 PCR test compared with the control group. • Ribavirin did not reduce the mortality rate compared with the control group., The aim of this study was to compare ribavirin therapy versus supportive therapy only for patients with severe coronavirus disease 2019 (COVID-19). A total of 115 patients with laboratory-confirmed COVID-19 were retrospectively analysed. All patients received supportive care as well as regular laboratory and clinical monitoring. The 115 patients comprised 44 patients who received intravenous ribavirin (treatment group) and 71 who did not (control group). Baseline laboratory and clinical characteristics were similar between the two groups. The negative conversion time for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR in the ribavirin group was 12.8 ± 4.1 days compared with 14.1 ± 3.5 days in the control group (P = 0.314). Moreover, 7/41 patients (17.1%) in the ribavirin group died compared with 17/69 (24.6%) in the control group (P = 0.475). Adverse effects were similar between the two groups. In conclusion, in patients with severe COVID-19, ribavirin therapy is not associated with improved negative conversion time for SARS-CoV-2 test and is not associated with an improved mortality rate. Further assessment in designed randomised controlled trials is recommended.

New norcantharidin-conjugated hydroxypropyltrimethyl ammonium chloride chitosan derivatives (NCTD-HACCs) were synthesized and characterized by 1H NMR, Fourier-transform infrared spectroscopy (FT-IR), and wide-angle X-ray diffraction (WAXD). Two NCTD-HACCs with different degrees of substitution (DS) (12.2% and 24.8%) were obtained, which had good water solubility. NCTD was released from the NCTD-HACCs via hydrolysis, faster in pH 5.0 than pH 7.4 and presenting one biphasic drug release pattern with rapid release at the initial stage and slow release later. Fluorescence microscope and flow cytometry analysis demonstrated that the NCTD-HACC was endocytosized into MGC80-3 cells and the uptaken amount increased as incubation time. Compared with free NCTD, the NCTD-HACCs showed lower in vitro anti-tumor activity against human gastric cancer MGC80-3 cells, but higher in vivo tumor growth inhibition in S180 tumor-bearing mice. The in vivo near-infrared (NIR) fluorescence real-time imaging result showed the fluorescence intensity in tumor was much higher than that in heart, liver, spleen and lung (except kidney) after i.v. injection of the FITC-labeled NCTD-HACC2, indicating specific accumulation of the NCTD-HACC in tumor.

Background and objective Alveolar fluid clearance (AFC) is important for the resolution of acute lung injury (ALI). The role of cystic fibrosis transmembrane conductance regulator (CFTR) in AFC has not been entirely elucidated in animal models of ALI. The aim of this study was to investigate the role of CFTR and its mechanisms in AFC in normal and ALI mice. Methods Seventy mice were randomly divided into 14 groups and ALI was established by intratracheal instillation of lipopolysaccharide (LPS). After 48 h, CFTR activator CFTRact-16 or inhibitor CFinh-172 with or without β-agonist was instillated intratracheally and AFC was measured with radioisotopic tracer. Results Although there was no effects of CFTRact-16 on AFC in mice with or without isoproterenol, CFinh-172 markedly decreased isoproterenol-stimulated AFC in both normal (P

[Purpose] The aim of this study was to assess the efficacy of noninvasive ventilation (NIV) in acute respiratory distress syndrome (ARDS). [Subjects and Methods] The clinical data of 58 patients with ARDS that required mechanical ventilation in two intensive care units (ICU) was reviewed. [Results] Endotracheal intubation was performed in 55.17% of the total patients and in 39.53% of the patients who received NIV treatment. The APACHE II score for patients who only received IV was significantly higher than those who only underwent NIV (25.67 ± 5.30 vs. 18.12 ± 7.20). However, there were no significant differences in 28-day/90-day survival rates, duration of mechanical ventilation, and length of ICU stay between these two groups. For patients from a NIV-to-IV group, the APACHE II scores before endotracheal intubation were higher than the scores from IV patients (26.12 ± 4.08 vs. 21.94 ± 6.10). The 90-day survival rate in the NIV-to-IV group was significantly lower than that of the IV-only group (23.5% vs. 73.3%), although there was no difference in the 28-day survival rate between the two groups. [Conclusion] The application of NIV reduces the percentage of patients requiring endotracheal intubation.

A new intravascular fluorosensor was developed and validated for inline P CO 2 monitoring. The P CO 2 sensor was based on the fluorescent indicator 1-hydroxypyrene-3,6,8-trisulfonate. The P CO 2 sensor was then immersed in various solutions in vitro and carotid artery bypass of rabbits in vivo for testing. Changes of P CO 2 in solutions and blood were created by bubbling CO2/N2 and hyperventilation/hypoventilation, respectively. The changes of fluorescent intensity over P CO 2 range of 14–150 mmHg was linear. The resolution of the whole sensor system was 1 mmHg, with a bias ± SD of −0.1 ± 2.9 mmHg and precision ± SD of 2.1 ± 1.9 mmHg. The sensor signal has been stable during measurement for at least 25 h and was insensitive to fluctuations of ions concentration and osmosis at pathophysiological limits. The performance of the sensor is in agreement with blood gas analyzer in a wide range of P CO 2 and it is qualified for continuous intravascular measurement of blood P CO 2 at various conditions.

Continuous intra-arterial blood pH monitoring is highly desirable in clinical practice. However, devices with appreciable accuracy are still not commercially available to date. In this study, we present a fiber-optic fluorosensor that can be used to continuously and accurately measure blood pH changes. The pH sensor is developed based on a proton-sensitive fluorescence dye, N-allyl-4-(4'-methyl-piperazinyl)-1,8-naphthalimide, which is bonded covalently to an optical fiber through heat polymerization. Fluorescence intensity was recorded after the sensor was exposed to different pH buffer solutions or intra-arterial blood in rabbits. Fluorescence intensity with emission peak at 510 nm decreased immediately as the blood pH increased. Linear and reproducible responses were observed when pH ranges from 6.8 to 8.0 with res olution of 0.03 pH units. The correlation coefficient between the pH sensor and the conventional blood gas analyzer was 0.93 in vivo (n = 75, p

BACKGROUND AND OBJECTIVE Continuous monitoring of PaO(2) in seriously ill patients is an important aspect of clinical management, especially for patients with acute lung injury (ALI) or acute respiratory distress syndrome. We have developed a fibreoptic sensor to detect PaO(2)in vivo based on fluorescence quenching technology. In this study we evaluated the sensitivity of this sensor in monitoring PaO(2) in a rabbit model with ALI. METHODS The oxygen sensor is a membrane made of Ru(dpp)(3)(PF6)(2), poly-2-methacryloyloxyethyl phosphorylcholine and butylmethacylate copolymer p-(MPC-co-BMA) located at the tip of the optical fibre. The sensor was inserted into the carotid artery of the animals and monitored PaO(2) continuously. Oleic acid was intravenously injected to induce lung injury. Simultaneous comparisons were made between PaO(2) measured by blood gas analysis and PaO(2) measured by the fibreoptic sensor, both before and after lung injury. RESULTS The fluorescence intensity decreased gradually following ALI, reflecting increasing hypoxia. Correlation coefficients between measurements by the oxygen sensor and by the blood gas analysis were 0.995 +/- 0.003, 0.994 +/- 0.002 and 0.993 +/- 0.005 (P < 0.05) for control animals, animals with ALI and animals with electrolyte disturbance, respectively. The bias and precision for normal animals was -1.5 +/- 10.8 mm Hg, for animals with ALI was -1.2 +/- 11.2 mm Hg and for animals with electrolyte disturbance was -1.4 +/- 9.2 mm Hg. CONCLUSIONS The oxygen sensor showed high accuracy and stability for continuous monitoring of PaO(2) in normal animals, in animals with ALI and in animals with electrolyte disturbance, suggesting that it may be clinically useful in the continuous measurement of oxygen partial pressure.