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Mycoplasma penumoniae (MP) is a common etiological agent of community-acquired pneumonia. However, there has been an increasing incidence of macrolide-unresponsive Mycoplasma penumoniae pneumonia (MUMPP) in recent years. The treatment of MUMPP requires further investigation. In this report, we describe a case of MUMPP complicated by secondary spontaneous pneumothorax. The patient was unresponsive to initial macrolide treatment and his pneumonia worsened with increasing hypoxemic respiratory failure. However, after receiving a novel tetracycline and a carbapenem antibiotic as anti-infective agents, glucocorticoid for anti-inflammatory and bronchoscopic interventions to clear the bronchial casts, his fever and hypoxia resolved, and his lung lesions had significantly improved. Symptomatic supportive measures, including supplemental oxygen, was provided for the management of spontaneous pneumothorax developed twenty days after discharge. At follow-up, he did not experience any more initial symptoms. All indexes remained normal for half a year. This study represents the initial investigation into the utilization of tigecycline in conjunction with bronchoscopic interventions including bronchoalveolar lavage (BAL) and bronchoscopic cryotherapy (BC) in the treatment of MUMPP, glucocorticoid can be considered for anti-inflammatory purposes, especially for patients with severe pneumonia. The findings from this case offer valuable insights into a potential therapeutic approach for individuals afflicted with MUMPP.

Background: The present study aimed to investigate the relationship between swollen limb circumference and compartment pressure after a snakebite and to evaluate the diagnostic value of the circumference difference between the healthy and affected sides and the circumference growth rate for snake venom-induced compartment syndrome (CS). Method: The study was based on a prospective cohort study of snakebite patients at the emergency department of West China Hospital from May 2021 to October 2022. The snakebite patients were divided into the CS and non-compartment syndrome (NCS) groups. The diagnostic value of the circumference of the swollen limb for the CS after snakebite was evaluated using a receiver-operating characteristic curve analysis, and the cut-off value of the circumference of the swollen limb for CS after snakebite was calculated with sensitivity and specificity. Result: The present study enrolled 115 patients with severely swollen limbs after snakebite. The mean age was 59.1 ± 13.6 years, with 58 (50.4 %) female cases and 57 (49.6 %) male cases. There were 33 (28.7 %) cases where the upper limbs were injured and 82 (71.3 %) cases where the lower limbs were injured. These patients were divided into CS (n = 19) and NCS (n = 96) groups. The area under the curve (AUC) for the 15 cm circumference difference and circumferential growth rate of the upper edge of the patella was 0.683 (95 % CI 0.508 to 0.858, P = 0.037), and 0.685 (95 % CI 0.512 to 0.858, P = 0.035). The optimal cut-off values for the 15 cm circumference difference and circumferential growth rate of the upper edge of the patella to distinguish CS and NCS were 2.8 cm (sensitivity = 76.9 %, specificity = 66.7 %) and 7 % (sensitivity = 76.9 %, specificity = 66.7 %), respectively. Conclusion: Limb circumference measurement is a non-invasive, convenient, effective, and repeatable bedside test that can assist clinicians in the early detection of suspected snake venom-induced CS in patients exhibiting limb swelling after snake bites.

This study aimed to create a robust prediction model for sepsis patient mortality and identify key biomarkers in those with myocardial injury. A retrospective analysis of 261 sepsis inpatients was conducted, with 44 deaths and 217 recoveries. Key factors were assessed via univariate and multivariate analyses, revealing myocardial injury, shock, and pulmonary infection as independent mortality risk factors. Using LASSO regression, a reliable prediction model was developed and internally validated. Additionally, procalcitonin (PCT) emerged as a sensitive biomarker for myocardial injury prediction in sepsis patients. In summary, this study highlights myocardial injury, shock, and pulmonary infection as independent risk factors for sepsis-related deaths. The LASSO-based prediction model effectively forecasts the prognosis of septic patients with myocardial injury, with PCT showing promise as a predictive biomarker.

Abstract Since its discovery in 2019, coronavirus disease 2019 (COVID-2019) spans a wide clinical spectrum from the asymptomatic stage, mild infection, to severe pneumonia. In patients with COVID-2019, factors such as advanced age, diabetes, or hypertension are associated with a significantly increased risk of severe diseases and death. Of note, the mechanisms underlying differences in the risk and symptoms of COVID-2019 among different populations are still poorly characterized. Accordingly, it is imperative to elucidate potential pathophysiological mechanisms and develop targeted therapeutic approaches for COVID-2019 infection. N6-methyladenosine (m6A) is one of the most common modifications in mammalian RNA transcripts and is widely found in messenger RNAs and some non-coding RNAs. It has been reported that m6A methylation modifications are present in viral RNA transcripts, which are of great significance for the regulation of the viral life cycle. Furthermore, m6A methylation has recently been found to be strongly associated with COVID-2019 infection. Therefore, this article reviews recent advances in studies related to the role of m6A methylation in COVID-2019 infection.

Abstract Background Spontaneous pneumomediastinum (SPM) was defined by the appearance of free air in the mediastinum that was not preceded by trauma, surgery, or other medical procedures. Among the numerous manifestations of SPM, abdominal pain had seldom been described. Case presentation A 25-year-old man presented to the emergency department with nausea, vomiting, and abdominal pain for 7 days. The presenting clinical features and the radiological results were suggestive of psychogenic vomiting with spontaneous pneumomediastinum in a patient who suffered from abdominal pain. Conclusions The special feature of this case was the elucidation of a rare cause of abdominal pain, which should be differentiated in patients with vomiting combined with abdominal pain. The importance of this case was that its recognition may prevent unnecessary procedures to rule out or treat other causes of abdominal pain.

Abstract Nowadays, the diagnosis and treatment of COPD are often based on the results of lung function tests. Certain individuals, however, are not candidates for lung function testing due to pulmonary bullae, cardiac failure, low lung function, and other factors. Therefore, we evaluated whether serum tyrosine3-monooxygenase/tryptophan5-monooxygenase activation protein β (14-3-3β) could be a biomarker for the diagnosis of stable COPD patients. The expression of serum 14-3-3β protein was evaluated by an enzyme-linked immunosorbent assay. The association between its concentrations and clinical parameters of stable COPD patients were analyzed by correlation analysis and ROC curve. The results before propensity score matching (PSM) showed that serum 14-3-3β protein concentrations (ng/ml) in stable COPD patients were significantly higher than in healthy controls (P

Abstract Central airway obstruction caused by neck and chest tumors is a very dangerous oncological emergency with high mortality. Unfortunately, there is few literature to discuss an effective way for this life-threating condition. Providing effective airway managements, adequate ventilation and emergency surgical interventions are very important. However, traditional airway managements and respiratory support has only limited effect. In our center, using extracorporeal membrane oxygenation (ECMO) as a novel approach to manage patient with central airway obstruction caused by neck and chest tumors has been adopted. We aimed to show the feasibility: using early ECMO to manage difficult airway, provide oxygenation and support surgical procedure for patients with critical airway stenosis caused by neck and chest tumors. We designed a single-center, small sample size retrospective study based on real-world. We identified 3 patients with central airway obstruction caused by neck and chest tumors. ECMO was used to ensure adequate ventilation to emergency surgery. Control group cannot be established. Because traditional manner very likely led to death of such patients. Details of clinical characteristics, ECMO, surgery and survival outcomes were recorded. Acute dyspnea and cyanosis were the most frequent symptoms. All patients (3/3) showed descending arterial partial pressure of oxygen (PaO2). Computed tomography (CT) revealed severe central airway obstruction caused by neck and chest tumors in all cases (3/3). All patients (3/3) had definite difficult airway. All cases (3/3) received ECMO support and emergency surgical procedure. Venovenous ECMO was the common mode for all cases. 3 patients weaned off ECMO successfully without any ECMO-related complications. Mean duration of ECMO was 3 h (range: 1.5–4.5 h). Under ECMO support, difficult airway management and emergency surgical procedure were finished successfully for all cases (3/3). The mean ICU stay was 3.3 days (range: 1–7 days), and the mean general ward stay was 3.3 days (range: 2–4 days). Pathology demonstrated the tumor dignity for 3 patients including 2 malignant cases and 1 benign case. All patients (3/3) were discharged from hospital successfully. We showed that early ECMO initiation was a safe and feasible approach to manage difficult airway for patients with severe central airway obstruction caused by neck and chest tumors. Meanwhile, early ECMO initiation could ensure security for airway surgical procedure.

Bromadiolone, as a second-generation coumarin anticoagulant rodenticide, may accidently cause harm to humans and non-target animals when overused or misused due to its high toxicity and long-lasting effects. In some severe cases such as the presence of active bleeding, treatment should involve the administration of hemoperfusion therapy. Nafamostat mesylate is a synthesized protease inhibitor that inhibits most factors in the coagulation process, preventing clotting and ensuring smooth blood flow during the procedure. Nafamostat mesylate helps maintain the efficacy and safety of hemoperfusion treatment. Despite its wide application in Japan, the clinical practice and research of nafamostat mesylate are limited in China, especially for patients undergoing maintenance hemodialysis. This paper reports two cases of bromadiolone poisoning and describes the treatment procedure and therapeutic effect of anticoagulation in hemoperfusion therapy with nafamostat mesylate.

Abstract Background Pneumocystis jirovecii pneumonia (PJP) is one of the most common opportunistic infections in immunocompromised patients. However, the accurate prediction of the development of PJP in non-HIV immunocompromised patients is still unclear. Methods Non-HIV immunocompromised patients confirmed diagnosis of PJP by the clinical symptoms, chest computed tomography and etiological results of metagenomic next-generation sequencing (mNGS) were enrolled as observation group. Another group of matched non-HIV immunocompromised patients with non-PJP pneumonia were enrolled to control group. The risk factors for the development of PJP and the co-pathogens in the bronchoalveolar lavage fluid (BALF) detected by mNGS were analyzed. Results A total of 67 (33 PJP, 34 non-PJP) participants were enrolled from Fujian Provincial Hospital. The ages, males and underlying illnesses were not significantly different between the two groups. Compared to non-PJP patients, PJP patients were more tends to have the symptoms of fever and dyspnea. The LYM and ALB were significantly lower in PJP patients than in non-PJP patients. Conversely, LDH and serum BDG in PJP patients were significantly higher than in non-PJP controls. For immunological indicators, the levels of immunoglobulin A, G, M and complement C3, C4, the numbers of T, B, and NK cells, had no statistical difference between these two groups. Logistic multivariate analysis showed that concomitant use of corticosteroids and immunosuppressant (OR 14.146, P = 0.004) and the lymphocyte counts

Introduction: A large number of COVID-19 patients are in recovery, and millions of people are vaccinated for COVID-19 globally. This calls for a rapid screening strategy of SARS-CoV-2 protective antibodies, generated in rehabilitated and vaccinated populations. Methods: Serum samples collected over a follow-up period of six months from 306 COVID-19 cases discharged from Wuhan Tongji Hospital were analyzed. Anti-S Abs were detected by colloidal gold immunochromatographic assay (GICA), and neutralizing antibodies (nAbs) were detected by chemiluminescent microparticle immunoassay (CMIA). Results: Most COVID-19 survivors tested positive for anti-S Abs (83.7%) and nAbs (98.0%) 6 months after being discharged from the hospital, and the levels of anti-S Abs in the blood were highly positively correlated with nAbs (r = 0.652, P < 0.0001). The positivity rate of nAbs for patients with anti-S Abs positive was 100%. Conclusions: There is a good agreement between anti-S Abs detected by GICA and nAbs detected by CMIA. It indicates that anti-S Abs detected by GICA may be used as a cheaper screening strategy for detectable SARS-CoV-2 nAbs in COVID-19 convalescent individuals.

Abstract To describe the long-term health outcomes of patients with COVID-19 and investigate the potential risk factors. Clinical data during hospitalization and at a mean (SD) day of 249 (15) days after discharge from 40 survivors with confirmed COVID-19 (including 25 severe cases) were collected and analyzed retrospectively. At follow-up, severe cases had higher incidences of persistent symptoms, DLCO impairment, and higher abnormal CT score as compared with mild cases. CT score at follow-up was positively correlated with age, LDH level, cumulative days of oxygen treatment, total dosage of glucocorticoids used, and CT peak score during hospitalization. DLCO% at follow-up was negatively correlated with cumulative days of oxygen treatment during hospitalization. DLCO/VA% at follow-up was positively correlated with BMI, and TNF-α level. Among the three groups categorized as survivors with normal DLCO, abnormal DLCO but normal DLCO/VA, and abnormal DLCO and DLCO/VA, survivors with abnormal DLCO and DLCO/VA had the lowest serum IL-2R, IL-8, and TNF-α level, while the survivors with abnormal DLCO but normal DLCO/VA had the highest levels of inflammatory cytokines during hospitalization. Altogether, COVID-19 had a greater long-term impact on the lung physiology of severe cases. The long-term radiological abnormality maybe relate to old age and the severity of COVID-19. Either absent or excess of inflammation during COVID-19 course would lead to the impairment of pulmonary diffusion function.

BackgroundAsthma patients potentially have impaired adaptive immunity to virus infection. The levels of SARS-CoV-2-specific adaptive immunity between COVID-19 survivors with and without asthma are presently unclear.MethodsCOVID-19 survivors (patients with asthma n=11, with allergies n=8, and COVID-19 only n=17) and non-COVID-19 individuals (asthmatic patients n=10 and healthy controls n=9) were included. The COVID-19 patients were followed up at about 8 months and 16 months after discharge. The clinical characteristics, lymphocyte subsets, memory T cells, and humoral immunity including SARS-CoV-2 specific antibodies, SARS-CoV-2 pseudotyped virus neutralization assay, and memory B cells were analyzed in these subjects.ResultsThe strength of virus-specific T cell response in COVID-19 survivors was positively correlated with the percentage of blood eosinophils and Treg cells (r=0.4007, p=0.0188; and r=0.4435, p=0.0086 respectively) at 8-month follow-up. There were no statistical differences in the levels of SARS-CoV-2-specific T cell response between the COVID-19 survivors with, and without, asthma. Compared to those without asthma, the COVID-19 with asthma survivors had higher levels of SARS-CoV-2-specific neutralizing antibodies (NAbs) at the 8-month follow-up (p

Objective: To evaluate the clinical diagnostic value of positive acid-fast staining combined with negative GeneXpert MTB/RIF in the diagnosis of non-tuberculous mycobacteria pulmonary disease (NTM-PD). Methods: A total of 133 inpatients with confirmed NTM-PD were included consecutively between January 1, 2018 and December 31, 2019, at Tongji Hospital and Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, in Wuhan, China. One hundred patients with confirmed pulmonary tuberculosis (PTB) were randomly included as the control group. Results: The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of positive acid-fast staining combined with a negative GeneXpert MTB/RIF result were 51.13% (95% confidence interval (CI) 42.52–59.73%), 97.00% (95% CI 93.60–100.40%), 95.78% (95% CI 90.98–100.57%), and 59.88% (95% CI 52.25–67.51%), respectively. When subjects were limited to patients with positive acid-fast staining, the sensitivity of a negative GeneXpert MTB/RIF result was 88.31% (95% CI 80.97–95.65%). When acid-fast staining was conducted ≥3 times, the sensitivity of this combination diagnosis method increased to 61.67% (95% CI 49.00–74.33%). Conclusions: Positive acid-fast staining combined with a negative GeneXpert MTB/RIF result could be an effective and time-saving method for the diagnosis of NTM-PD.

Background: Regulation or restoration of therapeutic sensitivity to glucocorticoids is important in patients with steroid-resistant asthma. Spleen tyrosine kinase (Syk) is activated at high levels in asthma patients and mouse models, and small-molecule Syk inhibitors such as R406 show potent anti-inflammatory effects in the treatment of immune inflammatory diseases. Several downstream signaling molecules of Syk are involved in the glucocorticoid response, so we hypothesized that R406 could restore sensitivity to dexamethasone in severe steroid-resistant asthma.Objective: To discover the role of the Syk inhibitor R406 in glucocorticoid resistance in severe asthma.Methods: Steroid-resistant asthma models were induced by exposure of C57BL/6 mice to house dust mite (HDM) and β-glucan and by TNF-α administration to the bronchial epithelial cell line BEAS-2B. We evaluated the role of the Syk inhibitor R406 in dexamethasone (Dex)-insensitive airway inflammation. Pathological alterations and cytokines in the lung tissues and inflammatory cells in BALF were assessed. We examined the effects of Dex or R406 alone and in combination on the phosphorylation of MAPKs, glucocorticoid receptor (GR) and Syk, as well as the transactivation and transrepression induced by Dex in mouse lung tissues and BEAS-2B cells.Results: Exposure to HDM and β-glucan induced steroid-resistant airway inflammation. The Syk inhibitor R406 plus Dex significantly reduced airway inflammation compared with Dex alone. Additionally, TNF-α-induced IL-8 production in BEAS-2B cells was not completely inhibited by Dex, while R406 markedly promoted the anti-inflammatory effect of Dex. Compared with Dex alone, R406 enhanced Dex-mediated inhibition of the phosphorylation of MAPKs and GR-Ser226 induced by allergens or TNF-α in vivo and in vitro. Moreover, R406 also restored the impaired expression and nuclear translocation of GRα induced by TNF-α. Then, the activation of NF-κB and decreased HDAC2 activity in the asthmatic model were further regulated by R406, as well as the expression of GILZ.Conclusions: The Syk inhibitor R406 improves sensitivity to dexamethasone by modulating GR. This study provides a reference for the development of drugs to treat severe steroid-resistant asthma.

Abstract Background The European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria are widely used in the diagnosis of invasive pulmonary aspergillosis (IPA), but they only apply to immunocompromised patients. We here aimed to identify clinical characteristics helpful to the diagnosis of IPA in non-immunocompromised patients. Methods This is a multicenter retrospective study. Data were collected from adult patients with IPA admitted to 15 tertiary hospitals in China from 2010 to 2016. Results We included 254 patients in the study, of whom 66 (26.0%) were immunocompromised, and 188 (74.0%) were not. Airway-invasion-associated computed tomography (CT) signs including patchy exudation along the airway (67.6% vs. 45.5%, P = 0.001) and thickened airway wall (42.0% vs. 16.7%, P

Background: A novel coronavirus disease 2019 (COVID-19) has caused outbreaks worldwide, and the number of cases is rapidly increasing through human-to-human transmission. Because of the greater transmission capacity and possible subsequent multi-organ damage caused by the virus, it is crucial to understand precisely and manage COVID-19 patients. However, the underlying differences in the clinical features of COVID-19 with and without comorbidities are not fully understood. Aim: The objective of this study was to identify the clinical features of COVID-19 patients with and without complications to guide treatment and predict the prognosis. Method: We collected the clinical characteristics of COVID-19 patients with and without different complications, including hypertension, cardiovascular disease and diabetes. Next, we performed a baseline comparison of each index and traced the dynamic changes in these factors during hospitalization to explore the potential associations. Result: A clinical index of differential expression was used for the regression to select top-ranking factors. The top-ranking clinical characteristics varied in each subgroup, such as indices of liver function, renal function and inflammatory markers. Among them, the indices of renal function were highly ranked in all subgroups and displayed significant differences during hospitalization. Conclusion: Organ functions of COVID-19 patients, particularly renal function, should be cautiously taken care of during management and might be a crucial factor for a poor prognosis of these patients with complications.

Abstract Human paragonimiasis has been appearing all over the world due to increased human migration, international travel, and worldwide food trading. However, delayed and missed diagnosis rates are also increasing due to atypical clinical manifestations and the lack of disease understanding by clinical workers. We describe the case of a 43‐year‐old man, who was hospitalized with cough and chest pain for two months. Chest computed tomography (CT) revealed bilateral emphysema, left pleural effusion, and bilateral atelectasis. The hypereosinophilia gave us a clue; ultimately, the diagnosis of paragonimiasis was made through a diet history and a positive result of serum Paragonimus sp. immunoglobulin (Ig) G antibody. Moreover, 27 misdiagnosed paragonimiasis cases in the past decade have been reported. We draw conclusions by summarizing their characteristics for suspicious eosinophilic paragonimiasis patients; we should inquire diet history carefully, test serum IgG antibodies, and try to detect eggs. Once diagnosed, praziquantel is preferred for treatment.

Abstract Objectives We aimed to gain an understanding of the paradox of the immunity in COVID‐19 patients with T cells showing both functional defects and hyperactivation and enhanced proliferation. Methods A total of 280 hospitalised patients with COVID‐19 were evaluated for cytokine profiles and clinical features including viral shedding. A mouse model of acute infection by lymphocytic choriomeningitis virus (LCMV) was applied to dissect the relationship between immunological, virological and pathological features. The results from the mouse model were validated by published data set of single‐cell RNA sequencing (scRNA‐seq) of immune cells in bronchoalveolar lavage fluid (BALF) of COVID‐19 patients. Results The levels of soluble CD25 (sCD25), IL‐6, IL‐8, IL‐10 and TNF‐α were higher in severe COVID‐19 patients than non‐severe cases, but only sCD25 was identified as an independent risk factor for disease severity by multivariable binary logistic regression analysis and showed a positive association with the duration of viral shedding. In agreement with the clinical observation, LCMV‐infected mice with high levels of sCD25 demonstrated insufficient anti‐viral response and delayed viral clearance. The elevation of sCD25 in mice was mainly contributed by the expansion of CD25+CD8+ T cells that also expressed the highest level of PD‐1 with pro‐inflammatory potential. The counterpart human CD25+PD‐1+ T cells were expanded in BALF of COVID‐19 patients with severe disease compared to those with modest disease. Conclusion These results suggest that high levels of sCD25 in COVID‐19 patients probably result from insufficient anti‐viral immunity and indicate an expansion of pro‐inflammatory T cells that contribute to disease severity.

Microascus species are widely distributed and rarely cause invasive infection in humans. Here we report a case of lung Microascus cirrosus infection in an immunocompetent patient with bronchiectasis. While on systemic voriconazole and aerosolized amphotericin B for three months, the patient's overall condition improved. This case report highlights the possibility of rare pathogen infection occurred in a bronchiectasis patient, as well as the importance of accurate diagnosis and individualized therapy of pulmonary Microascus infection.

Background: Diabetes has been found to increase severity and mortality under the current pandemic of coronavirus disease of 2019 (COVID-19). Up to date, the clinical characteristics of diabetes patients with COVID-19 and the risk factors for poor clinical outcomes are not clearly understood.Methods: The study was retrospectively carried out on enrolled diabetes patients with laboratory confirmed COVID-19 infection from a designated medical center for COVID-19 from January 25th, 2020 to February 14th, 2020 in Wuhan, China. The medical record was collected and reviewed. Univariate and multivariate analyses were performed to assess the risk factors associated with the severe events which were defined as a composite endpoint of admission to intensive care unit, the use of mechanical ventilation, or death.Results: A total of 52 diabetes patients with COVID-19 were finally included in the study. 21 (40.4%) patients had developed severe events in 27.50 (IQR 12.25–35.75) days follow-up, 15 (28.8%) patients experienced life-threatening complications and 8 patients died with a recorded mortality rate of 15.4%. Only 13 patients (41.9%) were in optimal glycemic control with HbA1c value of

The rate of decline in the levels of neutralizing antibodies (NAbs) greatly varies among patients who recover from Coronavirus disease 2019 (COVID-19). However, little is known about factors associated with this phenomenon. The objective of this study is to investigate early factors at admission that can influence long-term NAb levels in patients who recovered from COVID-19. A total of 306 individuals who recovered from COVID-19 at the Tongji Hospital, Wuhan, China, were included in this study. The patients were classified into two groups with high (NAbhigh, n = 153) and low (NAblow, n = 153) levels of NAb, respectively based on the median NAb levels six months after discharge. The majority (300/306, 98.0%) of the COVID-19 convalescents had detected NAbs. The median NAb concentration was 63.1 (34.7, 108.9) AU/mL. Compared with the NAblow group, a larger proportion of the NAbhigh group received corticosteroids (38.8% vs. 22.4%, p = 0.002) and IVIG therapy (26.5% vs. 16.3%, p = 0.033), and presented with diabetes comorbidity (25.2% vs. 12.2%, p = 0.004); high blood urea (median (IQR): 4.8 (3.7, 6.1) vs. 3.9 (3.5, 5.4) mmol/L; p = 0.017); CRP (31.6 (4.0, 93.7) vs. 16.3 (2.7, 51.4) mg/L; p = 0.027); PCT (0.08 (0.05, 0.17) vs. 0.05 (0.03, 0.09) ng/mL; p = 0.001); SF (838.5 (378.2, 1533.4) vs. 478.5 (222.0, 1133.4) μg/L; p = 0.035); and fibrinogen (5.1 (3.8, 6.4) vs. 4.5 (3.5, 5.7) g/L; p = 0.014) levels, but low SpO2 levels (96.0 (92.0, 98.0) vs. 97.0 (94.0, 98.0)%; p = 0.009). The predictive model based on Gaussian mixture models, displayed an average accuracy of 0.7117 in one of the 8191 formulas, and ROC analysis showed an AUC value of 0.715 (0.657–0.772), and specificity and sensitivity were 72.5% and 67.3%, respectively. In conclusion, we found that several factors at admission can contribute to the high level of NAbs in patients after discharge, and constructed a predictive model for long-term NAb levels, which can provide guidance for clinical treatment and monitoring.

To elucidate the regulation of glucocorticoid receptor (GR) signaling under pro-asthmatic conditions, cultured human airway smooth muscle (HASM) cells were treated with proinflammatory cytokines or GR ligands alone and in combination, and then examined for induced changes in ligand-dependent and -independent GR activation and downstream signaling events. Ligand stimulation with either cortisone or dexamethsone (DEX) acutely elicited GR translocation to the nucleus and, comparably, ligand-independent stimulation either with the Th2 cytokine, IL-13, or the pleiotropic cytokine combination, IL-1β/TNFα, also acutely evoked GR translocation. The latter response was potentiated by combined exposure of cells to GR ligand and cytokine. Similarly, treatment with either DEX or IL-13 alone induced GR phosphorylation at its serine-211 residue (GR(Ser211)), denoting its activated state, and combined treatment with DEX+IL-13 elicited heightened and sustained GR(Ser211) phosphorylation. Interestingly, the above ligand-independent GR responses to IL-13 alone were not associated with downstream GR binding to its consensus DNA sequence or GR transactivation, whereas both DEX-induced GR:DNA binding and transcriptional activity were significantly heightened in the presence of IL-13, coupled to increased recruitment of the transcriptional co-factor, MED14. The stimulated GR signaling responses to DEX were prevented in IL-13-exposed cells wherein GR(Ser211) phosphorylation was suppressed either by transfection with specific serine phosphorylation-deficient mutant GRs or treatment with inhibitors of the MAPKs, ERK1/2 and JNK. Collectively, these novel data highlight a heretofore-unidentified homeostatic mechanism in HASM cells that involves pro-asthmatic cytokine-driven, MAPK-mediated, non-ligand-dependent GR activation that confers heightened glucocorticoid ligand-stimulated GR signaling. These findings raise the consideration that perturbations in this homeostatic cytokine-driven GR signaling mechanism may be responsible, at least in part, for the insensirtivity to glucocorticoid therapy that is commonly seen in individuals with severe asthma.

Graphite carbon nitride (CN) eliminates cancer cells by converting H2O2 to highly toxic •OH under visible light. However, its in vivo applications are constrained by insufficient endogenous H2O2, accumulation of OH− and finite photocarriers. We designed Fe/NV-CN, co-modified CN with nitrogen vacancies (NV) and ferric ions (Fe3+). NV and Fe3+, not only adjust the band structure of CN through quantum confinement effect and the altered coupled oscillations of atomic orbitals to facilitates •OH production by oxidizing OH−, but also construct dual carrier-transfer channels for electrons and holes to respective active sites by introducing stepped electrostatic potential and shortening three-electron bonds, thereby involving more carriers in •OH production. Fe/NV-CN, the novel reactor, effectually produces vast •OH under illumination by expanding OH− as the raw material of •OH and augmenting carriers at active sites, which induces cancer cell apoptosis by disrupting mitochondrial function for significant shrinkage of Cal27 cell-induced tumor under illumination. This work provides not only an effective photosensitizer avoiding the accumulation of OH− for cancer therapy but also a novel strategy by constructing dual carrier-transfer channels on semiconductor photosensitizers for improving the therapeutic effect of photodynamic therapy.