Presepsin as a prognostic biomarker in COVID-19 patients: combining clinical scoring systems and laboratory inflammatory markers for outcome prediction.

BACKGROUND: There is still limited research on the prognostic value of Presepsin as a biomarker for predicting the outcome of COVID-19 patients. Additionally, research on the combined predictive value of Presepsin with clinical scoring systems and inflammation markers for disease prognosis is lacking. METHODS: A total of 226 COVID-19 patients admitted to Beijing Youan Hospital's emergency department from May to November 2022 were screened. Demographic information, laboratory measurements, and blood samples for Presepsin levels were collected upon admission. The predictive value of Presepsin, clinical scoring systems, and inflammation markers for 28-day mortality was analyzed. RESULTS: A total of 190 patients were analyzed, 83 (43.7%) were mild, 61 (32.1%) were moderate, and 46 (24.2%) were severe/critically ill. 23 (12.1%) patients died within 28 days. The Presepsin levels in severe/critical patients were significantly higher compared to moderate and mild patients (p < 0.001). Presepsin showed significant predictive value for 28-day mortality in COVID-19 patients, with an area under the ROC curve of 0.828 (95% CI: 0.737-0.920). Clinical scoring systems and inflammation markers also played a significant role in predicting 28-day outcomes. After Cox regression adjustment, Presepsin, qSOFA, NEWS2, PSI, CURB-65, CRP, NLR, CAR, and LCR were identified as independent predictors of 28-day mortality in COVID-19 patients (all p-values < 0.05). Combining Presepsin with clinical scoring systems and inflammation markers further enhanced the predictive value for patient prognosis. CONCLUSION: Presepsin is a favorable indicator for the prognosis of COVID-19 patients, and its combination with clinical scoring systems and inflammation markers improved prognostic assessment.

Serum S1P level in interstitial lung disease (ILD) is a potential biomarker reflecting the severity of pulmonary function.

BACKGROUND: sphingosine-1-phosphate (S1P), a naturally occurring sphingolipid, has been involved in pulmonary interstitial remodeling signaling. However, no study has examined its clinical merits for interstitial lung disease (ILD). This study aimed to investigate the serum level of S1P in ILD patients and its clinical correlation with the severity of disease in the two main types of ILDs: the IPF and the CTD-ILD patients. METHODS: This retrospective observational pilot study included 67 ILD patients and 26 healthy controls. These patients were stratified into the IPF group (35) and the CTD-ILD group (32). The severity of ILD was evaluated through pulmonary function indicators and the length of hospital stay. RESULTS: Serum S1P level was statistically higher in ILD patients than in health control (p = 0.002), while the Serum S1P levels in CTD-ILD and IPF patients were comparable. Serum S1P level further showed statistically negative correlation with pulmonary function indexes (TLC% pred, FVC% pred and FEV1% pred) and positive correlation with length of hospital stay (r = -0.38, p = 0.04; r = -0.41, p = 0.02, r = -0.37, p = 0.04; r = 0.42, p = 0.02, respectively) in CTD-ILD patients, although serum S1P level was not significantly correlated with inflammatory indexes. The IPF patients failed to exhibit a significant correlation of serum S1P level with pulmonary function and length of hospital stay. CONCLUSIONS: Serum S1P level might be a clinically useful biomarker in evaluating the severity of CTD-ILD patients rather than IPF patients.

TGFß1-RCN3-TGFBR1 loop facilitates pulmonary fibrosis by orchestrating fibroblast activation.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) bears high mortality due to unclear pathogenesis and limited therapeutic options. Therefore, identifying novel regulators is required to develop alternative therapeutic strategies. METHODS: The lung fibroblasts from IPF patients and Reticulocalbin 3 (RCN3) fibroblast-selective knockdown mouse model were used to determine the importance of Rcn3 in IPF; the epigenetic analysis and protein interaction assays, including BioID, were used for mechanistic studies. RESULTS: Reticulocalbin 3 (RCN3) upregulation is associated with the fibrotic activation of lung fibroblasts from IPF patients and Rcn3 overexpression blunts the antifibrotic effects of pirfenidone and nintedanib. Moreover, repressing Rcn3 expression in mouse fibroblasts ameliorates bleomycin-induced lung fibrosis and pulmonary dysfunction in vivo. Mechanistically, RCN3 promotes fibroblast activation by maintaining persistent activation of TGFß1 signalling via the TGFß1-RCN3-TGFBR1 positive feedback loop, in which RCN3 upregulated by TGFß1 exposure detains EZH2 (an epigenetic methyltransferase) in the cytoplasm through RCN3-EZH2 interaction, leading to the release of the EZH2-H3K27me3 epigenetic repression of TGFBR1 and the persistent expression of TGFBR1. CONCLUSIONS: These findings introduce a novel regulating mechanism of TGFß1 signalling in fibroblasts and uncover a critical role of the RCN3-mediated loop in lung fibrosis. RCN3 upregulation may cause resistance to IPF treatment and targeting RCN3 could be a novel approach to ameliorate pulmonary fibrosis.

Clinical characteristics of adult inpatients with Measles in Beijing from 2010 to 2021: a retrospective analysis.

BACKGROUND: With the measles vaccine coverage rate gradually increasing, adult patients' epidemiological and clinical characteristics have changed. AIMS: To analyze the clinical characteristics of adult measles patients in Beijing Youan Hospital. METHODS: We retrospectively reviewed the electronic medical records of 818 patients diagnosed with measles at Beijing Youan Hospital between June 2010 and October 2021. We divided all hospitalized patients into two demographics groups, using 14 years of age as the cut-off. RESULTS: Of the adult inpatients, 110 (74.83%) were aged 20-40. There was an overall peak incidence in 2014, and yearly peaks came in April. Fever, cough, erythema, and Koplik's spots were present in 79.59%, 82.1%, 99.3%, and 59.8% of the adult group, respectively, compared to 75.26%, 92.0%, 99.9%, and 39.0% of the pediatric group. Decreased lymphocytes and hepatic impairment were common in adults. The adult group's median level of C-reactive protein was higher than that of the pediatric group (p < 0.05). The positive rate of measles antibody (IgM) detection was 64.6% in the adults and 78.8% in the pediatric group (p < 0.05). Of the adults, 46.9%, 8.8%, and 66% had pneumonia, gastroenteritis, and antibiotic use, compared to 89.6%, 2.7%, and 83.2% of the pediatric patients. The duration of symptoms before admission and the average length of hospital stay was approximately six days in both groups. CONCLUSIONS: Koplik's spots are more likely to be detected by clinicians in adult patients admitted to the hospital. Active surveillance is helpful for adults who are negative for IgM on admission. Although the proportion of adult measles patients with liver injury is high, the disease is generally mild. Measles significantly impacts peripheral blood lymphocytes in adults, but adults are at lower risk of concurrent pneumonia than the pediatric group. Clinicians need to pay attention to the appropriate use of antibiotics. Expanding the coverage of the measles vaccination in high-risk areas is beneficial for preventing measles in adults.

Serum Rcn3 level is a potential diagnostic biomarker for connective tissue disease-associated interstitial lung disease and reflects the severity of pulmonary function.

BACKGROUND: Although reticulocalbin 3 (Rcn3) has a critical role in alveolar epithelial function as well as in pathogenesis of pulmonary fibrosis, no study has yet examined its diagnostic and prognostic values for interstitial lung disease (ILD). This study aimed to evaluate Rcn3 as a potential marker in differential diagnosis of idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD) and in reflecting the severity of disease. METHODS: This was a retrospective observational pilot study included 71 ILD patients and 39 healthy controls. These patients were stratified into IPF group (39) and CTD-ILD group (32). The severity of ILD was evaluated through pulmonary function test. RESULTS: Serum Rcn3 level was statistically higher in CTD-ILD patients than that in IPF patients (p = 0.017) and healthy controls (p = 0.010). Serum Rcn3 further showed statistically negative correlation with pulmonary function indexes (TLC% pred and DLCO% pred) and positive correlation with inflammatory indexes (CRP and ESR) (r = - 0.367, p = 0.039; r = - 0.370, p = 0.037; r = 0.355, p = 0.046; r = 0.392, p = 0.026, respectively) in CTD-ILD patients rather than IPF patients. ROC analysis demonstrated that serum Rcn3 had superior diagnostic value for CTD-ILD and a cutoff value of 2.73 ng/mL had a sensitivity of 69%, a specificity of 69% and an accuracy of 45% for diagnose of CTD-ILD. CONCLUSIONS: Serum Rcn3 levels might be a clinically useful biomarker in screening and evaluating CTD-ILD.

Peripheral immune phenotypes and T cell receptor repertoire in pneumocystis pneumonia in HIV-1 infected patients.

BACKGROUND: The host immune response to pneumocystis pneumonia (PCP) involves interactions among immune cell subsets and cytokines. However, the definite pathogenesis and immunological influences of P. jirovecii have not been fully elucidated. METHODS: Mass cytometry and high-throughput sequencing of the T cell receptor (TCR) were used to profile the host immune response to human immunodeficiency virus-1 (HIV-1) and P. jirovecii infection. RESULTS: Our findings demonstrated that patients with PCP showed different immune cell proportions when compared to healthy controls. Changes in cytokines were found after anti-PCP treatment, suggested that cytokines may play an important role in controlling the pathogen. Furthermore, PCP patients showed marked reduction of TCR repertoire diversity. The diversity of TCR repertoire was restored by the anti-PCP treatment. CONCLUSION: In summary, we profiled the composition and characteristics of immune environment in response to HIV-1 and P. jirovecii infection, which may contribute to elucidating host immunity.

Reticulocalbin 3 deficiency in alveolar epithelium attenuated LPS-induced ALI via NF-κB signaling.

Acute respiratory distress syndrome (ARDS) is characterized by acute lung injury (ALI) secondary to an excessive alveolar inflammatory response. Reticulocalbin 3 (Rcn3) is an endoplasmic reticulum (ER) lumen protein in the secretory pathway. We previously reported the indispensable role of Rcn3 in type II alveolar epithelial cells (AECIIs) during lung development and the lung injury repair process. In the present study, we further observed a marked induction of Rcn3 in the alveolar epithelium during LPS-induced ALI. In vitro alveolar epithelial (MLE-12) cells consistently exhibited a significant induction of Rcn3 accompanied with NF-κB activation in response to LPS exposure. We examined the role of Rcn3 in the alveolar inflammatory response by using mice with a selective deletion of Rcn3 in alveolar epithelial cells upon doxycycline administration. The Rcn3 deficiency significantly blunted the ALI and alveolar inflammation induced by intratracheal LPS instillation but not that induced by an intraperitoneal LPS injection (secondary insult); the alleviated ALI was accompanied by decreases in NF-κB activation and NLRP3 levels but not in GRP78 and cleaved caspase-3 levels. The studies conducted in MLE-12 cells consistently showed that Rcn3 knockdown blunted the activations of NF-κB signaling and NLRP3-dependent inflammasome upon LPS exposure. Collectively, these findings suggest a novel role for Rcn3 in regulating the alveolar inflammatory response to pulmonary infection via the NF-κB/NLRP3/inflammasome axis and shed additional light on the mechanism of ARDS/ALI.

Prevention of SARS-CoV-2 transmission from international arrivals: Xiaotangshan Designated Hospital, China.

A surge in the number of international arrivals awaiting coronavirus disease 2019 (COVID-19) screening overwhelmed health-care workers and depleted medical resources in designated hospitals in Beijing, China in March 2020. The People's Government of Beijing Municipality therefore issued a policy which required the mandatory transfer of all asymptomatic passengers arriving from a foreign country to designated quarantine hotels, and the transfer of passengers with fever or respiratory symptoms to designated hospitals. Xiaotangshan Designated Hospital, a severe acute respiratory syndrome hospital in 2003, was rapidly renovated and put into operation with the main tasks of screening and isolating symptomatic international arrivals at Beijing Capital International Airport, providing basic medical care for mild to moderate COVID-19-positive cases, and rapidly referring severe to critical COVID-19-positive cases to higher-level hospitals. During the month-long period of its operation, 2171 passengers were screened and 53 were confirmed as having COVID-19 (six severe to critical). We describe how the use of Xiaotangshan Designated Hospital in this way enabled the efficient grouping and assessment of passengers arriving from a foreign country, the provision of optimal patient care without compromising public safety and the prioritization of critically ill patients requiring life-saving treatment. The designated hospital is a successful example of the World Health Organization's recommendation to renovate existing medical infrastructures to improve the COVID-19 response capacity. The flexible design of Xiaotangshan Designated Hospital means that it can be repurposed and reopened at any time to respond to the changing pandemic conditions.

En mars 2020, la brusque hausse du nombre d'arrivées internationales en attente de dépistage de la maladie à coronavirus 2019 (COVID-19) a submergé les professionnels de la santé et épuisé les ressources médicales dans les hôpitaux de référence à Beijing, en Chine. Le gouvernement populaire de la municipalité de Beijing a réagi en ordonnant que tous les passagers asymptomatiques en provenance d'un pays étranger soient transférés vers des hôtels reconvertis en centres de quarantaine, et que ceux manifestant de la fièvre ou des symptômes respiratoires soient envoyés dans des hôpitaux de référence. L'hôpital de référence Xiaotangshan, construit en 2003 pour lutter contre le syndrome respiratoire aigu sévère, a rapidement été rénové et mis en service. Ses tâches principales: dépister et isoler les passagers internationaux symptomatiques débarquant au Beijing Capital International Airport, prodiguer les soins médicaux de base aux cas positifs de COVID-19 souffrant d'une forme légère à modérée, et adresser dès que possible les cas positifs de COVID-19 dans un état grave ou critique aux hôpitaux spécialisés. En l'espace d'un mois, 2171 passagers ont été testés et 53 se sont révélés positifs à la COVID-19 (6 étant dans un état grave ou critique). Nous décrivons la façon dont l'hôpital de référence Xiaotangshan a ainsi permis de regrouper et d'évaluer efficacement les arrivées en provenance de l'étranger, d'offrir une prise en charge optimale des patients sans compromettre la sécurité publique, et d'établir des priorités afin que les malades gravement atteints puissent bénéficier d'un traitement dans les plus brefs délais. Cet hôpital de référence est un exemple réussi de la mise en œuvre de la recommandation formulée par l'Organisation mondiale de la Santé: rénover les infrastructures médicales existantes afin d'améliorer les capacités de lutte contre la COVID-19. Grâce à sa conception flexible, l'hôpital Xiaotangshan peut être réutilisé et rouvert à n'importe quel moment pour réagir à un contexte pandémique en perpétuelle évolution.

Un aumento del número de llegadas de vuelos internacionales en espera de la detección del coronavirus 2019 (COVID-19) sobrecargó al personal sanitario y agotó los recursos médicos en los hospitales designados de Pekín (China) en marzo de 2020. Por lo tanto, la policía del Gobierno Popular del municipio de Pekín se tuvo que hacer cargo del traslado obligatorio de todos los pasajeros asintomáticos que llegaran de un país extranjero a los hoteles de cuarentena designados, y el traslado de los pasajeros con fiebre o síntomas respiratorios a los hospitales designados. El hospital designado de Xiaotangshan, un hospital especializado en el síndrome respiratorio agudo severo en 2003, se rehabilitó rápidamente y se puso en funcionamiento con las tareas principales de examinar y aislar a los sintomáticos que llegaban al Aeropuerto Internacional de Pekín, proporcionando atención médica básica a los casos positivos de COVID-19 de leves a moderados, y derivando rápidamente los casos positivos de COVID-19 de graves a críticos a hospitales de nivel superior. Durante el mes que duró su funcionamiento, se examinó a 2.171 pasajeros y se confirmó que 53 tenían la COVID-19 (6 de ellos con intensidad de grave a crítica). Describimos cómo el uso del hospital designado de Xiaotangshan permitió agrupar y evaluar eficazmente a los pasajeros que llegaban de un país extranjero, prestar una atención óptima a los pacientes sin comprometer la seguridad pública y priorizar a los pacientes en estado crítico que requerían tratamiento para salvar su vida. El hospital designado es un ejemplo de éxito de la recomendación de la Organización Mundial de la Salud de renovar las infraestructuras médicas existentes para mejorar la capacidad de respuesta ante la COVID-19. El diseño flexible del hospital designado de Xiaotangshan significa que puede utilizarse y volver a habilitarse en cualquier momento para responder a las condiciones cambiantes de la pandemia.

A mass in the upper abdomen derived from Talaromyces marneffei infected lymphadenopathy: a case report.

BACKGROUND: An upper abdominal mass without tenderness often indicates a benign or malignant tumor once liver or spleen hyperplasia has been excluded. A lymphadenopathic mass from Talaromyces marneffei infection is rare. CASE PRESENTATION: We report the case of a 29-year-old human immunodeficiency virus (HIV) infected man who presented with an upper abdominal mass and without any symptoms related with infection. Histopathology and next-generation sequencing (NGS) following biopsy of the mass confirmed T. marneffei-infected lymphadenopathy, and the patient was successfully treated with amphotericin B and itraconazole. CONCLUSIONS: This case report suggests that potential fungal infection should be considered during the diagnostic workup of a mass in clinical practice.

Dynamics of Detection of Anti-SARS-CoV-2 IgG/IgM and SARS-CoV-2 RNA in Respiratory Tract Specimens in 48 COVID-19 Patients.

BACKGROUND: The rapid spread of pneumonia caused by SARS-CoV-2 has seriously threatened people. In this study, we detected the expression of anti-SARS-CoV-2 IgG/IgM and respiratory tract SARS-CoV-2 RNA in patients with COVID-19 and explored the correlation and clinical significance between SARS-CoV-2 antibody and respiratory SARS-CoV-2 RNA. METHODS: From March 5, 2020 to April 28, 2020, 48 cases with COVID-19 diagnosed in Beijing Xiaotangshan Hospital were enrolled. SARS-CoV-2 RNAs were detected by real-time fluorescence RT-PCR method. Serum SARS-CoV-2 IgG/IgM antibodies were determined by colloidal gold immunochromatography. The statistical analysis was performed using chi-squared test. RESULTS: In all the patients, SARS-CoV-2 RNA among 270 upper respiratory tract (nasal or throat swabs) samples, 71 lower respiratory tract (sputum) samples, and anti-SARS-CoV-2 IgM/IgG antibodies in 123 serum samples were detected during the hospitalization period. The positive rate of anti-SARS-CoV-2 IgG was significantly higher than that of anti-SARS-CoV-2 IgM within the first week after symptom onset (p < 0.05). The positive rate of anti-SARS-CoV-2 IgG was also significantly higher than that of anti-SARS-CoV-2 IgM during day 8 - 30 after symptom onset (p < 0.01). The positive rate of SARS-CoV-2 RNA in the lower respiratory tract specimens (64.8%, 46/71) was significantly higher than that in the upper respiratory tract (46.7%, 126/270) (p < 0.05). The positive rate (100%, 4/4) of SARS-CoV-2 RNA detection in the lower respiratory tract specimens before IgG seroconversion was significantly higher than that of the positive rate (59.3%, 32/54) after IgG seroconversion (p < 0.01). The positive rate (72.2%, 57/79) of SARS-CoV-2 RNA detection in the upper respiratory tract specimens before IgG seroconversion was significantly higher than that of the positive rate (30.7%, 39/127) after IgG seroconversion (p < 0.01). CONCLUSIONS: Anti-SARS-CoV-2 IgG might be detected within the first week after symptom onset. The application of SARS-CoV-2 antibody (IgG/IgM) detection is important for the suspected cases of SARS-CoV-2 infection with negative SARS-CoV-2 RNA results. The positive rate of SARS-CoV-2 RNA detection in the lower respiratory tract specimens was significantly higher than that in the upper respiratory tract. Sputum detection is recommended for the detection of SARS-CoV-2 RNA. Using lower respiratory tract specimens may reduce the false negative PCR tests. The detection of SARS-CoV-2 RNA can be improved by investigating follow-up specimens over time.

Early prediction of acute kidney injury after liver transplantation by scoring system and decision tree.

BACKGROUND AND AIMS: Early detection of acute kidney injury (AKI) is crucial for the prognosis of patients after liver transplantation (LT). This passage aims to analyze the perioperative clinical markers of AKI after LT and establish predictive models based on clinical variables for early detection of AKI after LT. METHODS: We prospectively collected 109 patients with LT, and compared the differences of perioperative clinical markers between the AKI group and non-AKI group. The scoring system and decision tree model were established through the risk factors. Another 163 patients who underwent LT in the same center from 2017 to 2018 were retrospectively collected to verify the models. RESULTS: In multiple comparisons of risk factors of post-LT AKI, pre-operative factors were excluded automatically, intraoperative and post-operative factors including operating time, intraoperative hypotension time, post-operative infection, the peak of post-operative AST, and post-operative shock were the independent risk factors for post-LT AKI. The scoring system established with the risk factors has good predictive power (AUC = 0.755) in the validation cohort. The decision tree also shows that post-operative shock was the most important marker, followed by post-operative infection. CONCLUSION: Five intraoperative and post-operative factors are independently associated with post-LT AKI rather than pre-operative factors, which indicates that operation technique and post-operative management may more important for the prevention of post-LT AKI. The scoring system and decision tree model could complement each other, and provide quantitative and intuitive prediction tools for clinical practice of early detection of post-LT AKI.

The HDL from septic-ARDS patients with composition changes exacerbates pulmonary endothelial dysfunction and acute lung injury induced by cecal ligation and puncture (CLP) in mice.

BACKGROUND: Septic-acute respiratory distress syndrome (ARDS), characterized by the acute lung injury (ALI) secondary to aberrant systemic inflammatory response, has high morbidity and mortality. Despite increased understanding of ALI pathogenesis, the therapies to prevent lung dysfunction underlying systemic inflammatory disorder remain elusive. The high density lipoprotein (HDL) has critical protective effects in sepsis and its dysfunction has a manifested contribution to septic organ failure. However, the adverse changes in HDL composition and function in septic-ARDS patients are large unknown. METHODS: To investigate HDL remodeling in septic-ARDS, we analyzed the changes of HDL composition from 40 patients with septic-ARDS (A-HDL) and 40 matched normal controls (N-HDL). To determine the deleterious functional remodeling of HDL, A-HDL or N-HDL was administrated to C57BL/6 and apoA-I knock-out (KO) mice after cecal ligation and puncture (CLP) procedure. Mouse lung microvascular endothelial cells (MLECs) were further treated by these HDLs to investigate whether the adverse effects of A-HDL were associated with endothelial dysfunction. RESULTS: Septic-ARDS patients showed significant changes of HDL composition, accompanied with significantly decreased HDL-C. We further indicated that A-HDL treatment aggravated CLP induced ALI. Intriguingly, these deleterious effects of A-HDL were associated with pulmonary endothelial dysfunction, rather than the increased plasma lipopolysaccharide (LPS). Further in vitro results demonstrated the direct effects of A-HDL on MLECs, including increased endothelial permeability, enhanced expressions of adhesion proteins and pro-inflammatory cytokines via activating NF-κB signaling and decreased junction protein expression. CONCLUSIONS: Our results depicted the remodeling of HDL composition in sepsis, which predisposes lung to ARDS via inducing ECs dysfunction. These results also demonstrated the importance of circulating HDL in regulating alveolar homeostasis.

Reticulocalbin 3 Deficiency in Alveolar Epithelium Exacerbated Bleomycin-induced Pulmonary Fibrosis.

Reticulocalbin 3 (Rcn3) is an endoplasmic reticulum (ER) lumen protein localized to the secretory pathway. We have reported that Rcn3 plays a critical role in alveolar epithelial type II cell maturation during perinatal lung development, but its biological role in the adult lung is largely unknown. In this study, we found marked induction of Rcn3 expression in alveolar epithelium during bleomycin-induced pulmonary fibrosis, which is most obvious in alveolar epithelial type II cells (AECIIs). To further examine Rcn3 in pulmonary injury remodeling, we generated transgenic mice to selectively delete Rcn3 in AECIIs in adulthood. Although Rcn3 deletion did not cause obvious abnormalities in the lung architecture and mechanics, the exposure of Rcn3-deleted mice to bleomycin led to exacerbated pulmonary fibrosis and reduced lung mechanics. These Rcn3-deleted mice also displayed enhanced alveolar epithelial cell (AEC) apoptosis and ER stress after bleomycin treatment, which was confirmed by in vitro studies both in primary AECIIs and mouse lung epithelial cells. Consistently, Rcn3 deficiency also enhanced ER stress and apoptosis induced by ER stress inducers, tunicamycin and thapsigargin. In addition, Rcn3 deficiency caused blunted wound closure capability of AECs, but not altered proliferation and bleomycin-induced epithelial-mesenchymal transition process. Collectively, these findings indicate that bleomycin-induced upregulation of Rcn3 in AECIIs appears to contribute to AECII survival and wound healing. These observations, for the first time, suggest a novel role of Rcn3 in regulating pulmonary injury remodeling, and shed additional light on the mechanism of idiopathic pulmonary fibrosis.

Changes of Lymphocyte Subgroups in Non-Small Cell Lung Cancer Patients Before and During Chemotherapy.

BACKGROUND: The aim of this study was to analyse changes in the lymphocyte subgroups of non-small cell lung cancer (NSCLC) patients before and during four cycles of chemotherapy. METHODS: NSCLC patients (n = 32) who were undergoing their initial chemotherapy or had finished their final chemotherapy ≥ three months ago were enrolled. The patients were divided into demographic subgroups. Lymphocyte subgroups (n = 13) were examined via flow cytometry before and during chemotherapy (9 time points). RESULTS: NSCLC patients exhibited overall decreases in lymphocyte subgroups during chemotherapy. Most of the subgroups increased slightly before the second cycle of chemotherapy but decreased afterwards compared with pre-chemotherapy levels. Significant decreases (p < 0.05) were observed in lymphocyte subgroups starting at the third cycle of chemotherapy. In the first efficacy assessment, CD4+ and CD8+CD28+ levels in the tumour control group were significantly higher compared with the tumour progression group (p < 0.05). The first and second efficacy assessments revealed that the DC1/DC2 levels in the tumour progression group on the last day of the first cycle and the ninth day of the second cycle were significantly higher compared with the tumour control group (p < 0.05), and the CD4+/CD8+ level in the non-surgery group was significantly higher compared with the surgery group (p < 0.05). CONCLUSIONS: The immune functions of NSCLC patients began to decrease beginning in the second cycle of chemotherapy. During the third and fourth cycles of chemotherapy, immune function was decreased significantly compared with pre-chemotherapy levels. CD4+, CD8+CD28+, and DC1/DC2 cells were associated with tumour progression, representing new biomarkers for chemotherapeutic efficacy in NSCLC.

Mitochondrial Metabolism in Alveolar Macrophages of Patients Infected with HIV, Tuberculosis, and HIV/Tuberculosis.

Tuberculosis (TB) is one of the most common opportunistic infections and is a leading cause of mortality in patients with HIV and AIDS. HIV infection causes serious defects in the host immune system and increases the risk of active TB. TB infection promotes HIV replication and aggravates host damage in patients with HIV/AIDS. Alveolar macrophages (AMs) are essential immune cells during TB and HIV infections. AMs undergo a shift in mitochondrial metabolism during TB or HIV infection, that is, metabolic reprogramming, allowing them to act in the form of classical activated macrophages (M1) and alternative activated macrophages (M2) at different stages of infection. We reviewed the alterations in the mitochondrial energy metabolism of AMs in patients with HIV, TB, and HIV/TB to provide ideas for further research on the role of metabolic reprogramming by AMs in the pathogeneses of HIV, TB, and HIV/TB coinfection.

sTREM-1 as a Predictive Biomarker for Disease Severity and Prognosis in COVID-19 Patients.

Background: Research on biomarkers associated with the severity and adverse prognosis of COVID-19 can be beneficial for improving patient outcomes. However, there is limited research on the role of soluble TREM-1 (sTREM-1) in predicting the severity and prognosis of COVID-19 patients. Methods: A total of 115 COVID-19 patients admitted to the emergency department of Beijing Youan Hospital from February to May 2023 were included in the study. Demographic information, laboratory measurements, and blood samples for sTREM-1 levels were collected upon admission. Results: Our study found that sTREM-1 levels in the plasma of COVID-19 patients increased with the severity of the disease (moderate vs mild, p=0.0013; severe vs moderate, p=0.0195). sTREM-1 had good predictive value for disease severity and 28-day mortality (area under the ROC curve was 0.762 and 0.805, respectively). sTREM-1 also exhibited significant correlations with age, body temperature, respiratory rate, PaO2/FiO2, PCT, CRP, and CAR. Ultimately, through multivariate logistic regression analysis, we determined that sTREM-1 (OR 1.008, 95% CI: 1.002-1.013, p=0.005), HGB (OR 0.966, 95% CI: 0.935-0.998, p=0.036), D-dimer (OR 1.001, 95% CI: 1.000-1.001, p=0.009), and CAR (OR 1.761, 95% CI: 1.154-2.688, p=0.009) were independent predictors of 28-day mortality in COVID-19 patients. The combination of these four markers yielded a strong predictive value for 28-day mortality in COVID-19 cases with an AUC of 0.919 (95% CI: 0.857 -0.981). Conclusion: sTREM-1 demonstrated good predictive value for disease severity and 28-day mortality, serving as an independent prognostic factor for adverse patient outcomes. In the future, we anticipate conducting large-scale multicenter studies to validate our research findings.

Impact of Lianhua Qingwen on viral shedding in omicron mild/asymtomatic patients: a real-world study.

Background: Lianhuaqingwen (LHQW), a traditional Chinese medicine comprised of 13 herbal extracts renowned for their robust heat-clearing and detoxifying properties, has gained widespread utilization in China but has yet to garner similar recognition abroad. It is believed to exhibit efficacy in ameliorating symptoms in individuals afflicted with coronavirus disease 2019 (COVID-19). However, the precise impact of LHQW on viral shedding (VS), particularly in the context of mild or asymptomatic infections caused by the Omicron BF.4/5 or BF.7 variants of COVID-19, remained inadequately elucidated. Consequently, a real-world study was conducted, involving patients diagnosed with COVID-19, with the primary objective of ascertaining the effectiveness of LHQW in this specific clinical context. Methods: We conducted an investigation on Omicron-infected patients through a single-center, propensity score-matched real-world study conducted at Xiaotangshan Fangcang Hospital from May to November 2022. A total of 3,368 COVID-19 patients were enrolled in the study, all of whom presented mild or asymptomatic infections caused by either BF.4/5 or BF.7 strains of the virus. Demographic and clinical data were systematically collected from medical records. Patients were allocated to receive treatment with LHQW (designated as the treatment group) or received no LHQW treatment (designated as the not-treated/no-treatment group). Viral load was quantified utilizing quantitative real-time PCR (qPCR), and the duration of VS was defined as the time interval between the initial negative test result and the date of COVID-19 diagnosis or symptom onset. Results: The study encompassed a cohort of 3,368 patients, and following propensity score matching, a subset of 296 patients was meticulously chosen for subsequent analysis. Notably, baseline characteristics exhibited disparities between the treatment and not-treated/no-treatment groups. However, post-matching, these characteristics achieved a commendable level of comparability. Our findings unequivocally demonstrated that there existed no statistically significant disparity in VS. This holds true when comparing patients subjected to LHQW treatment against those not administered LHQW, as well as when contrasting individuals presenting asymptomatic and mild COVID-19 manifestations. Conclusion: No statistically significant difference in VS was observed between patients who underwent LHQW treatment and those who did not. Additional investigations are imperative to provide a comprehensive assessment of LHQW's efficacy, particularly in patients afflicted with severe COVID-19 or those infected with viral strains distinct from BF.4/5 or BF.7.

A robust web-based tool to predict viral shedding in patients with Omicron SARS-CoV-2 variants.

Background: Data on viral kinetics and variants affecting the duration of viral shedding were limited. Our objective was to determine viral shedding in distinct severe acute respiratory syndrome coronavirus 2 variants, including Omicron BA.4/5 and BF.7, and to identify the relevant influencing factors. Methods: We carried out a longitudinal cohort study at Beijing Xiaotangshan Fangcang shelter hospital from May to June 2022 (Omicron BA.4/5) and from November to December 2022 (Omicron BF.7). Nucleocapsid protein (N) and open reading frame (ORF) genes were considered as the target genes of the reverse transcription PCR. The daily results of cycle threshold (CT), including lowest ORF1ab-CT values for days 1-3 post-hospitalisation and lowest N-CT values for days 1-3 post-hospitalisation (CT3minN) and demographic and clinical characteristics were collected. Results: 1433 patients with coronavirus disease 2019 (COVID-19) were recruited from the Fangcang shelter hospital, in which 278 patients were diagnosed with Omicron BA.4/5 and 1155 patients with Omicron BF.7. Patients with BF.7 infection showed a longer duration of viral shedding. The duration of viral shedding was associated with the variants age, alcohol use, the severity of COVID-19 and CT3minN. Moreover, the nomogram had excellent accuracy in predicting viral shedding. Conclusions: Our results indicated that patients with Omicron BF.7 had a longer period of contagiousness than those with BA.4/5. The duration of viral shedding was affected by a variety of factors and the nomogram may become an applicable clinical instrument to predict viral shedding. Furthermore, we developed a new COVID-19 viral shedding predicting model that can accurately predict the duration of viral shedding for COVID-19, and created a user-friendly website to apply this prediction model (https://puh3.shinyapps.io/CVSP_Model/).

Oral VV116 versus placebo in patients with mild-to-moderate COVID-19 in China: a multicentre, double-blind, phase 3, randomised controlled study.

BACKGROUND: Spread of SARS-CoV-2 led to a global pandemic, and there remains unmet medical needs in the treatment of Omicron infections. VV116, an oral antiviral agent that has potent activity against SARS-CoV-2, was compared with a placebo in this phase 3 study to investigate its efficacy and safety in patients with mild-to-moderate COVID-19. METHODS: This multicentre, double-blind, phase 3, randomised controlled study enrolled adults in hospitals for infectious diseases and tertiary general hospitals in China. Eligible patients were randomly assigned in a 1:1 ratio using permuted block randomisation to receive oral VV116 (0·6 g every 12 h on day 1 and 0·3 g every 12 h on days 2-5) or oral placebo (on the same schedule as VV116) for 5 days. Randomisation stratification factors included SARS-CoV-2 vaccination status and the presence of high-risk factors for progression to severe COVID-19. Inclusion criteria were a positive SARS-CoV-2 test, an initial onset of COVID-19 symptoms 3 days or less before the first study dose, and a score of 2 or more for any target COVID-19-related symptoms in the 24 h before the first dose. Patients who had severe or critical COVID-19 or who had taken any antiviral drugs were excluded from the study. The primary endpoint was the time to clinical symptom resolution for 2 consecutive days. Efficacy analyses were performed on a modified intention-to-treat population, comprising all patients who received at least one dose of VV116 or placebo, tested positive for SARS-CoV-2 nucleic acid, and did not test positive for influenza virus before the first dose. Safety analyses were done on all participants who received at least one dose of VV116 or placebo. This study was registered with ClinicalTrials.gov, NCT05582629, and has been completed. FINDINGS: A total of 1369 patients were randomly assigned to treatment groups and 1347 received either VV116 (n=674) or placebo (n=673). At the interim analysis, VV116 was superior to placebo in reducing the time to sustained clinical symptom resolution among 1229 patients (hazard ratio [HR] 1·21, 95% CI 1·04-1·40; p=0·0023). At the final analysis, a substantial reduction in time to sustained clinical symptom resolution was observed for VV116 compared with placebo among 1296 patients (HR 1·17, 95% CI 1·04-1·33; p=0·0009), consistent with the interim analysis. The incidence of adverse events was similar between groups (242 [35·9%] of 674 patients vs 283 [42·1%] of 673 patients). INTERPRETATION: Among patients with mild-to-moderate COVID-19, VV116 significantly reduced the time to sustained clinical symptom resolution compared with placebo, with no observed safety concerns. FUNDING: Shanghai Vinnerna Biosciences, Shanghai Science and Technology Commission, and the National Key Research and Development Program of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.