Blended BA.5 infection within 8 days after a boosted bivalent mRNA vaccination strengthens and lengthens the host immunity.

The impact of SARS-CoV-2 infection shortly after vaccination on vaccine-induced immunity is unknown, which is also one of the concerns for some vaccinees during the pandemic. Here, based on a cohort of individuals who encountered BA.5 infection within 8 days after receiving the fourth dose of a bivalent mRNA vaccine, preceded by three doses of inactivated vaccines, we show that booster mRNA vaccination provided 48% protection efficacy against symptomatic infections. At Day 7 postvaccination, the level of neutralizing antibodies (Nabs) against WT and BA.5 strains in the uninfected group trended higher than those in the symptomatic infection group. Moreover, there were greater variations in Nabs levels and a significant decrease in virus-specific CD4+ T cell response observed in the symptomatic infection group. However, symptomatic BA.5 infection significantly increased Nab levels against XBB.1.9.1 and BA.5 (symptomatic > asymptomatic > uninfected group) at Day 10 and resulted in a more gradual decrease in Nabs against BA.5 compared to the uninfected group at Day 90. Our data suggest that BA.5 infection might hinder the early generation of Nabs and the recall of the CD4+ T cell response but strengthens the Nab and virus-specific T cell response in the later phase. Our data confirmed that infection can enhance host immunity regardless of the short interval between vaccination and infection and alleviate concerns about infections shortly after vaccination, which provides valuable guidance for developing future vaccine administration strategies.

Association between computed tomography-quantified respiratory muscles and chronic obstructive pulmonary disease: a retrospective study.

BACKGROUND: This study examined the association between chest muscles and chronic obstructive pulmonary disease (COPD) and the relationship between chest muscle areas and acute exacerbations of COPD (AECOPD). METHODS: There were 168 subjects in the non-COPD group and 101 patients in the COPD group. The respiratory and accessory respiratory muscle areas were obtained using 3D Slicer software to analysis the imaging of  computed tomography (CT). Univariate and multivariate Poisson regressions were used to analyze the number of AECOPD cases during the preceding year. The cutoff value was obtained using a receiver operating characteristic (ROC) curve. RESULTS: We scanned 6342 subjects records, 269 of which were included in this study. We then measured the following muscle areas (non-COPD group vs. COPD group): pectoralis major (19.06 ± 5.36 cm2 vs. 13.25 ± 3.71 cm2, P < 0.001), pectoralis minor (6.81 ± 2.03 cm2 vs. 5.95 ± 1.81 cm2, P = 0.001), diaphragmatic dome (1.39 ± 0.97 cm2 vs. 0.85 ± 0.72 cm2, P = 0.011), musculus serratus anterior (28.03 ± 14.95 cm2 vs.16.76 ± 12.69 cm2, P < 0.001), intercostal muscle (12.36 ± 6.64 cm2 vs. 7.15 ± 5.6 cm2, P < 0.001), pectoralis subcutaneous fat (25.91 ± 13.23 cm2 vs. 18.79 ± 10.81 cm2, P < 0.001), paravertebral muscle (14.8 ± 4.35 cm2 vs. 13.33 ± 4.27 cm2, P = 0.007), and paravertebral subcutaneous fat (12.57 ± 5.09 cm2 vs. 10.14 ± 6.94 cm2, P = 0.001). The areas under the ROC curve for the pectoralis major, intercostal, and the musculus serratus anterior muscle areas were 81.56%, 73.28%, and 71.56%, respectively. Pectoralis major area was negatively associated with the number of AECOPD during the preceding year after adjustment (relative risk, 0.936; 95% confidence interval, 0.879-0.996; P = 0.037). CONCLUSION: The pectoralis major muscle area was negative associated with COPD. Moreover, there was a negative correlation between the number of AECOPD during the preceding year and the pectoralis major area.

Dynamic immune landscape in vaccinated-BA.5-XBB.1.9.1 reinfections revealed a 5-month protection-duration against XBB infection and a shift in immune imprinting.

BACKGROUND: The impact of previous vaccination on protective immunity, duration, and immune imprinting in the context of BA.5-XBB.1.9.1 reinfection remains unknown. METHODS: Based on a 2-year longitudinal cohort from vaccination, BA.5 infection and XBB reinfection, several immune effectors, including neutralizing antibodies (Nabs), antibody-dependent cellular cytotoxicity (ADCC), virus-specific T cell immunity were measured to investigate the impact of previous vaccination on host immunity induced by BA.5 breakthrough infection and BA.5-XBB.1.9.1 reinfection. FINDINGS: In absence of BA.5 Nabs, plasma collected 3 months after receiving three doses of inactivated vaccine (I-I-I) showed high ADCC that protected hACE2-K18 mice from fatality and significantly reduced viral load in the lungs and brain upon BA.5 challenge, compared to plasma collected 12 months after I-I-I. Nabs against XBB.1.9.1 induced by BA.5 breakthrough infection were low at day 14 and decreased to a GMT of 10 at 4 months and 28% (9/32) had GMT ≤4, among whom 67% (6/9) were reinfected with XBB.1.9.1 within 1 month. However, 63% (20/32) were not reinfected with XBB.1.9.1 at 5 months post BA.5 infection. Interestingly, XBB.1.9.1 reinfection increased Nabs against XBB.1.9.1 by 24.5-fold at 14 days post-reinfection, which was much higher than that against BA.5 (7.3-fold) and WT (4.5-fold), indicating an immune imprinting shifting from WT to XBB antigenic side. INTERPRETATION: Overall, I-I-I can provide protection against BA.5 infection and elicit rapid immune response upon BA.5 infection. Furthermore, BA.5 breakthrough infection effectively protects against XBB.1.9.1 lasting more than 5 months, and XBB.1.9.1 reinfection results in immune imprinting shifting from WT antigen induced by previous vaccination to the new XBB.1.9.1 antigen. These findings strongly suggest that future vaccines should target variant strain antigens, replacing prototype strain antigens. FUNDING: This study was supported by R&D Program of Guangzhou National Laboratory (SRPG23-005), National Key Research and Development Program of China (2022YFC2604104, 2019YFC0810900), S&T Program of Guangzhou Laboratory (SRPG22-006), and National Natural Science Foundation of China (81971485, 82271801, 81970038), Emergency Key Program of Guangzhou Laboratory (EKPG21-30-3), Zhongnanshan Medical Foundation of Guangdong Province (ZNSA-2020013), and State Key Laboratory of Respiratory Disease (J19112006202304).

Comparison of Azvudine and Nirmatrelvir/Ritonavir and Combined Use in Patients with COVID-19.

Purpose: To compare the effectiveness of azvudine and nirmatrelvir/ritonavir for the treatment of coronavirus disease (COVID-19). Patients and Methods: We conducted a retrospective analysis of data from 576 patients with COVID-19, comprising 195 patients without antiviral therapy, 226 patients treated with azvudine, 114 patients treated with nirmatrelvir/ritonavir, and 41 patients were treated with azvudine and nirmatrelvir/ritonavir concurrently. We compared their symptoms, mortality rates, and the length and cost of hospitalization. Results: The incidence of symptoms was similar in patients treated with azvudine and in those treated with nirmatrelvir/ritonavir. However, among patients experiencing weakness, the duration of weakness was significantly shorter in the azvudine group than in the nirmatrelvir/ritonavir group (P=0.029). Mortality did not differ significantly between the azvudine group and the nirmatrelvir/ritonavir group (18.14% vs.10.53%, P=0.068). Among "severe patients", the mortality rate was markedly lower in patients treated with nirmatrelvir/ritonavir than in patients treated with azvudine (16.92% vs.32.17%, P=0.026). In patients with hepatic insufficiency, those treated with nirmatrelvir/ritonavir had substantially lower mortality than those treated with azvudine (15.09% vs.34.25%, P=0.016). In addition, patients treated with nirmatrelvir/ritonavir had longer hospital stays (P=0.002) and higher hospital costs (P<0.001) than those receiving azvudine. Compared with patients treated with nirmatrelvir/ritonavir or azvudine alone, patients taking nirmatrelvir/ritonavir and azvudine concurrently had no significant improvement in survival (P>0.05), length of stay (P>0.05), or hospital costs (P>0.05). Conclusion: Azvudine is recommended for patients with non-severe COVID-19 with weakness. Nirmatrelvir/ritonavir is recommended for patients with severe COVID-19, to reduce mortality, and it could be the best choice for patients with hepatic insufficiency. The concurrent use of nirmatrelvir/ritonavir and azvudine in patients with COVID-19 could be not recommended.

GRIK3 deficiency promotes non-small cell lung cancer progression by the regulation of the UBE2C/CDK1/Wnt signaling pathway.

Glutamate ionotropic receptor kainate type subunit 3 (GRIK3) is a predominant excitatory neurotransmitter receptor in the mammalian brain. While it is known that GRIK3 is involved in normal neurophysiologic processes, its biological functions in tumor progression are still poorly understood due to limited investigation. In this study, we reported for the first time that GRIK3 expression was downregulated in non-small cell lung cancer (NSCLC) tissues as compared to paracarcinoma tissues. Additionally, we observed that GRIK3 expression was strongly correlated with the prognosis of NSCLC patients. We also noted that GRIK3 suppressed the cell proliferation and migration capability of NSCLC cells, thereby inhibiting xenografts growth and metastasis. Mechanistically, GRIK3 deficiency increased the expression of ubiquitin-conjugating enzyme E2 C (UBE2C) and cyclin-dependent kinase 1 (CDK1), which resulted in the activation of the Wnt signaling pathway and enhanced NSCLC progression. Our findings suggest that GRIK3 plays a role in regulating NSCLC progression and that its expression may serve as an independent prognostic indicator for NSCLC patients.

Characteristics of patients with SARS-COV-2 PCR re-positivity after recovering from COVID-19.

The purpose of this study was to analyse the clinical characteristics of patients with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) PCR re-positivity after recovering from coronavirus disease 2019 (COVID-19). Patients (n = 1391) from Guangzhou, China, who had recovered from COVID-19 were recruited between 7 September 2021 and 11 March 2022. Data on epidemiology, symptoms, laboratory test results and treatment were analysed. In this study, 42.7% of recovered patients had re-positive result. Most re-positive patients were asymptomatic, did not have severe comorbidities, and were not contagious. The re-positivity rate was 39%, 46%, 11% and 25% in patients who had received inactivated, mRNA, adenovirus vector and recombinant subunit vaccines, respectively. Seven independent risk factors for testing re-positive were identified, and a predictive model was constructed using these variables. The predictors of re-positivity were COVID-19 vaccination status, previous SARs-CoV-12 infection prior to the most recent episode, renal function, SARS-CoV-2 IgG and IgM antibody levels and white blood cell count. The predictive model could benefit the control of the spread of COVID-19.

Clinical Epidemiology, Treatment, and Prognostic Factors of Hospital-Acquired Pneumonia Caused by the Extensively Drug-Resistant Acinetobacter Baumannii.

BACKGROUND: Extensively drug-resistant Acinetobacter baumannii (XDRAB) can acquire drug resistance genes, which are rapidly cloned and transmitted, leading to worldwide spread and posing significant treatment challenges. This study aimed to clarify effective treatment methods during XDRAB infection and factors affecting patient prognosis. METHODS: Clinical features, treatment, and prognosis of 65 patients with hospital-acquired XDRAB pneumonia clinically diagnosed at Guangzhou First People's Hospital between January 2019 and December 2020 were retrospectively analyzed. RESULTS: Of 65 subjects, only 37 survived. There was no significant difference in anti-A. baumannii activity according to type or combination of antibiotics administered between patients that survived and those that died (p > 0.05). The use of antibacterial drugs during infection did not effectively improve clinical outcomes. Advanced age, multiple organ failure, and disease severity were significantly negatively correlated while effective airway management was positively associated with bacterial clearance (p < 0.05). In multivariate analysis, age and APACHE score were independent risk factors affecting prognosis. Tracheotomy during infection was a protective factor contributing to survival (p < 0.05). Advanced age and disease severity independently affected patient prognosis, while use and type of antibacterial treatment did not substantially affect the prognosis. CONCLUSIONS: Advanced age and severe disease are independent risk factors that affect patient prognosis. Timely and effective airway management is key to improving the prognosis of patients with hospital-acquired XDRAB infection.

SARS-CoV-2 vaccination-infection pattern imprints and diversifies T cell differentiation and neutralizing response against Omicron subvariants.

The effects of different SARS-CoV-2 vaccinations and variant infection histories on imprinting population immunity and their influence on emerging escape mutants remain unclear. We found that Omicron (BA.1) breakthrough infection, regardless of vaccination with two-dose mRNA vaccines (M-M-o) or two-dose inactivated vaccines (I-I-o), led to higher neutralizing antibody levels against different variants and stronger T-cell responses than Delta breakthrough infection after two-dose inactivated vaccine vaccination (I-I-δ). Furthermore, different vaccination-infection patterns imprinted virus-specific T-cell differentiation; M-M-ο showed higher S/M/N/E-specific CD4+ T cells and less portion of virus-specific CD45RA+CD27-CD8+ T cells by ex vivo assay. Breakthrough infection groups showed higher proliferation and multi-function capacity by in vitro assay than three-dose inactivated vaccine inoculated group (I-I-I). Thus, under wide vaccination coverage, the higher immunogenicity with the Omicron variant may have helped to eliminate the population of Delta variant. Overall, our data contribute to our understanding of immune imprinting in different sub-populations and may guide future vaccination programs.

Heterologous booster with inhaled adenovirus vector COVID-19 vaccine generated more neutralizing antibodies against different SARS-CoV-2 variants.

The rapid widespread Omicron subvariant BA.5 of SARS-CoV-2 has become a potential imminent pandemic threat, but available vaccines lack high efficacy against this subvariant. Thus, it is urgent to find highly protective vaccination strategies within available SARS-CoV-2 vaccines. Here, by using a SARS-CoV-2 pseudovirus neutralization assay, we demonstrated that the aerosol inhalation of adenoviral vector COVID-19 vaccine after two dose of inactivated vaccine (I-I-Ad5) led to higher levels of neutralizing antibodies against D614G strain (2041.00[95% CI, 1243.00-3351.00] vs 249.00[149.10-415.70]), Omicron BA.2 (467.10[231.00-944.40] vs 72.21[39.31-132.70]), BA.2.12.1(348.5[180.3-673.4] vs 53.17[31.29-90.37]), BA.2.13 (410.40[190.70-883.3] vs 48.48[27.87-84.32]), and BA.5 (442.40 vs 56.08[35.14-89.51]) than three inactivated vaccine doses (I-I-I). Additionally, the level of neutralizing antibodies against BA.5 induced by I-I-Ad5 was 2.41-fold higher than those boosted by a third dose of RBD subunit vaccine (I-I-S) (p = 0.1308). The conventional virus neutralizing assay confirmed that I-I-Ad5 induced higher titre of neutralizing antibodies than I-I-I (116.80[84.51-161.5] vs 4.40[4.00-4.83]). In addition, I-I-Ad5 induced higher, but later, anti-RBD IgG and IgA in plasma than I-I-I. Our study verified that mucosal immunization with aerosol inhalation of adenoviral vector COVID-19 vaccine may be an effective strategy to control the probable wave of BA.5 pandemic in addition to two inactivated vaccines.

A novel angiographic classification of pseudoaneurysms of the pulmonary chronic inflammatory cavity based on selective angiograms and therapeutic implications.

Background: Hemoptysis is a common clinical symptom. In the chronic tuberculosis cavity and chronic necrotizing pneumonia cavity, pseudoaneurysms (Pas) easily form and are prone to massive hemoptysis and repeated hemoptysis and can even endanger patient's life. However, it remains to be further analyzed whether Pas of the pulmonary chronic inflammatory cavity selectively affect the peripheral pulmonary branches. This study is based on selective angiography to classify peripheral pulmonary arterial Pas (PAPs) of the pulmonary chronic inflammatory cavity and to determine treatment options for PAPs, thereby guiding individualized clinical treatment. Methods: Angiographic data of 392 noncancer patients undergoing hemoptysis were retrospectively analyzed. All of the patients underwent pulmonary and selective pulmonary angiography and bronchial and nonbronchial systemic collateral arterial angiography. A total of 9 patients had Pas of the pulmonary chronic inflammatory cavity, and a pseudoaneurysm systemic artery collateral (Pasac), inflow and outflow sections of the parent vessels, and direction of blood flow in the parent vessels were clearly observed with digital subtraction angiography (DSA) and/or C-arm cone-beam flat-panel detector computed tomography angiography (CBCTA). Patients with underlying disease had pulmonary tuberculosis (n=8) or lung abscess (n=1). The angiographic types of Pas were analyzed. Results: Eight patients with chronic pulmonary tuberculosis and 1 patient with a necrotizing pneumonia cavity in the convalescent period were included in the study. Pas of the pulmonary chronic inflammatory cavity presented the following types: (I) pulmonary artery pseudoaneurysm (PAPa) (n=2 cases); (II) body arterial Pa (n=3 cases); and (III) systemic-pulmonary anastomosis Pa. Each type could be divided into two subtypes (n=4 cases). In nine cases, embolization and hemostasis were technically and clinically successful. Conclusions: Pas of the pulmonary chronic inflammatory cavity are diverse (especially in cases of pulmonary tuberculosis). Angiographic typing plays a guiding role in the selection of an embolization strategy.

A nomogram based on A-to-I RNA editing predicting overall survival of patients with lung squamous carcinoma.

BACKGROUND: Adenosine-to-inosine RNA editing (ATIRE) is characterized as non-mutational epigenetic reprogramming hallmark of cancer, while little is known about its predictive role in cancer survival. METHODS: To explore survival-related ATIRE events in lung squamous cell carcinoma (LUSC), ATIRE profile, gene expression data, and corresponding clinical information of LUSC patients were downloaded from the TCGA database. Patients were randomly divided into a training (n = 134) and validation cohort (n = 94). Cox proportional hazards regression followed by least absolute shrinkage and selection operator algorithm were performed to identify survival-related ATIRE sites and to generate ATIRE risk score. Then a nomogram was constructed to predict overall survival (OS) of LUSC patients. The correlation of ATIRE level and host gene expression and ATIREs' effect on transcriptome expression were analyzed. RESULTS: Seven ATIRE sites that were TMEM120B chr12:122215052A > I, HMOX2 chr16:4533713A > I, CALCOCO2 chr17:46941503A > I, LONP2 chr16:48388244A > I, ZNF440 chr19:11945758A > I, CLCC1 chr1:109474650A > I, and CHMP3 chr2:86754288A > I were identified to generate the risk score, of which high levers were significantly associated with worse OS and progression-free survival in both the training and validation sets. High risk-score was also associated with advanced T stages and worse clinical stages. The nomogram performed well in predicting OS probability of LUSC. Moreover, the editing of ATIRE sites exerted a significant association with expression of host genes and affected several cancer-related pathways. CONCLUSIONS: This is the first comprehensive study to analyze the role of ATIRE events in predicting LUSC survival. The AITRE-based model might serve as a novel tool for LUSC survival prediction.

Genomic features of Chinese small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) is an aggressive disease with poor survival. Although molecular and clinical characteristics have been established for SCLC in western patients, limited investigation has been performed for Chinese SCLC patients. OBJECTIVE: In this study, we investigated the genomic features of Chinese SCLC patients. METHODS: A total of 75 SCLC patients were enrolled. Genomic alterations in 618 selected genes were analyzed by targeted next-generation sequencing. RESULTS: Here, we showed that TP53 (77.30%) and RB1 (30.70%) were the most prevalent genes alterations, followed by KMT2D, ALK, LRP1B, EGFR, NOTCH3, AR, CREBBP, ROS1, and BRCA2. And the most common genetic alterations were enriched in the cell cycle signaling pathway (84.00%) of Chinese SCLC patients. DNA damage repair (DDR) pathway analysis showed that the most frequently enriched DDR pathways were fanconi anaemia (FA, 29.41%) and homology recombination (HR, 21.57%). Notably, 9.33% SCLC patients in our cohort had pathogenic or likely pathogenic germline gene variants. Compared with the U Cologne cohort, a higher prevalence in EGFR, AR, BRCA2, TSC1, ATXN3, MET, MSH2, ERBB3 and FOXA1 were found in our cohort; while compared to the data from the Johns Hopkins cohort, a higher mutated frequency in TP53, KMT2D, ALK, and EGFR were found in our cohort. Moreover, a significant association was found between high tumor mutation burden (TMB) and mutations involved in TP53, CREBBP, EPHA3, KMT2D, ALK and RB1. Approximately 33.33% of patients with SCLC harbored at least one actionable alteration annotated by OncoKB, of which one patient had alterations of level 1; seventeen patients had level 3; fifteen patients possessed level 4. CONCLUSION: Our data might provide an insightful meaning in targeted therapy for Chinese SCLC patients.

Genomic correlates of programmed cell death ligand 1 (PD-L1) expression in Chinese lung adenocarcinoma patients.

BACKGROUND: Although PD-L1 expression is a crucial predictive biomarker for immunotherapy, it can be influenced by many factors. METHODS: A total of 248 Chinese patients with lung adenocarcinoma was retrospectively identified. Data for clinical features, gene alternations, signaling pathways and immune signatures was analyzed among negative expression group (TPS < 1%, n = 124), intermediate expression group (1% ≤ TPS < 50%, n = 93), and high expression group (TPS ≥ 50%, n = 38). Clinical outcomes among different expression groups were also evaluated from public database. RESULTS: Firstly, high tumor mutation burden was significantly associated with high PD-L1 expression in these Chinese patients with lung adenocarcinoma. In addition, gene alternations including TP53, PRKDC, KMT2D, TET1 and SETD2 apparently occurred in high PD-L1 expression group. Moreover, pathway analysis showed that mutations involving in DDR pathway, TP53 pathway, cell-cycle pathway and NOTCH pathway were obviously varied among three PD-L1 expression groups. Besides, most of patients in high PD-L1 expression group from TCGA database were determined as high-grade immune subtypes (C2-C4), showing significant higher proportions of IFN-gamma, CD8+ T-cells, NK cells, NK CD56 dim cells, Th1 cells, Th2 cells (P < 0.0001). Moreover, SETD2 mutation slightly correlated with overall survival from MSKCC cohort (HR 1.92 [95%CI 0.90-4.10], P = 0.085), and the percentage of IFN-gamma was significantly higher in SETD2 mutant group than in wild-type group (P < 0.01). CONCLUSIONS: This study illustrated in-depth genomic correlates of PD-L1 expression in Chinese lung adenocarcinoma patients and relevant immune signatures from public database, which might interpret more potential molecular mechanisms for immunotherapy in NSCLC.

Heterologous boosting with third dose of coronavirus disease recombinant subunit vaccine increases neutralizing antibodies and T cell immunity against different severe acute respiratory syndrome coronavirus 2 variants.

Waned vaccine-induced immunity and emerging severe acute respiratory syndrome coronavirus 2 variants with potential for immune escape pose a major threat to the coronavirus disease (COVID-19) pandemic. Here, we showed that humoral immunity components, including anti-S + N, anti-RBD IgG, and neutralizing antibodies (NAbs), gradually waned and decreased the neutralizing capacity against emerging Omicron variants at 3 and 6 months after two inactivated COVID-19 vaccinations. We evaluated two boosting strategies with either a third dose of inactivated vaccine (homologous, I-I-I) or a recombinant subunit vaccine (heterologous, I-I-S). Both strategies induced the production of high levels of NAbs with a broad neutralizing capacity and longer retention. Interestingly, I-I-S induced 3.5-fold to 6.8-fold higher NAb titres than I-I-I, with a broader neutralizing capacity against six variants of concern, including Omicron. Further immunological analysis revealed that the two immunization strategies differ considerably, not only in the magnitude of total NAbs produced, but also in the composite pattern of NAbs and the population of virus-specific CD4+ T cells produced. Additionally, in some cases, heterologous boosted immunity induced the production of more effective epitopes than natural infection. The level of I-I-S-induced NAbs decreased to 48% and 18% at 1 and 3 months after booster vaccination, respectively. Overall, our data provide important evidence for vaccination strategies based on available vaccines and may help guide future global vaccination plans.

Public Health Measures During the COVID-19 Pandemic Reduce the Spread of Other Respiratory Infectious Diseases.

Background: Public health measures (such as wearing masks, physical distancing, and isolation) have significantly reduced the spread of the coronavirus disease-2019 (COVID-19), but the impact of public health measures on other respiratory infectious diseases is unclear. Objective: To assess the correlation between public health measures and the incidence of respiratory infectious diseases in China during the COVID-19 pandemic. Methods: We collected the data from the National Health and Construction Commission in China on the number of patients with six respiratory infectious diseases (measles, tuberculosis, pertussis, scarlet fever, influenza, and mumps) from 2017 to 2020 and assessed the correlation between public health measures and the incidence of respiratory infectious diseases. Finally, we used the data of the six respiratory infectious diseases in 2021 to verify our results. Results: We found public health measures significantly reduced the incidence of measles (p = 0.002), tuberculosis (p = 0.002), pertussis (p = 0.004), scarlet fever (p = 0.002), influenza (p = 0.034), and mumps (p = 0.002) in 2020, and prevented seasonal peaks. Moreover, the effects of public health measures were most marked during the peak seasons for these infections. Of the six respiratory infectious diseases considered, tuberculosis was least affected by public health measures. Conclusion: Public health measures were very effective in reducing the incidence of respiratory infectious diseases, especially when the respiratory infectious diseases would normally have been at their peak.

Clinical characteristics of Hepatoid adenocarcinoma of the lung: Four case reports and literature review.

PURPOSE: Hepatoid adenocarcinoma of the lung (HAL) is a rare form of lung cancer, which is characterized by its morphologic hepatoid features. The clinical characteristics and prognosis of this rare form of lung cancer remain obscure. METHODS: The clinical courses of four cases of HAL were reported. A literature search was performed up to December 31, 2020, using the electronic databases PubMed and Web of Science. RESULTS: Including the present 4 cases, a total of 42 cases of HAL have been reported in the literature. The median age was 58.5 years old (range, 36-73 years). 36 (85.7%) patients were male. 26 (61.9%) patients had a history of smoking, the median amount of smoking was 40 pack years (range, 8-180). The most common site of the primary tumor was the right upper lobe (22 cases, 52.3%) and the left upper lobe (10 cases, 23.8%). 21 patients (50%) had pretreatment serum AFP levels higher than the upper limit, and 4 patients (9.5%) had normal pretreatment serum AFP levels. Treatment of HAL included surgery, chemotherapy, radiotherapy, tyrosine kinase inhibitors (TKIs), anti-angiogenesis therapy, and anti-PD-1/PD-L1 monoclonal antibody. Overall, the prognosis of HAL was poor, with median overall survival (OS) of 14 months. CONCLUSIONS: HAL is an aggressive tumor, with a poor prognosis and male predominance, which tends to occur in heavy smokers and affects the right upper lobe of the lung.

Lung Features in Individuals with Biomass Smoke Exposure Characterized by CT Scan and Changes in Pulmonary Function.

BACKGROUND AND OBJECTIVE: To determine the effects of BSE (biomass smoke exposure) on pulmonary and non-pulmonary changes in patients with COPD compared with normal individuals. METHODS: Using a cohort, we recruited 16 healthy individuals with BSE (BSE normal), 19 patients with BSE+COPD, 13 healthy individuals with cigarette smoke exposure (CSE normal), 25 patients with CSE+COPD, and 25 healthy controls. Patients with GOLD stage I and II COPD were included. Baseline data (demographic data, BSE or CSE, lung function, and CT findings) and follow-up lung function data were collected. CT parameters of emphysema, pulmonary small vessels, airway remodeling, pectoralis muscles, and erector spinae muscle were measured. RESULTS: Individuals with BSE were mainly women (32/35, 91.43%). Compared with the CSE+COPD group, the BSE+COPD group demonstrated slower lung function decline, increased lower lung emphysema, narrower airway lumen dimensions and increased airway wall thickening in the moderate and small airways (all P<0.05). Compared with healthy controls, the CSE normal and BSE normal groups exhibited significant reductions in pulmonary small vessel area and obvious airway remodeling in small airways (P<0.05). Compared with the BSE normal group, the BSE+COPD group showed significantly more severe emphysema and airway remodeling, as well as reduced left pectoralis major muscle area (all P<0.05). CONCLUSION: Healthy individuals with BSE had reduced pulmonary small vessel area and evidence of airway remodeling; patients with BSE and COPD showed more severe emphysema, airway remodeling, and reductions in pectoralis major muscle area. CLINICAL TRIAL REGISTRATION: ChiCTR-OO-14004264.

Validity of the Handheld Expiratory Flowmeter for COPD Screening in the Primary Care Setting of China.

Purpose: The use of simple and affordable screening tools for chronic obstructive pulmonary disease (COPD) is limited. We aimed to assess the validity of a handheld expiratory flowmeter (Vitalograph Ltd., COPD-6®, Ireland) for COPD screening in Chinese primary care settings. Methods: In our cross-sectional study, subjects were randomly selected in eight primary care settings. Tests with the handheld expiratory flowmeter and the conventional spirometry were sequentially performed on all participants. The correlation between the handheld expiratory flowmeter and the conventional spirometry was determined. Validity was determined by the area under the receiver operator characteristic curve (AUC) of the forced expiratory volume in one second (FEV1)/forced expiratory volume in six seconds (FEV6) that used to detect airway obstruction. The sensitivity, specificity, predictive values, and likelihood ratio were calculated according to different FEV1/FEV6 cut-off points. Results: A total of 229 subjects (15.4%) were diagnosed with airflow limitation by conventional spirometry. FEV1, FEV6, and FEV1/FEV6 measured by the handheld expiratory flowmeter were correlated with FEV1, FVC, and FEV1/FVC measured by the conventional spirometry (r=0.889, 0.835 and 0.647, p<0.001), respectively. AUC of the FEV1/FEV6 to determine airflow obstruction was 0.857 (95% CI: 0.826 to 0.888). No significant difference of AUC was observed between the symptomatic group and the asymptomatic group (AUC=0.869 vs 0.843, P=0.425). A similar phenomenon was found in the AUC of smokers and never-smokers (AUC=0.862 vs 0.840; P=0.515). The cut-off point for FEV1/FEV6 was 0.77 and the corresponding sensitivity and specificity were 71.2% and 89.8%, respectively. Conclusion: The handheld expiratory flowmeter might be used as a screening device for COPD in Chinese primary care settings.

Discovery of a novel linc01125 isoform in serum exosomes as a promising biomarker for NSCLC diagnosis and survival assessment.

A non-invasive method to distinguish potential lung cancer patients would improve lung cancer prevention. We employed the RNA-sequencing analysis to profile serum exosomal long non-coding RNAs (lncRNAs) from non-small cell lung cancer (NSCLC) patients and pneumonia controls, and then determined the diagnostic and prognostic value of a promising lncRNA in four datasets. We identified 90 dysregulated lncRNAs for NSCLC and found the most significant lncRNA was a novel isoform of linc01125. Serum exosomal linc01125 could distinguish NSCLC cases from disease-free and tuberculosis controls, with the area under the curve values as 0.662 [95% confidence interval (CI) = 0.614-0.711] and 0.624 (95% CI = 0.522-0.725), respectively. High expression of exosomal linc01125 was also correlated with an unfavorable overall survival of NSCLC (hazard ratio = 1.48, 95% CI = 1.05-2.08). Clinic treatment decreased serum exosomal linc01125 in NSCLC patients (P = 0.036). Linc01125 functions to inhibit cancer growth and metastasis via acting as a competing endogenous RNA to up-regulate tumor necrosis factor alpha-induced protein 3 (TNFAIP3) expression by sponging miR-19b-3p. Notably, the oncogenic transformation of 16HBE led to decreased linc01125 in cells but increased linc01125 in cell-derived exosomes. The expression of linc01125 in total exosomes was highly correlated with that in tumor-associated exosomes in serum. Moreover, lung cancer cells were capable of releasing linc01125 into exosomes in vitro and in vivo. Our analyses suggest serum exosomal linc01125 as a promising biomarker for non-invasively diagnosing NSCLC and predicting the prognosis of NSCLC.

Identification of Three Circular RNA Cargoes in Serum Exosomes as Diagnostic Biomarkers of Non-Small-Cell Lung Cancer in the Chinese Population.

The recent discovery of circular RNAs (circRNAs) in serum exosomes suggests a novel and potentially useful tool for noninvasive cancer diagnosis. However, there are currently no substantial studies addressing this topic. RNA-sequencing analysis was performed between three pairs of non-small-cell lung cancer (NSCLC) patients and controls. The diagnostic values of exosomal circRNAs were assessed in a training set, validation set 1, and validation set 2. A total of 46 abnormally expressed circRNAs were identified. Among these, circ_0047921, circ_0056285, and circ_0007761 were found to display significant diagnostic validity for NSCLC. In distinguishing NSCLC cases from healthy controls, the panel of aforementioned circRNAs exhibited area under the curve (AUC) values of 0.926 (95% CI, 0.895-0.956) in the training set and 0.919 (95% CI, 0.877-0.962) in validation set 1. Circ_0047921 could distinguish NSCLC cases from chronic obstructive pulmonary disease controls (AUC, 0.890; 95%CI, 0.831-0.948), whereas the circ_0056285 and circ_0007761 combination could distinguish NSCLC cases from tuberculosis controls (AUC, 0.820; 95% CI, 0.739-0.902). For an early NSCLC diagnosis, similar results were observed for these circRNAs in distinguishing early-stage NSCLC cases from healthy controls, chronic obstructive pulmonary disease controls, or tuberculosis controls. Circ_0056285 expression was correlated with clinical stages and lymph node metastasis. The exosomal circRNAs, circ_0047921, circ_0056285, and circ_0007761, are promising biomarkers for NSCLC diagnosis in the Chinese population.