Public Health Measures and the Control of COVID-19 in China.

In December 2019, the COVID-19 pandemic quickly spread throughout China and beyond, posing enormous global challenges. With prompt, vigorous, and coordinated control measures, mainland China contained the spread of the epidemic within two months and halted the epidemic in three months. Aggressive containment strategy, hierarchical management, rational reallocation of resources, efficient contact tracing, and voluntary cooperation of Chinese citizens contributed to the rapid and efficient control of the epidemic, thus promoting the rapid recovery of the Chinese economy. This review summarizes China's prevention and control strategies and other public health measures, which may provide a reference for the epidemic control in other countries.

Smoking: a leading factor for the death of chronic respiratory diseases derived from Global Burden of Disease Study 2019.

BACKGROUND: Smoking is believed as one of the major risk factors resulting in a variety of non-communicable diseases, such as lung cancer and chronic respiratory diseases (CRDs). However, the global burden of CRDs attributed to smoking has not been systematically studied, particularly across different temporal and spatial scales. METHODS: We conducted a systematic analysis of the Global Burden of CRDs and related risk factors using data from the Global Burden of Disease Study 2019. Incidence, death, risk factors, and other parameters such as estimated annual percentage change have been analyzed. We also compared various risk factors across regions, countries, and genders. RESULTS: Globally, the incidence of CRDs and deaths cases have increased in the last 30 years, while the corresponding age-standardized incidence rate (ASIR) and death rate (ASDR) have declined. Smoking was the leading risk factor for the death of CRDs all over the world. However, in low and low-middle Socio-demographic Index (SDI) areas, particulate matter pollution was the main risk factor leading to death from CRDs, while smoking was ranked first among the major risk factors in areas with middle, middle-high, or high SDI. Globally, gender differences in morbidity and mortality from CRDs were observed. Males had slightly more cases and ASIR of chronic respiratory diseases than females over the last 30 years. However, the mortality cases and ASDR in males were significantly higher than that of females. Furthermore, the ASDR of all major risk factors, specially smoking, was higher in men than in women. CONCLUSIONS: CRDs were still major threats human health. The current study highlights the dominating roles of smoking for death risks resulting from CRDs, followed by PM pollution. Therefore, tobacco control and improving air quality are key to reducing deaths from CRDs.

Clinical utility of heparin-binding protein as an acute-phase inflammatory marker in interstitial lung disease.

The role of heparin-binding protein (HBP) as an acute inflammatory marker in acute exacerbations of interstitial lung disease (AE-ILD) and some stable ILD patients is not well-established. The significance of increasing HBP during an AE-ILD is examined and the first attempt to incorporate HBP into the ILD evaluation system is made. Then, the benefit of HBP in AE-ILD was investigated. ILD patients (n = 108) were divided into subgroups based on the phase and severity of the disease. Linear trends of HBP across subgroups were observed, and correlations with common inflammatory markers were examined. Further, the HBP detection was adopted between serum and bronchoalveolar lavage fluid (BALF). Imaging and pathology changes were evaluated using various scoring criteria and compared to HBP. The relationship between HBP with ventilation, fibrosis progression, and changes in arterial oxygen levels and inflammatory markers were investigated to understand the mechanistic pathways. HBP was significantly higher in patients with AE-ILD at the early stage, compared to patients with ILD at the stable phase and its increase was both found in the serum and BALF. With the remission of the disease, there was a linear trend of progressive decline. HBP identified ILD patients who had co-infections. HBP levels increased earlier than CRP, PCT, and SAA. HBP was associated with pulmonary levels of ventilation and lesions by radiology examination, and its levels were significantly worse in AE-ILD patients. However, HBP did not show a correlation to the pathology quantitative evaluation. In conclusion, HBP could potentially evaluate the progression and prognosis of AE-ILD. Because ILD patients are susceptible to infection, and since HBP can identify co-infection, this marker would be of great clinical importance. HBP is possibly predictive of acute exacerbation.

Integrative omics analysis identifies biomarkers of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by chronic progressive pulmonary fibrosis and a poor prognosis. Genetic studies, including transcriptomic and proteomics, have provided new insight into revealing mechanisms of IPF. Herein we provided a novel strategy to identify biomarkers by integrative analysis of transcriptomic and proteomic profiles of IPF patients. We examined the landscape of IPF patients' gene expression in the transcription and translation phases and investigated the expression and functions of two new potential biomarkers. Differentially expressed (DE) mRNAs were mainly enriched in pathways associated with immune system activities and inflammatory responses, while DE proteins are related to extracellular matrix production and wound repair. The upregulated genes in both phases are associated with wound repair and cell differentiation, while the downregulated genes in both phases are associated with reduced immune activities and the damage of the alveolar tissues. On this basis, we identified thirteen potential marker genes. Among them, we validated the expression changes of butyrophilin-like 9 (BTNL9) and plasmolipin (PLLP) and investigated their functional pathways in the IPF mechanism. Both genes are downregulated in the tissues of IPF patients and Bleomycin-induced mice, and co-expression analysis indicates that they have a protective effect by inhibiting extracellular matrix production and promoting wound repair in alveolar epithelial cells.

The Prognostic Value of Krebs von den Lungen-6 and Surfactant Protein-A Levels in the Patients with Interstitial Lung Disease.

BACKGROUND AND OBJECTIVES: The highly variable clinical course of interstitial lung disease (ILD) makes it difficult to predict patient prognosis. Serum surfactant protein-A (SP-A) and Krebs von den Lungen-6 (KL-6) are known prognostic biomarkers. However, the clinical or pathophysiological differences in patients with these biomarkers have not been well evaluated. We investigated the clinical and pathophysiological differences through the comparison of SP-A and KL-6 levels before and after treatment. METHODS: This study included retrospective data from 91 patients who were treated for ILD between August 2015 and September 2019. Serum SP-A and KL-6 levels were measured before and after treatment. The patients were followed up for 3 months. RESULTS: Changes in the serum biomarkers (Delta SP-A and Delta KL-6) were found to be significantly correlated (rs = 0.523, P < 0.001); Delta SP-A and Delta KL-6 were inversely correlated with changes in pulmonary function (% predicted values of diffusing capacity for carbon monoxide [DLCO], forced vital capacity [FVC], and forced expiratory volume in 1 s [FEV1]). Patients were divided into four groups based on their Delta SP-A and Delta KL-6 levels in a cluster analysis (G1, G2, G3, and G4). Both SP-A and KL-6 were elevated in the G1 group, with all the patients enrolled classified as progressive or unchanged, and 86.4% of patients showed improved disease activity in the G4 group, where both SP-A and KL-6 levels were reduced. In the G2 group, only SP-A levels decreased post-treatment, indicating an improvement in respiratory function; the patients were not at the end stage of the disease. Only the SP-A levels increased in the G3 group with immunosuppressive treatment. CONCLUSIONS: Reduced serum SP-A and/or KL-6 levels are associated with improved lung function in patients with ILD. Some patients only showed a decrease in SP-A levels could prognosis an improvement in respiratory function. When only SP-A is increased, it may imply that the patients are at an early stage of disease progression. As a result, for proper disease monitoring, measuring both markers is important.

Factors Affecting the Antibody Immunogenicity of Vaccines against SARS-CoV-2: A Focused Review.

Vaccines are a crucial part of the global anti-pandemic effort against COVID-19. The effects of vaccines, as well as their common influencing factors, are the most important issues that we should focus on at this time. To this end, we review statistics on immunogenicity after vaccination, using neutralizing antibodies as the main reference index. Age, infection history, and virus variants are compared, and vaccination program recommendations are made accordingly. Suggestions are made to address concerns raised by the vaccines' shortened development cycle, as well as the emergence of immunity escape of viral variants. Finally, a brief description and future prospects are provided based on the principle of the ADE effect and previous experience with similar viruses.

Dietary Structure and Nutritional Status of Chinese Beekeepers: Demographic Health Survey.

BACKGROUND: Beekeeping and honey gathering are traditional forms of agricultural farming in China. However, only few studies have focused on the nutritional status and health level of this special occupational group. OBJECTIVE: By comparing the health status of apiculturists (beekeepers) and vegetable farmers in plain areas of Hubei Province, and analyzing the influence of dietary structure and intake on their nutritional level, this paper provides a scientific theoretical basis for the further development of health education and disease prevention for beekeepers. METHODS: From February to April 2016, 191/236 beekeepers (80.9% of the total beekeepers) with large-scale breeding (300-500 colonies) and 182 vegetable farmers in the same area were sampled by the cluster sampling method. Their nutrient composition was analyzed using a human body composition analyzer, dietary structure information was collected using the dietary frequency query method, and cognitive function was investigated. In addition, blood samples of both groups were collected. RESULTS: A total of 362 valid questionnaires (beekeepers/vegetable farmers: 185/177) were collected, with an effective response rate of 97.1% (362/373). Both beekeepers and vegetable farmers were overweight, and the beekeepers' grip strength was much stronger than that of the vegetable farmers' regardless of gender. The dietary structure of beekeepers is very unique: 29.7% (55/185) of beekeepers indicated consuming royal jelly regularly for more than 10 years. Their main foods are grain, cereals, and fresh vegetables; 68.1% (126/185) of the beekeepers never drank milk and other dairy products, and their overall nutrient intake is unbalanced. The average intake of cellulose in this group was also significantly higher than that in the epidemiological survey in the same sex and age group. The intake of vitamin A and selenium in the beekeepers group was significantly higher than that in the vegetable-farmers group (all P<.001). The blood indices of creatinine (P=.03) and blood copper (P<.001) in the beekeepers group were significantly higher than those in the vegetable-farmers group, and the total protein, albumin, calcium, sodium, potassium, phosphorus, folic acid, and vitamin B12 in the beekeepers group were significantly lower than those in the vegetable-farmers group (P<.03 for potassium and P<.001 for others). The total Mini-Mental State Examination (MMSE) score of the beekeepers group was 28.1, significantly higher (P=.006) than that of the vegetable-farmers group (23.3). CONCLUSIONS: The beekeepers in this area have their special dietary structure, body nutrient level, and disease characteristics. The cognitive level of the beekeepers who regularly consume royal jelly is significantly higher than that of their peers. The chronic diseases of this special occupational group are closely related to their lifestyle and nutritional status, so more attention and in-depth studies are needed to improve the quality of life of this population.

The Infection Rate of COVID-19 in Wuhan, China: Combined Analysis of Population Samples.

BACKGROUND: The coronavirus disease (COVID-19) pandemic began in Wuhan, China, in December 2019. Wuhan had a much higher mortality rate than the rest of China. However, a large number of asymptomatic infections in Wuhan may have never been diagnosed, contributing to an overestimated mortality rate. OBJECTIVE: This study aims to obtain an accurate estimate of infections in Wuhan using internet data. METHODS: In this study, we performed a combined analysis of the infection rate among evacuated foreign citizens to estimate the infection rate in Wuhan in late January and early February. RESULTS: Based on our analysis, the combined infection rate of the foreign evacuees was 0.013 (95% CI 0.008-0.022). Therefore, we estimate the number of infected people in Wuhan to be 143,000 (range 88,000-242,000), which is significantly higher than previous estimates. Our study indicates that a large number of infections in Wuhan were not diagnosed, which has resulted in an overestimated case fatality rate. CONCLUSIONS: Increased awareness of the original infection rate of Wuhan is critical for proper public health measures at all levels, as well as to eliminate panic caused by overestimated mortality rates that may bias health policy actions by the authorities.

A data-driven, knowledge-based approach to biomarker discovery: application to circulating microRNA markers of colorectal cancer prognosis.

Recent advances in high-throughput technologies have provided an unprecedented opportunity to identify molecular markers of disease processes. This plethora of complex-omics data has simultaneously complicated the problem of extracting meaningful molecular signatures and opened up new opportunities for more sophisticated integrative and holistic approaches. In this era, effective integration of data-driven and knowledge-based approaches for biomarker identification has been recognised as key to improving the identification of high-performance biomarkers, and necessary for translational applications. Here, we have evaluated the role of circulating microRNA as a means of predicting the prognosis of patients with colorectal cancer, which is the second leading cause of cancer-related death worldwide. We have developed a multi-objective optimisation method that effectively integrates a data-driven approach with the knowledge obtained from the microRNA-mediated regulatory network to identify robust plasma microRNA signatures which are reliable in terms of predictive power as well as functional relevance. The proposed multi-objective framework has the capacity to adjust for conflicting biomarker objectives and to incorporate heterogeneous information facilitating systems approaches to biomarker discovery. We have found a prognostic signature of colorectal cancer comprising 11 circulating microRNAs. The identified signature predicts the patients' survival outcome and targets pathways underlying colorectal cancer progression. The altered expression of the identified microRNAs was confirmed in an independent public data set of plasma samples of patients in early stage vs advanced colorectal cancer. Furthermore, the generality of the proposed method was demonstrated across three publicly available miRNA data sets associated with biomarker studies in other diseases.

Intratumoral heterogeneity identified at the epigenetic, genetic and transcriptional level in glioblastoma.

Heterogeneity is a hallmark of glioblastoma with intratumoral heterogeneity contributing to variability in responses and resistance to standard treatments. Promoter methylation status of the DNA repair enzyme O(6)-methylguanine DNA methyltransferase (MGMT) is the most important clinical biomarker in glioblastoma, predicting for therapeutic response. However, it does not always correlate with response. This may be due to intratumoral heterogeneity, with a single biopsy unlikely to represent the entire lesion. Aberrations in other DNA repair mechanisms may also contribute. This study investigated intratumoral heterogeneity in multiple glioblastoma tumors with a particular focus on the DNA repair pathways. Transcriptional intratumoral heterogeneity was identified in 40% of cases with variability in MGMT methylation status found in 14% of cases. As well as identifying intratumoral heterogeneity at the transcriptional and epigenetic levels, targeted next generation sequencing identified between 1 and 37 unique sequence variants per specimen. In-silico tools were then able to identify deleterious variants in both the base excision repair and the mismatch repair pathways that may contribute to therapeutic response. As these pathways have roles in temozolomide response, these findings may confound patient management and highlight the importance of assessing multiple tumor biopsies.