Novel insights from spatial transcriptome analysis in solid tumors.

Since its first application in 2016, spatial transcriptomics has become a rapidly evolving technology in recent years. Spatial transcriptomics enables transcriptomic data to be acquired from intact tissue sections and provides spatial distribution information and remedies the disadvantage of single-cell RNA sequencing (scRNA-seq), whose data lack spatially resolved information. Presently, spatial transcriptomics has been widely applied to various tissue types, especially for the study of tumor heterogeneity. In this review, we provide a summary of the research progress in utilizing spatial transcriptomics to investigate tumor heterogeneity and the microenvironment with a focus on solid tumors. We summarize the research breakthroughs in various fields and perspectives due to the application of spatial transcriptomics, including cell clustering and interaction, cellular metabolism, gene expression, immune cell programs and combination with other techniques. As a combination of multiple transcriptomics, single-cell multiomics shows its superiority and validity in single-cell analysis. We also discuss the application prospect of single-cell multiomics, and we believe that with the progress of data integration from various transcriptomics, a multilayered subcellular landscape will be revealed.

Advances in spatial transcriptomics and related data analysis strategies.

Spatial transcriptomics technologies developed in recent years can provide various information including tissue heterogeneity, which is fundamental in biological and medical research, and have been making significant breakthroughs. Single-cell RNA sequencing (scRNA-seq) cannot provide spatial information, while spatial transcriptomics technologies allow gene expression information to be obtained from intact tissue sections in the original physiological context at a spatial resolution. Various biological insights can be generated into tissue architecture and further the elucidation of the interaction between cells and the microenvironment. Thus, we can gain a general understanding of histogenesis processes and disease pathogenesis, etc. Furthermore, in silico methods involving the widely distributed R and Python packages for data analysis play essential roles in deriving indispensable bioinformation and eliminating technological limitations. In this review, we summarize available technologies of spatial transcriptomics, probe into several applications, discuss the computational strategies and raise future perspectives, highlighting the developmental potential.

Clinical significance of LAG-3 on microvessel density in primary hepatocellular carcinoma.

Aims: We aimed to determine whether lymphocyte activation gene 3 (LAG-3), also known as CD223, is associated with microvessel density (MVD) in primary hepatocellular carcinoma (HCC), as well as their clinical significance in predicting survival. Materials and methods: One hundred and twenty-seven patients were enrolled in the study. Samples were obtained on resection at the Department of Hepatobiliary Surgery of the Qingdao Municipal Hospital from June 2014 to June 2016. Immunohistochemistry was used to determine vessel density and LAG-3 abundance. Statistical analyses were performed to test for correlation of LAG-3 density and other clinicopathological variables with overall survival (OS). Results: High LAG-3 abundance was significantly correlated with increased MVD in primary HCC (P < 0.05). The χ2 test revealed a significant association of LAG-3 with preoperative AFP level, tumor diameter, N stage, and the presence of HBV infection (P < 0.05). Patients with high LAG-3 expression had shorter OS compared to those with low LAG-3 expression (P < 0.05). The Cox proportional hazards model showed that both higher LAG-3 and MVD density, age, the number of tumors, preoperative AFP level, tissue differentiation, Child-Pugh grade, and lymph node metastasis correlated with survival. Conclusions: High expression of LAG-3 is associated with angiogenesis and poor prognosis in HCC patients. With the deepening of research, LAG-3 is likely to become a novel biomarker for clinical diagnosis and prognosis and can even be a therapeutic target of HCC.

A case-case study on the effect of primary and booster immunization with China-produced COVID-19 vaccines on prevention of pneumonia and viral load among vaccinated persons infected by Delta and Omicron variants.

Using a three-prefecture, two-variant COVID-19 outbreak in Henan province in January 2022, we evaluated the associations of primary and booster immunization with China-produced COVID-19 vaccines and COVID-19 pneumonia and SARS-CoV-2 viral load among persons infected by Delta or Omicron variant. We obtained demographic, clinical, vaccination, and multiple Ct values of infections ≥3 years of age. Vaccination status was either primary series ≥180 days prior to infection; primary series <180 days prior to infection, or booster dose recipient. We used logistic regression to determine odds ratios (OR) of Delta and Omicron COVID-19 pneumonia by vaccination status. We analysed minimum Ct values by vaccination status, age, and variant. Of 826 eligible cases, 405 were Delta and 421 were Omicron cases; 48.9% of Delta and 19.0% of Omicron cases had COVID-19 pneumonia. Compared with full primary vaccination ≥180 days before infection, the aOR of pneumonia was 0.48 among those completing primary vaccination <180 days and 0.18 among booster recipients among these Delta infections. Among Omicron infections, the corresponding aOR was 0.34 among those completing primary vaccination <180 days. There were too few (ten) Omicron cases among booster dose recipients to calculate a reliable OR. There were no differences in minimum Ct values by vaccination status among the 356 Delta cases or 70 Omicron cases. COVID-19 pneumonia was less common among Omicron cases than Delta cases. Full primary vaccination reduced pneumonia effectively for 6 months; boosting six months after primary vaccination resulted in further reduction. We recommend accelerating the pace of booster dose administration.

Risk factors for developing severe COVID-19 in China: an analysis of disease surveillance data.

BACKGROUND: COVID-19 has posed an enormous threat to public health around the world. Some severe and critical cases have bad prognoses and high case fatality rates, unraveling risk factors for severe COVID-19 are of significance for predicting and preventing illness progression, and reducing case fatality rates. Our study focused on analyzing characteristics of COVID-19 cases and exploring risk factors for developing severe COVID-19. METHODS: The data for this study was disease surveillance data on symptomatic cases of COVID-19 reported from 30 provinces in China between January 19 and March 9, 2020, which included demographics, dates of symptom onset, clinical manifestations at the time of diagnosis, laboratory findings, radiographic findings, underlying disease history, and exposure history. We grouped mild and moderate cases together as non-severe cases and categorized severe and critical cases together as severe cases. We compared characteristics of severe cases and non-severe cases of COVID-19 and explored risk factors for severity. RESULTS: The total number of cases were 12 647 with age from less than 1 year old to 99 years old. The severe cases were 1662 (13.1%), the median age of severe cases was 57 years [Inter-quartile range(IQR): 46-68] and the median age of non-severe cases was 43 years (IQR: 32-54). The risk factors for severe COVID-19 were being male [adjusted odds ratio (aOR) = 1.3, 95% CI: 1.2-1.5]; fever (aOR = 2.3, 95% CI: 2.0-2.7), cough (aOR = 1.4, 95% CI: 1.2-1.6), fatigue (aOR = 1.3, 95% CI: 1.2-1.5), and chronic kidney disease (aOR = 2.5, 95% CI: 1.4-4.6), hypertension (aOR = 1.5, 95% CI: 1.2-1.8) and diabetes (aOR = 1.96, 95% CI: 1.6-2.4). With the increase of age, risk for the severity was gradually higher [20-39 years (aOR = 3.9, 95% CI: 1.8-8.4), 40-59 years (aOR = 7.6, 95% CI: 3.6-16.3), ≥ 60 years (aOR = 20.4, 95% CI: 9.5-43.7)], and longer time from symtem onset to diagnosis [3-5 days (aOR = 1.4, 95% CI: 1.2-1.7), 6-8 days (aOR = 1.8, 95% CI: 1.5-2.1), ≥ 9 days(aOR = 1.9, 95% CI: 1.6-2.3)]. CONCLUSIONS: Our study showed the risk factors for developing severe COVID-19 with large sample size, which included being male, older age, fever, cough, fatigue, delayed diagnosis, hypertension, diabetes, chronic kidney diasease, early case identification and prompt medical care. Based on these factors, the severity of COVID-19 cases can be predicted. So cases with these risk factors should be paid more attention to prevent severity.

Investigation and analysis of antibody levels of hepatitis A among children before and after implementing the Expanded National Immunization Program in China.

OBJECTIVE: To analyze changes of hepatitis A antibody levels and immunization coverage of HAV vaccine among children before and after implementing the Expanded National Immunization Program in five counties of China, and to provide evidence for developing hepatitis A vaccine immunization strategies. METHODS: 449 children born in 2001, 2005 and 2009 were selected from five counties for an immunization coverage and a sero-prevalence survey of hepatitis A. The chemiluminescence microparticle immunoassays (CMIA) were used to detect hepatitis A IgG antibody and analyzed the factors which influenced the immunization coverage and positive rates. RESULTS: Among 449 subjects of children born in 2001, 2005 and 2009, the immunization coverage were 53.02%, 78.52% and 99.34% (χ2 = 91.285, P < 0.001). The positivity rates of hepatitis A IgG antibody were 61.07%, 81.21%, 95.36% (χ2 = 54.198, P < 0.001), respectively. The immunization coverage and positivity rate significantly increased with the delay of birth year. Children accepting different doses of HA vaccines are significantly different in positive rates of HA antibody, while there are no significant differences of different genders, years of birth, residence types, or types of registered permanent residence in different regions. The positivity rate increased significantly with administration of hepatitis A vaccine and shorter intervals between sample collection and HAV immunization. CONCLUSIONS: After the Expanded National Immunization Program was implemented, hepatitis A antibody levels were significantly increased in five counties, which indicates a successful result of EPI.

A practical community-based response strategy to interrupt Ebola transmission in sierra Leone, 2014-2015.

BACKGROUND: The Ebola virus disease spread rapidly in West Africa in 2014, leading to the loss of thousands of lives. Community engagement was one of the key strategies to interrupt Ebola transmission, and practical community level measures needed to be explored in the field and tailored to the specific context of communities. METHODS: First, community-level education on Ebola virus disease (EVD) prevention was launched for the community's social mobilizers in six districts in Sierra Leone beginning in November 2014. Then, from January to May of 2015, in three pilot communities, local trained community members were organized to engage in implementation of EVD prevention and transmission interruption measures, by involving them in alert case report, contact tracing, and social mobilization. The epidemiological indicators of transmission interruption in three study communities were evaluated. RESULTS: A total of 6 016 community social mobilizers from 185 wards were trained by holding 279 workshops in the six districts, and EVD message reached an estimated 631 680 residents. In three pilot communities, 72 EVD alert cases were reported, with 70.8 % of them detected by trained local community members, and 14 EVD cases were finally identified. Contact tracing detected 64.3 % of EVD cases. The median duration of community infectivity for the cases was 1 day. The secondary attack rate was 4.2 %, and no third generation of infection was triggered. No health worker was infected, and no unsafe burial and noncompliance to EVD control measures were recorded. The community-based measures were modeled to reduce 77 EVD cases, and the EVD-free goal was achieved four months earlier in study communities than whole country of Sierra Leone. CONCLUSIONS: The community-based strategy of social mobilization and community engagement was effective in case detection and reducing the extent of Ebola transmission in a country with weak health system. The successfully practical experience to reduce the risk of Ebola transmission in the community with poor resources would potentially be helpful for the global community to fight against the EVD and the other diseases in the future.

Epidemiological investigation of measles in sera of healthy people in Heilongjiang Province, China.

Serological samples of healthy people were collected to obtain the levels of measles antibodies in different groups of people in Heilongjiang Province, China. Using quantitative enzyme-linked immunosorbent assays to measure the antibody levels, we found the lowest antibody positive rate and the lowest geometric mean concentration values in healthy people aged 15-39. This group is the population at high risk for adult measles in Heilongjiang Province, and is the focus of measles elimination work. The new challenges for the eventual elimination of measles will be to address immunization strategies in this segment of the population in order to control the incidence.

[Analysis on surveillance data regarding the level of Japanese encephalitis antibody in Heilongjiang. province, 2006].

OBJECTIVE: To study the prevalent situation of Japanese encephalitis (JE) virus among healthy people in Heilongjiang province and to analyze its risk factors. METHODS: 7 national surveillance counties were selected and divided into 5 age groups as 1-2, 3-5, 6-10, 11-20 and 21-59 years and randomly sampled 7 person in each age group per county with the sample size as 1050. Quantitative Elisa test was used to detect Japanese encephalitis antibody IgG. RESULTS: The adjusted standard antibody positive rate of people on 1-59 year olds was 70.62%, with lowest in 3-5 age group, and increasing by age (chi2 for trend test = 40.52, P < 0.001). The overall titer of IgG was low in general population but was different with age (Kruskal-Wallis test chi2 = 76.9, P < 0.001). Older age and lower latitude seemed to be two risk factors on JE antibody IgG. CONCLUSION: JE virus infection had a long-term effect with low level, among general population. Age and latitude were two risk factors which suggesting the necessarily of strengthening the surveillance system for JE cases at risk in the prevalent areas on Heilongjiang province.