Identification of immune activation-related gene signature for predicting prognosis and immunotherapy efficacy in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is a major subtype of non-small cell lung cancer (NSCLC) with a highly heterogeneous tumor microenvironment. Immune checkpoint inhibitors (ICIs) are more effective in tumors with a pre-activated immune status. However, the potential of the immune activation-associated gene (IAG) signature for prognosis prediction and immunotherapy response assessment in LUAD has not been established. Therefore, it is critical to explore such gene signatures. Methods: RNA sequencing profiles and corresponding clinical parameters of LUAD were extracted from the TCGA and GEO databases. Unsupervised consistency clustering analysis based on immune activation-related genes was performed on the enrolled samples. Subsequently, prognostic models based on genes associated with prognosis were built using the last absolute shrinkage and selection operator (LASSO) method and univariate Cox regression. The expression levels of four immune activation related gene index (IARGI) related genes were validated in 12 pairs of LUAD tumor and normal tissue samples using qPCR. Using the ESTIMATE, TIMER, and ssGSEA algorithms, immune cell infiltration analysis was carried out for different groups, and the tumor immune dysfunction and rejection (TIDE) score was used to evaluate the effectiveness of immunotherapy. Results: Based on the expression patterns of IAGs, the TCGA LUAD cohort was classified into two clusters, with those in the IAG-high pattern demonstrating significantly better survival outcomes and immune cell infiltration compared to those in the IAG-low pattern. Then, we developed an IARGI model that effectively stratified patients into different risk groups, revealing differences in prognosis, mutation profiles, and immune cell infiltration within the tumor microenvironment between the high and low-risk groups. Notably, significant disparities in TIDE score between the two groups suggest that the low-risk group may exhibit better responses to ICIs therapy. The IARGI risk model was validated across multiple datasets and demonstrated exceptional performance in predicting overall survival in LUAD, and an IARGI-integrated nomogram was established as a quantitative tool for clinical practice. Conclusion: The IARGI can serve as valuable biomarkers for evaluating the tumor microenvironment and predicting the prognosis of LUAD patients. Furthermore, these genes probably provide valuable guidance for establishing effective immunotherapy regimens for LUAD patients.

Investigation of two norovirus outbreaks linked to drinking water contaminated with multiple GII strains in a rural county-Chongqing, China, 2021.

Backgrounds: Norovirus is leading cause of non-bacterial gastroenteritis outbreaks globally, characterized by different strains prevalent in different countries and regions. Methods: Cases were defined as individuals experiencing diarrhea ≥3 times/24 h, and/or vomiting ≥2 times/24 h in two villages between January 28 and February 9, 2021. Investigations were conducted to identify causes. Cases were interviewed using a standardized in-person form to collect data on potential risk factors. A retrospective cohort study was conducted to investigate the role of the spring water supply as the outbreak source. Residents from neighboring villages with different water sources served as the unexposed population. Stool specimens, rectal swabs, and water samples were tested using quantitative real-time Polymerase Chain Reaction, with subsequent sequencing performed on pathogen-positive specimens. Results: Village-specific attack rates were 21.93% (123/561) and 26.99% (88/326), respectively. Evidence from both epidemiological and laboratory tests was consistent. Drinking spring water was statistically associated with the two outbreaks (RR = 41.8 and 79.2, respectively). In both outbreaks, stool specimens, rectal swabs, and water samples tested positive for norovirus. Specifically, GII.2 (P16) and GII.17 (P17) were identified in outbreak A, and GII.4 Sydney (P16) and GII.1 (P16) in outbreak B. Conclusion: These two independent gastroenteritis outbreaks share similarities, both being linked to norovirus GII strains. The contaminated spring drinking water was identified as the probable source and was promptly closed and subjected to disinfection procedures. These findings reinforce the importance of implementing sanitation and environmental disinfection measures in rural areas, especially during the periods of increased rainfall.

An Outbreak of SARS-CoV-2 Omicron Subvariant BA.2.76 in an Outdoor Park - Chongqing Municipality, China, August 2022.

What is already known about this topic?: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant has a stronger transmission capacity and faster transmission speed than the previous strain. What is added by this report?: The first coronavirus disease 2019 (COVID-19) case infected with the SARS-CoV-2 Omicron subvariant BA.2.76 who caused local transmission was reported in Chongqing Municipality on August 16, 2022. For 35 minutes, the Patient Zero jogged along a lake at a local park without wearing a mask. Among the 2,836 people potentially exposed at the time, 39 tested positive. Overall, 38 out of 39 cases did not wear a mask on the morning of August 16. All 39 cases lacked any previous exposure to the variant before testing positive on their nucleic acid test. What are the implications for public health practice?: It is essential to maintain personal wellbeing by ensuring one maintains personal protection and follows regulated guidelines such as maintaining safe distances from others both indoors and outdoors.

Immunotherapy and Prevention of Cancer by Nanovaccines Loaded with Whole-Cell Components of Tumor Tissues or Cells.

Tumor tissues/cells are the best sources of antigens to prepare cancer vaccines. However, due to the difficulty of solubilization and delivery of water-insoluble antigens in tumor tissues/cells, including water-insoluble antigens into cancer vaccines and delivering such vaccines efficiently to antigen-presenting cells (APCs) remain challenging. To solve these problems, herein, water-insoluble components of tumor tissues/cells are solubilized by 8 m urea and thus whole components of micrometer-sized tumor cells are reasssembled into nanosized nanovaccines. To induce maximized immunization efficacy, various antigens are loaded both inside and on the surface of nanovaccines. By encapsulating both water-insoluble and water-soluble components of tumor tissues/cells into nanovaccines, the nanovaccines are efficiently phagocytosed by APCs and showed better therapeutic efficacy than the nanovaccine loaded with only water-soluble components in melanoma and breast cancer. Anti-PD-1 antibody and metformin can improve the efficacy of nanovaccines. In addition, the nanovaccines can prevent lung cancer (100%) and melanoma (70%) efficiently in mice. T cell analysis and tumor microenvironment analysis indicate that tumor-specific T cells are induced by nanovaccines and both adaptive and innate immune responses against cancer cells are activated by nanovaccines. Overall, this study demonstrates a universal method to make tumor-cell-based nanovaccines for cancer immunotherapy and prevention.

Epidemiological analysis of norovirus infectious diarrhea outbreaks in Chongqing, China, from 2011 to 2016.

OBJECTIVE: We investigated the epidemiological characteristics of norovirus infection from 2011 to 2016 in Chongqing, China, in order to provide evidence for strategies on epidemic prevention and control. METHODS: We collected data on norovirus infectious diarrhea epidemics in 38 districts and counties, and analyzed the information using descriptive epidemiological methods. RESULTS: In 2011, the first case of norovirus infectious diarrhea in Chongqing was reported. From 2011 to 2015, 38 districts and counties in Chongqing reported a total of 4 epidemics. In 2016, however, the city reported 117 outbreaks. From 2011 to 2016, there were 1637 cases of norovirus infection but no deaths. In 2016, most outbreaks occurred over a 5-month period with a clear peak in December and higher incidence in major urban areas than smaller communities (83.61% vs. 16.39%). Of these 1637 cases, 99.18% occurred in urban schools and nurseries, and 80% were transmitted person-to-person. Infection by genogroup II genotype 2 (GII.2) viruses accounted for 98.71% of cases. Leukocytes were increased in 67.81% of patients, neutrophils in 65%, and lymphocytes in 50%. Medical treatment was sought by 70% of patients or guardians but only 3.66% of cases were hospitalized. The most frequent misdiagnosis was "suspected food poisoning". CONCLUSION: The frequency of norovirus infectious diarrhea epidemics increased over 20-fold from 2011 to 2016 in Chongqing, China. These epidemics occurred predominantly in urban schools and nurseries. However, epidemics showed little spread to outlying districts and counties, so prevention and control pressures were relatively high. SUGGESTIONS: Healthcare professionals and institutions should strengthen health education for groups at high-risk of norovirus infection, such as school children, and increase norovirus testing capacity to further improve emergency investigation. Prevention and control knowledge should be disseminated to the general public to reduce transmission risk and total disease burden. Finally, governments and health administrative departments should invest special funds to prevent and control norovirus epidemics.

Domino N-/C- or N-/N-/C-arylation of imidazoles to yield polyaryl imidazolium salts via atom-economical use of diaryliodonium salts.

Herein, we disclose a Cu-mediated domino di-/triarylation reaction of imidazoles to efficiently access polyaryl imidazolium salts in a single step by using two aryls as well as an anion of a diaryliodonium salt. The diarylation shows high atom economy and excellent selectivity with unsymmetrical iodonium salts.

Influenza A(H7N9) virus emerged and resulted in human infections in Chongqing, southwestern China since 2017.

OBJECTIVES: Influenza A(H7N9) virus has emerged and resulted in human infections in Chongqing, southwestern China since 2017. This study aimed to describe the epidemiological characteristics of the first epidemic in this region. METHODS: The epidemiological data of patients were collected. Live poultry markets (LPMs), commercial poultry farms (CPFs) and backyard poultry farms (BPFs) were monitored, and poultry sources were registered. Samples derived from the patients, their close contacts, and the environments were tested for influenza A(H7N9) virus by real-time reverse transcriptase polymerase chain reaction. Genetic sequencing and phylogenetic analysis were also conducted. RESULTS: Since the confirmation of the first patient infected with influenza A(H7N9) virus on March 5, 2017, nine patients had been identified within four months in Chongqing. Their mean age was 45 years, 77.8% were male, 66.7% were urban residents and 55.6% were of poultry related occupation. All patients became infected after exposure to live chickens. The median time interval from initial detection of influenza A(H7N9) virus in Chongqing to the patients' onset was 75 days. Since initial detection in February 2017, influenza A(H7N9) virus was detected in 21 (53.8%) counties within four months. The proportion of positive samples was 2.94% (337/11,451) from February 2017 to May 2018, and was higher (χ2=75.78, P<0.001) in LPMs (3.66%, 329/8979) than that in CPFs (0.41%, 5/1229) and BPFs (0.24%, 3/1243). The proportion of positive samples (34.4%, 22/64) at the premises to which the patients were exposed was significantly higher than that (5.7%, 257/4474) in premises with no patients. Phylogenetic analysis indicated that the viruses isolated in Chongqing belonged to the Yangtze River Delta lineage and resembled those circulated in Jiangsu and Anhui provinces between late 2016 and early 2017. CONCLUSION: Influenza A(H7N9) virus was newly introduced into Chongqing most likely between late 2016 and early 2017, which swept across half of Chongqing territory and resulted in human infections within months. The most impacted premises and population were LPMs and poultry related workers respectively in the epidemic.

The prognostic value of abnormally expressed lncRNAs in prostatic carcinoma: A systematic review and meta-analysis.

BACKGROUND: Several long noncoding RNAs (lncRNAs) are abnormally expressed in prostate cancer (PCa), suggesting that they could serve as novel prognostic markers. The current meta-analysis was undertaken to better define the prognostic value of various lncRNAs in PCa. METHODS: The PubMed, Embase, Medline, and Cochrane Library databases were systematically searched up to February 19, 2017, to retrieve eligible articles. Outcomes analyzed were biochemical recurrence-free survival (BRFS), overall survival (OS), metastasis-free survival (MFS), and prostate cancer-specific survival (PCSS). Pooled hazard ratios (HRs) and 95% confidence intervals (95%CIs) were calculated using fixed-effects or random-effects models. RESULTS: A total of 10 studies, evaluating 11 PCa-related lncRNAs, were included in the meta-analysis. Pooled results indicate that the abnormal expression of candidate lncRNAs in PCa samples predicted poor BRFS (HR: 1.67, 95%CI: 1.37-2.04, P < .05), without significant heterogeneity among studies (I = 44%, P = .06). Low PCAT14 expression was negatively associated with OS (HR: 0.66, 95%CI: 0.54-0.79, P < .05), MFS (HR: 0.59, 95%CI: 0.48-0.72, P < .05), and PCSS (HR: 0.50, 95%CI: 0.38-0.66, P < .05). Again, there was no significant heterogeneity among studies. The robustness of our results was confirmed by sensitivity and publication bias analyses. CONCLUSION: We conclude that expression analysis of selected lncRNAs may be of prognostic value in PCa patients.