Aspartoacylase promotes the process of tumour development and is associated with immune infiltrates in gastric cancer.

BACKGROUND: Aspartoacylase (ASPA) is a gene that plays an important role in the metabolic reprogramming of cancer. However, the clinical relevance of ASPA in gastric cancer (GC) has not been demonstrated. METHODS: The link between ASPA and the clinical features of GC was determined using two public genomic databases. The multivariate Cox proportional hazard model and generalised linear regression model were applied to examine whether the ASPA level is associated with the prognosis and other pathological factors. In addition, the role of specific genes in the infiltration of immune cells in the setting of GC was investigated using a further immunological database. The expression level of various proteins was detected using a western blotting assay. Transwell and methyl thiazolyl tetrazolium tests were applied for the detection of cellular invasion and proliferation, with small hairpin ribonucleic acid used to knockdown ASPA. RESULTS: According to the multivariate Cox regression results, the down-regulated ASPA expression is a distinct prognostic factor. Furthermore, ASPA has significant positive correlations with the infiltration of immune cells in GC lesions. Compared to the non-cancer tissues, the GC tissues had a significantly lower level of ASPA expression (p < 0.05). Using knockdown and overexpression techniques, it was demonstrated that ASPA affects the capacity of cell lines for GC to both proliferate and invade. CONCLUSION: Overall, ASPA could promote the occurrence and development of GC and presents a promising predictive biomarker for the disease since it is favourably connected with immune infiltrates and negatively correlated with prognosis.

The effect of ambient temperature on hand, foot and mouth disease in Qingdao, China, 2014-2018.

Hand, foot, and mouth disease (HFMD) is a kind of infection gastrointestinal disease. The present study aims to explore the association between ambient temperature and HFMD in Qingdao. A distributed lag nonlinear model with Poisson distribution was adopted to explore the effects of daily mean temperature on HFMD incidence. Our results found that the high temperature had acute and short-term effects and then declined rapidly along the lag days, with the maximum risk occurring 0 day of exposure. Compared with low temperature, higher effects were observed for high-temperature exposure. Overall, we found that the association between temperature and HFMD incidence was non-linear, exhibiting an approximate "J" shape, with peak value occurring at 30.5℃ (RR = 2.208, 95% CI: 1.995-2.444). Our findings suggest that ambient temperature is significantly associated with the incidence of HFMD in Qingdao. Monitoring ambient temperature changes is an appropriate recommendation to prevent HFMD.

Immunodeficiencies Push Readmissions in Malignant Tumor Patients: A Retrospective Cohort Study Based on the Nationwide Readmission Database.

BACKGROUND: Immunodeficiency diseases (IDDs) are associated with an increased proportion of cancer-related morbidity. However, the relationship between IDDs and malignancy readmissions has not been well described. Understanding this relationship could help us to develop a more reasonable discharge plan in the special tumor population. METHODS: Using the Nationwide Readmissions Database, we established a retrospective cohort study that included patients with the 16 most common malignancies, and we defined two groups: non-immunodeficiency diseases (NOIDDs) and IDDs. RESULTS: To identify whether the presence or absence of IDDs was associated with readmission, we identified 603,831 patients with malignancies at their time of readmission in which 0.8% had IDDs and in which readmission occurred in 47.3%. Compared with NOIDDs, patients with IDDs had a higher risk of 30-day (hazard ratio (HR) of 1.32; 95% CI of 1.25-1.40), 90-day (HR of 1.27; 95% CI of 1.21-1.34) and 180-day readmission (HR of 1.28; 95% CI of 1.22-1.35). More than one third (37.9%) of patients with IDDs had readmissions that occurred within 30 days and most (82.4%) of them were UPRs. An IDD was an independent risk factor for readmission in patients with colorectal cancer (HR of 1.32; 95% CI of 1.01-1.72), lung cancer (HR of 1.23; 95% CI of 1.02-1.48), non-Hodgkin's lymphoma (NHL) (HR of 1.16; 95% CI of 1.04-1.28), prostate cancer (HR of 1.45; 95% CI of 1.07-1.96) or stomach cancer (HR of 2.34; 95% CI of 1.33-4.14). Anemia (44.2%), bacterial infections (28.6%) and pneumonia (13.9%) were the 30-day UPR causes in these populations. (4) Conclusions: IDDs were independently associated with higher readmission risks for some malignant tumors. Strategies should be considered to prevent the causes of readmission as a post discharge plan.

Association of CSMD1 with Tumor Mutation Burden and Other Clinical Outcomes in Gastric Cancer.

BACKGROUND: Immunotherapy is considered as a powerful and promising clinical approach for the treatment of gastric cancer (GC). However, it is still challenging to precisely screen patients who potentially benefit from immune checkpoint therapy (ICT). Identification of potential biomarkers for selecting patients sensitive to immunotherapy was urgently needed. METHODS: Public sequence data and corresponding clinical data were used to explore the potential biomarkers for immunotherapy. RESULTS: We found that CSMD1 is the most frequently mutated gene and its mutation is highly correlated with prognosis in gastric cancer patients. Interestingly, patients with mutated CSMD1 exhibit a high mutation burden and upregulated PDL1 expression. The ratio of microsatellite instability (MSI) in the CSMD1 mutation cohort was higher than that in the cohort without CSMD1 mutation. Furthermore, patients with CSMD1 mutation have been found to possess a higher number of activated CD4+ T cells and neoantigens. CONCLUSION: CSMD1 mutation may act as a novel biomarker for assessing the survival and immune therapy response in patients with gastric cancer.

The association between ambient air pollution and scarlet fever in Qingdao, China, 2014-2018: a quantitative analysis.

BACKGROUND: We conducted a distributed lag non-linear time series analysis to quantify the association between air pollution and scarlet fever in Qingdao city during 2014-2018. METHODS: A distributed lag non-linear model (DLNM) combined with a generalized additive mixed model (GAMM) was applied to quantify the distributed lag effects of air pollutions on scarlet fever, with daily incidence of scarlet fever as the dependent variable and air pollutions as the independent variable adjusted for potential confounders. RESULTS: A total of 6316 cases of scarlet fever were notified, and there were 376 days occurring air pollution during the study period. Scarlet fever was significantly associated with air pollutions at a lag of 7 days with different relative risk (RR) of air pollution degrees [1.172, 95% confidence interval (CI): 1.038-1.323 in mild air pollution; 1.374, 95% CI 1.078-1.749 in moderate air pollution; 1.610, 95% CI 1.163-2.314 in severe air pollution; 1.887, 95% CI 1.163-3.061 in most severe air pollution]. CONCLUSIONS: Our findings show that air pollution is positively associated with scarlet fever in Qingdao, and the risk of scarlet fever could be increased along with the degrees of air pollution. It contributes to developing strategies to prevent and reduce health impact from scarlet fever and other non-vaccine-preventable respiratory infectious diseases in air polluted areas.

Association between floods and the risk of dysentery in China: a meta-analysis.

The association between floods and the risk of dysentery remain controversial. Therefore, we performed a meta-analysis to clarify this relationship. A literature search was performed in PubMed, Web of science, and Embase for relevant articles published up to November 2019. Random-effects model was used to pool relative risks with 95% confidence intervals. The sensitivity analysis was carried out to evaluate the stability of the results. Publication bias was estimated using Egger's test. Eleven studies from 10 articles evaluated the association between floods and the risk of dysentery in China. The pooled RR (95% CI) of dysentery for the flooded time versus non-flooded period was 1.48 (95% CI: 1.14-1.91). Significant association was found in subgroup analysis stratified by dysentery styles [dysentery: 1.61 (95% CI: 1.34-1.93) and bacillary dysentery: 1.46 (95% CI: 1.06-2.01)]. The pooled RR (95%CI) of sensitivity analysis for dysentery was 1.26 (95% CI: 1.05-1.52). No significant publication bias was found in our meta-analysis. This meta-analysis confirms that floods have significantly increased the risk of dysentery in China. Our findings will provide more evidence to reduce negative health outcomes of floods in China.

Risk factors associated with occurrence of COVID-19 among household persons exposed to patients with confirmed COVID-19 in Qingdao Municipal, China.

Tracing and isolation of close contacts is used to control outbreaks of coronavirus disease 2019 (COVID-19) in China. However, risk factors associated with the occurrence of COVID-19 among close contacts have not been well described. A total of 106 household contacts were included in this study, of whom 19 developed into COVID-19 cases, and the secondary attack rate was 17.9%. Multivariable analysis showed that increasing risk of occurrence of COVID-19 among household contacts was associated with female index patients (adjusted hazard ratio [aHR] = 3.84, 95% CI = 1.07-13.78), critical disease index patients (aHR = 7.58, 95% CI = 1.66-34.66), effective contact duration with index patients > 2 days (aHR = 4.21, 95% CI = 1.29-13.73), and effective contact duration > 11 days (aHR = 17.88, 95% CI = 3.26-98.01). The sex and disease severity of index patients with COVID-19 and longer effective contact duration with patients with confirmed COVID-19 could help epidemiologists to identify potential COVID-19 cases among household contacts at an early stage.

Hepatitis E outbreak in a mechanical factory in Qingdao City, China.

OBJECTIVE: In July 2018, recurrent hepatitis E cases were reported from a factory in Qingdao City, China. The aim of this study was to identify additional cases, and help prevent future incidents by identifying possible risk factors for infection. METHODS: Participants were asked to provide blood samples for hepatitis E virus (HEV) IgM and IgG antibodies screening, as well as liver function test. A questionnaire that assessed demographics, potential risk factors, and clinical symptoms was completed by participants. HEV RNA genotyping was performed using a nested Reverse Transcriptional Polymerase Chain Reaction (RT-PCR) method. Adjusted Poisson regression model for participant characteristics and risk factors was constructed for multivariate analysis. RESULTS: Overall, 41(14.5%, 41/283) participants had recent acute infection (21 of these were symptomatic). The result of multivariate analysis demonstrated a significant association of acute HEV infection with consumption of pig liver within the past two months (Relative Risk 2.61, 95% confidence interval (CI) 1.10-6.17, p=0.0294). Sequencing of HEV RNA from seventeen acute cases indicated three HEV isolates of genotype 4 induced this outbreak. CONCLUSIONS: This was probably a common-source foodborne hepatitis E outbreak, related to the consumption of undercooked pig liver.

Lysyl oxidase and hypoxia-inducible factor 1α: biomarkers of gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the main causes of cancer mortality worldwide. Recent studies on tumor microenvironments have shown that tumor metabolism exerts a vital role in cancer progression. AIM: To investigate whether lysyl oxidase (LOX) and hypoxia-inducible factor 1α (HIF1α) are prognostic and predictive biomarkers in GC. METHODS: A total of 80 tissue and blood samples were collected from 140 patients admitted to our hospital between August 2008 and March 2012. Immunohistochemical staining was performed to measure the expression of LOX and HIF1α in tumor and adjacent tissues collected from patients with GC. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was used to detect the mRNA expression levels of LOX and HIF1α in patients with GC. In addition, single-factor analysis was applied to analyze the relationship between LOX, HIF1α and prognosis of GC. RESULTS: Immunohistochemical staining suggested that the expression levels of LOX and HIF1α increased in tumor tissues from patients with GC. QRT-PCR analysis indicated that mRNA expression of LOX and HIF1α was also upregulated in tumor tissues, which was in accordance with the above results. We also detected expression of these two genes in blood samples. The expression level of LOX and HIF1α was higher in patients with GC than in healthy controls. Additional analysis showed that the expression level of LOX and HIF1α was related to the clinicopathological characteristics of GC. Expression of LOX and HIF1α increased with the number of lymph node metastases , deeper infiltration depth and later tumor-node-metastasis stages. Single-factor analysis showed that high expression of LOX and HIF1α led to poor prognosis of patients with GC. CONCLUSION: LOX and HIF1α can be used as prognostic and predictive biomarkers for GC.

Meteorological factors affect the epidemiology of hemorrhagic fever with renal syndrome via altering the breeding and hantavirus-carrying states of rodents and mites: a 9 years' longitudinal study.

The incidence of hemorrhagic fever with renal syndrome (HFRS) in Qingdao, China was three times higher than that of the average national level. Here we characterized the epidemiology, ecological determinants and pathogen evolution of HFRS in Qingdao during 2007-2015. In this longitudinal study, a total of 1846 HFRS patients and 41 HFRS-related deaths were reported. HFRS in Qingdao peaked once a year in the fourth quarter. We built a time series generalized additive model, and found that meteorological factors in the previous quarter could accurately predict HFRS occurrence. To explore how meteorological factors influenced the epidemic of HFRS, we analyzed the relationship between meteorological factors and hantavirus-carrying states of the hosts (including rodents and shrews). Comprehensive analysis showed humidity was correlated to high host densities in the third quarter and high hantavirus-carrying rates of animal hosts in the third to fourth quarters, which might contribute to HFRS peak in the fourth quarter. We further compared the L segments of hantaviruses from HFRS patients, animal hosts and ectoparasites. Phylogenetic analysis showed that hantaviruses in gamasid and trombiculid mites were the same as those from the hosts. This indicated mites also contributed to the transmission of hantavirus. Furthermore, Hantaan virus from HFRS patients, hosts and mites in Qingdao formed a distinct phylogenetic cluster. A new clade of Seoul virus was also identified in the hosts. Overall, meteorological factors increase HFRS incidence possibly via facilitating hosts' reproduction and consequent mite-mediated hantavirus transmission. New hantavirus subtypes evolved in Qingdao represent new challenges of fighting against HFRS.

Evaluation of docetaxel- and oxaliplatin-based adjuvant chemotherapy in postgastrectomy gastric cancer patients reveals obvious survival benefits in docetaxel-treated mixed signet ring cell carcinoma patients.

The purpose of this study was to determine the disease-free and overall survival (DFS and OS, respectively) in 991 postgastrectomy gastric cancer patients untreated (n = 372) or treated with either oxaliplatin-based (n = 376) or docetaxel-based (n = 243) chemotherapy and to identify prognostic factors that could help establish subgroups of patients who would benefit from such treatment. The median follow-up duration was 55.3 months (range 31.2-90.8 months). Subgroup analyses revealed that gastric adenocarcinoma (DFS 56.9 vs 53.2 months, P = 0.180, χ(2) = 1.802; OS not reached vs 70.7 months, P = 0.521, χ(2) = 0.412), but not absolute signet ring cell (SRC) carcinoma (DFS 15.1/18.0 vs 10.1 months, P = 0.171/0.259, χ(2) = 1.874/1.275; OS 21.0/26.1 vs 20.5 months, P = 0.551/0.196, χ(2) = 0.355/1.674), patients undergoing either docetaxel- or oxaliplatin-based chemotherapy had a lower risk of recurrence and increased survival in comparison to those without chemotherapy. In the mixed SRC carcinoma patients, DFS and OS of patients treated with docetaxel-based regimen had a longer survival (DFS 50.1 vs 29.9 months, P = 0.046, χ(2) = 3.987; OS not reached vs 48.6 months, P = 0.016, χ(2) = 5.854) and lower risk of recurrence and death (DFS HR 0.540, 95 % CI 0.355-0.874, P = 0.012; OS HR 0.452, 95 % CI 0.259-0.790, P = 0.005) than oxaliplatin-based chemotherapy. Cumulatively, our results indicate that adjuvant chemotherapy is beneficial and that docetaxel-based regimen should be considered for patients with mixed SRC carcinoma.

HIF-1 alpha overexpression correlates with poor overall survival and disease-free survival in gastric cancer patients post-gastrectomy.

BACKGROUND: Overall, gastric cancer prognosis remains poor. Detailed characterization of molecular markers that govern gastric cancer pathogenesis is warranted to establish innovative therapeutic options. HIF-1α overexpression has been linked to poor gastric cancer prognosis. However, though researched for years, the prognostic role of HIF-1α in gastric cancer is still controversial. Hence, the objective of the present study was to analyze the prognostic values of HIF-1α, TGF-ß, VEGF and pERK1/2 in gastric cancer patients following gastrectomy. METHODS: This study included 446 patients with confirmed gastric cancer who underwent gastrectomy in a single Chinese Cancer Center between 2005 and 2006. Clinicopathologic features, as well as immunohistochemical analysis of TGF-ß, HIF-1α, VEGF and pERK1/2 were determined. Long-term survival of these patients was analyzed using univariate and multivariate analyses. RESULTS: HIF-1α overexpression was more frequent in patients with hepatic metastases (71.6% versus 43.0% in those without hepatic metastases, P = 0.000, χ2 = 23.086) and more frequent in patients with peritoneum cavity metastasis (62.3% versus 43.0% in those without such metastasis, P = 0.000, χ2 = 13.691). In univariate analysis, patients with HIF-1α overexpression had a shorter disease-free survival (DFS) and overall survival (OS) than patients with weak-expression (DFS: NA VS. 16.8 m, P = 0.000, χ2 = 74.937; OS: NA VS. 25.5 m, P = 0.000, χ2 = 90.594). Importantly, HIF-1α overexpression was a promising prognostic marker for poor survival by multivariate analysis (DFS: HR 2.766, 95%CI 2.136-2.583, P = 0.000; OS: HR 3.529, 95%CI 2.663-4.667, P = 0.000). CONCLUSIONS: HIF-1α overexpression could be considered a useful independent prognostic biomarker in gastric cancer after gastrectomy, and is correlated to both a poor overall survival and disease-free survival in these patients. HIF-1α expression can be used to stratify patients at higher risk for poor prognosis, and is potentially an important therapeutic target in gastric cancer patients.