Assessing the causal relationship between COVID-19 and post-COVID-19 syndrome: A Mendelian randomisation study.

Background: In the aftermath of the coronavirus disease 2019 (COVID-19) pandemic, we sought to explore the causal association between COVID-19 and 17 prevalent post-COVID-19 syndrome (PCS) symptoms using Mendelian randomisation (MR) methodology. Methods: We used 22 extensive genome-wide association study (GWAS) data sets, incorporating genetic variants as instrumental variables. Univariate Mendelian randomisation (UVMR) analyses involved 15 single nucleotide polymorphisms (SNPs) for COVID-19 patients, 33 for hospitalised COVID-19 patients, and 29 for patients with severe respiratory symptoms due to COVID-19. Furthermore, we further used multivariable Mendelian randomisation (MVMR) analyses based on 93 SNPs for COVID-19 patients, 105 for hospitalised COVID-19 patients, and 99 for patients with severe respiratory symptoms due to COVID-19. With these analyses, we aimed to assess the causal associations between varying levels of COVID-19 infection and 17 prevalent PCS symptoms while accounting for the influence of educational and income levels. Results: UVMR analysis identified potential causal effects of COVID-19 genetic susceptibility on myalgia and pain in various regions. Hospitalised COVID-19 was potentially linked to erectile dysfunction and alopecia areata. Very severe respiratory confirmed patients exhibited increased pain and tobacco use. Meanwhile, the MVMR analysis demonstrated a potential causal link between hospitalised COVID-19 and heart arrhythmia, and a protective effect of COVID-19 on tobacco use after adjusting for educational and income levels. Conclusions: Our MR analysis provides compelling evidence of causal associations between genetic susceptibility to COVID-19 and specific PCS symptoms, in which educational and income levels play a mediating role. These findings shed light on PCS pathogenesis and underscore the importance of considering social factors in its management. Tailored interventions and policies are crucial for PCS-affected individuals' well-being. Further research is needed to explore the impact of social determinants on COVID-19 patients and the wider population.

Prevalence, risk factors, impact and management of pneumonia among preschool children in Chinese seven cities: a cross-sectional study with interrupted time series analysis.

BACKGROUND: Pneumonia is a common disease worldwide in preschool children. Despite its large population size, China has had no comprehensive study of the national prevalence, risk factors, and management of pneumonia among preschool children. We therefore investigated the prevalence of pneumonia among preschool children in Chinese seven representative cities, and explore the possible risk factors of pneumonia on children, with a view to calling the world's attention to childhood pneumonia to reduce the prevalence of childhood pneumonia. METHODS: Two group samples of 63,663 and 52,812 preschool children were recruited from 2011 and 2019 surveys, respectively. Which were derived from the cross-sectional China, Children, Homes, Health (CCHH) study using a multi-stage stratified sampling method. This survey was conducted in kindergartens in seven representative cities. Exclusion criteria were younger than 2 years old or older than 8 years old, non-permanent population, basic information such as gender, date of birth and breast feeding is incomplete. Pneumonia was determined on the basis of parents reported history of clearly diagnosed by the physician. All participants were assessed with a standard questionnaire. Risk factors for pneumonia, and association between pneumonia and other respiratory diseases were examined by multivariable-adjusted analyses done in all participants for whom data on the variables of interest were available. Disease management was evaluated by the parents' reported history of physician diagnosis, longitudinal comparison of risk factors in 2011 and 2019. RESULTS: In 2011 and 2019, 31,277 (16,152 boys and 15,125 girls) and 32,016 (16,621 boys and 15,395 girls) preschool children aged at 2-8 of permanent population completed the questionnaire, respectively, and were thus included in the final analysis. The findings showed that the age-adjusted prevalence of pneumonia in children was 32.7% in 2011 and 26.4% in 2019. In 2011, girls (odds ratio [OR] 0.91, 95%CI [confidence interval]0.87-0.96; p = 0.0002), rural (0.85, 0.73-0.99; p = 0.0387), duration of breastfeeding ≥ 6 months(0.83, 0.79-0.88; p < 0.0001), birth weight (g) ≥ 4000 (0.88, 0.80-0.97; p = 0.0125), frequency of putting bedding to sunshine (Often) (0.82, 0.71-0.94; p = 0.0049), cooking fuel type (electricity) (0.87, 0.80-0.94; p = 0.0005), indoor use air-conditioning (0.85, 0.80-0.90; p < 0.0001) were associated with a reduced risk of childhood pneumonia. Age (4-6) (1.11, 1.03-1.20; p = 0.0052), parental smoking (one) (1.12, 1.07-1.18; p < 0.0001), used antibiotics (2.71, 2.52-2.90; p < 0.0001), history of parental allergy (one and two) (1.21, 1.12-1.32; p < 0.0001 and 1.33, 1.04-1.69; p = 0.0203), indoor dampness (1.24, 1.15-1.33; p < 0.0001), home interior decoration (1.11, 1.04-1.19; p = 0.0013), Wall painting materials (Paint) (1.16, 1.04-1.29; p = 0.0084), flooring materials (Laminate / Composite wood) (1.08, 1.02-1.16; p = 0.0126), indoor heating mode(Central heating)(1.18, 1.07-1.30, p = 0.0090), asthma (2.38, 2.17-2.61; p < 0.0001), allergic rhinitis (1.36, 1.25-1.47; p < 0.0001), wheezing (1.64, 1.55-1.74; p < 0.0001) were associated with an elevated risk of childhood pneumonia; pneumonia was associated with an elevated risk of childhood asthma (2.53, 2.31-2.78; p < 0.0001), allergic rhinitis (1.41, 1.29-1.53; p < 0.0001) and wheezing (1.64, 1.55-1.74; p < 0.0001). In 2019, girls (0.92, 0.87-0.97; p = 0.0019), duration of breastfeeding ≥ 6 months (0.92, 0.87-0.97; p = 0.0031), used antibiotics (0.22, 0.21-0.24; p < 0.0001), cooking fuel type (Other) (0.40, 0.23-0.63; p = 0.0003), indoor use air-conditioning (0.89, 0.83-0.95; p = 0.0009) were associated with a reduced risk of childhood pneumonia. Urbanisation (Suburb) (1.10, 1.02-1.18; p = 0.0093), premature birth (1.29, 1.08-1.55; p = 0.0051), birth weight (g) < 2500 (1.17, 1.02-1.35; p = 0.0284), parental smoking (1.30, 1.23-1.38; p < 0.0001), history of parental asthma (One) (1.23, 1.03-1.46; p = 0.0202), history of parental allergy (one and two) (1.20, 1.13-1.27; p < 0.0001 and 1.22, 1.08-1.37; p = 0.0014), cooking fuel type (Coal) (1.58, 1.02-2.52; p = 0.0356), indoor dampness (1.16, 1.08-1.24; p < 0.0001), asthma (1.88, 1.64-2.15; p < 0.0001), allergic rhinitis (1.57, 1.45-1.69; p < 0.0001), wheezing (2.43, 2.20-2.68; p < 0.0001) were associated with an elevated risk of childhood pneumonia; pneumonia was associated with an elevated risk of childhood asthma (1.96, 1.72-2.25; p < 0.0001), allergic rhinitis (1.60, 1.48-1.73; p < 0.0001) and wheezing (2.49, 2.25-2.75; p < 0.0001). CONCLUSIONS: Pneumonia is prevalent among preschool children in China, and it affects other childhood respiratory diseases. Although the prevalence of pneumonia in Chinese children shows a decreasing trend in 2019 compared to 2011, a well-established management system is still needed to further reduce the prevalence of pneumonia and reduce the burden of disease in children.

A real-world analysis of survival and cost-effectiveness of sintilimab plus bevacizumab biosimilar regimen in patients with advanced hepatocellular carcinoma.

PURPOSE: Programmed death-1 (PD-1) inhibitor sintilimab plus bevacizumab has been approved as the first-line treatment for patients with advanced hepatocellular carcinoma (aHCC). However, the clinical benefits of sintilimab plus bevacizumab in a real-world setting in China is insufficiently defined to date. This study aims to evaluate the efficacy and cost-effectiveness of sintilimab plus bevacizumab biosimilar in a real-word cohort of patients with aHCC from China. METHODS: We reviewed the clinical data of 112 consecutive patients with aHCC who received sintilimab plus bevacizumab as a first-line treatment in Chongqing University Cancer hospital between July, 2021 and December, 2022. Overall survival, progression-free survival, overall response rate, and adverse event rates were assessed based on the RECIST 1.1. The survival curves were grafted by Kaplan-Meier method. RESULTS: Sixty-eight patients with aHCC were included our study. Efficacy evaluation results showed that 8 patients were partial remission, 51 patients were stable and 9 patients showed progression disease. Median overall survival and progression-free survival were 344.00 (168.77-419.23) days and 238.00 (174.56-301.44) days, respectively. Adverse events occurred in 35 patients (51.5%), including 9 patients with grade ≥ 3. The life-year (LY) and quality-adjusted LY (QALY) were 1.97 and 2.92, respectively, with a cost of $35,018. CONCLUSION: Our data confirmed the promising efficacy, tolerable toxicity and cost-effectiveness in Chinese patients with aHCC who received sintilimab plus bevacizumab as the first-line therapy regimen in real-world practice.

Pan-cancer assessment of mutational landscape in intrinsically disordered hotspots reveals potential driver genes.

Large-scale cancer genome sequencing has enabled the catalogs of somatic mutations; however, the mutational impact on intrinsically disordered protein regions (IDRs) has not been systematically investigated to date. Here, we comprehensively characterized the mutational landscapes of IDRs and found that IDRs have higher mutation frequencies across diverse cancers. We thus developed a computational method, ROI-Driver, to identify putative driver genes enriching IDR and domain hotspots in cancer. Numerous well-known cancer-related oncogenes or tumor suppressors that play important roles in cancer signaling regulation, development and immune response were identified at a higher resolution. In particular, the incorporation of IDR structures helps in the identification of novel potential driver genes that play central roles in human protein-protein interaction networks. Interestingly, we found that the putative driver genes with IDR hotspots were significantly enriched with predicted phase separation propensities, suggesting that IDR mutations disrupt phase separation in key cellular pathways. We also identified an appreciable number of clinically relevant genes enriching IDR mutational hotspots that exhibited differential expression patterns and are associated with cancer patient survival. In summary, combinations of mutational effects on IDRs significantly increase the sensitivity of driver detection and are likely to open new therapeutic avenues for various cancers.

The developing trends and driving factors of environmental information disclosure in China.

Environmental Information Disclosure (EID) is a new tool for environmental governance in the era of big data and information. Based on the Pollution Information Disclosure Index (PITI) of 120 cities in China from 2003 to 2019, spatial data exploratory analysis and dynamic spatial panel model were adopted to analyze the spatial-temporal evolution characteristics and influencing factors of EID in China. The results show that (1) great progress of China's EID has been made in legislation and practice and its ways and channels are gradually becoming diversified, while it is accompanied by the problem of inadequate and unbalanced development; (2) EID shows the "superposition effect" promoted by previous accumulation has the "peer effect" of mutual imitation and learning and presents "demonstration effect", which shows significant agglomeration distribution pattern of spatial "club", while the spillover effect within the region is significant while the radiation effect between regions is weak. (3) In a dynamic process, cities with better economic development, firm performance, environmental performance and regulation, disclosure more environmental information, while the role of government competition and public participation needs further discussion. (4) Negative factors have a great influence during the economic crisis, while positive factors play a significant role in promoting the disclosure of environmental information during the economic expansion after crises. Cities in the developed regions (coastal, east and large cities) disclosure more than developing regions (inland, west, and small cities), and the positive factors are more likely to take effect.

Quantitative assessment of the association between AXIN2 rs2240308 polymorphism and cancer risk.

Axin2 is involved in the regulation of Wnt/ß-catenin pathway and implicated in cancer development and progression. The association between AXIN2 rs2240308 polymorphism and cancer risk has been examined in several case-control studies, but the conclusions were conflicting. Here we performed a meta-analysis to evaluate the role of rs2240308 in cancer risk. A total of 8 studies were included in this meta-analysis (1559 cancer cases and 1503 controls). The pooled odds ratios (OR) and the 95% confidence intervals (CIs) were assessed to evaluate the association of the AXIN2 rs2240308 polymorphism with a susceptibility to cancer. A significantly decreased overall cancer risk was observed in the homozygous (TT vs. CC), heterozygous (CT vs. CC), dominant (CT+TT vs. CC) and allelic (T vs. C) models (P < 0.005), rather than that in the recessive (TT vs. CT+CC) model (P = 0.092). AXIN2 polymorphism rs2240308 was also associated with decreased cancer risk under all five models in lung cancer. However, AXIN2 rs2240308 polymorphism was not associated with cancer risk under any above model in Turkish population and under homozygous, heterozygous, recessive models in Japanese population. These findings indicate that AXIN2 rs2240308 polymorphism significantly and race-specifically correlates with decreased cancer risk.

A synthetic peptide blocking the apolipoprotein E/beta-amyloid binding mitigates beta-amyloid toxicity and fibril formation in vitro and reduces beta-amyloid plaques in transgenic mice.

Alzheimer's disease (AD) is associated with accumulation of beta-amyloid (Abeta). A major genetic risk factor for sporadic AD is inheritance of the apolipoprotein (apo) E4 allele. ApoE can act as a pathological chaperone of Abeta, promoting its conformational transformation from soluble Abeta into toxic aggregates. We determined if blocking the apoE/Abeta interaction reduces Abeta load in transgenic (Tg) AD mice. The binding site of apoE on Abeta corresponds to residues 12 to 28. To block binding, we synthesized a peptide containing these residues, but substituted valine at position 18 to proline (Abeta12-28P). This changed the peptide's properties, making it non-fibrillogenic and non-toxic. Abeta12-28P competitively blocks binding of full-length Abeta to apoE (IC50 = 36.7 nmol). Furthermore, Abeta12-28P reduces Abeta fibrillogenesis in the presence of apoE, and Abeta/apoE toxicity in cell culture. Abeta12-28P is blood-brain barrier-permeable and in AD Tg mice inhibits Abeta deposition. Tg mice treated with Abeta12-28P for 1 month had a 63.3% reduction in Abeta load in the cortex (P = 0.0043) and a 59.5% (P = 0.0087) reduction in the hippocampus comparing to age-matched control Tg mice. Antibodies against Abeta were not detected in sera of treated mice; therefore the observed therapeutic effect of Abeta12-28P cannot be attributed to an antibody clearance response. Our experiments demonstrate that compounds blocking the interaction between Abeta and its pathological chaperones may be beneficial for treatment of beta-amyloid deposition in AD.

Determination of anion-exchange resin performance based on facile chloride-ion monitoring by FIA-spectrophotometry with applications to water treatment operation.

Based on a flow-injection spectrophotometry, an automatic analytical method for determination of ppb-level chloride-ion has been established. By use of this method, a novel FIA method for the determination of SBAER performance has also been developed. In this paper, the effects of concentration, dosage, and flow rate of the regenerant on BEC of SBAER were first investigated dynamically by the FIA method. In addition, the flow rate of the sample water and the temperature of the ion exchange resin were also examined. The optimum conditions were obtained: the volume of the regenerant (sodium hydroxide) was 50 mL (0.15 g resin), and its concentration was 3% (w/v); the volumetric flow rates of the regenerant and the sample water were 0.5 ml/min (4.3 m/h) and 1.5 ml/min (13 m/h), respectively. The exchanging temperature was 25 +/- 5 degrees C. The method is characterized by the use of a micro resin-column, shorter testing cycle, easy operation, and high reproducibility. The proposed method is approximately 30 times more efficient than the manual method, and it can be used for the exchange performance comparison of various SBAER.