Insurance-based compensation for adverse reactions following immunization in Wuxi City, Jiangsu Province from 2020 to 2022

ObjectiveTo assess the implementation of insurance-based compensation for adverse reactions following immunization in Wuxi City,Jiangsu Province.MethodsData on basic insurance and supplementary insurance for adverse reactions following immunization from 2020 to 2022 in Wuxi City was collected, and a descriptive epidemiological method was used to analyze the data.ResultsA total of 2 272 cases were compensated for adverse reactions following immunization,with a total compensation amount of 5.255 9 million yuan, and an average of 2.3 thousand yuan per case. Basic insurance accounted for 0.62% of the total cases and 10.72% of the total compensation amount, while supplementary insurance accounted for 99.43% of the total cases and 89.28% of the total compensation amount. Compensation amounts for disability and third-degree damage in basic insurance accounted for 63.18% and 88.71%, respectively, while fourth-degree and lower damage in supplementary insurance accounted for 96.52%. The compensation rate for supplementary insurance was higher than that for basic insurance. The highest number of compensated cases was in the 0‒ year age group, and vaccines included in the Expanded Program on Immunization (EPI) accounted for the majority of the cases and compensation amounts, with a percentage of 70.11% and 73.84%, respectively. For basic insurance, the largest number of compensated cases involved the Bacillus Calmette-Guérin (BCG) vaccine. For supplementary insurance, the top three compensated cases for EPI vaccines were the measles-mumps-rubella (MMR) vaccine, the hepatitis B (HepB) vaccine, and the acellular diphtheria-tetanus-pertussis (DTaP) vaccine. For non-EPI vaccines, the top three compensated cases were the 13 valent pneumococcal polysaccharide conjugate (PPCV13) vaccine, the acellular DPT-inactivated poliovirus-haemophilus influenzae type b combined vaccine (DPT-IPV/Hib), and enterovirus 71 (EV71) inactivated vaccine. In basic insurance, thrombocytopenic purpura and BCG local abscess both accounted for 21.43% of the cases, while in supplementary insurance, respiratory system diseases accounted for 77.47% of the cases. The time intervals from reporting to submission of compensation materials (<31 d) and from submission to payment of compensation (≤14 d) were 71.43% and 57.14% for basic insurance, and 90.22% and 86.23% for supplementary insurance, respectively.ConclusionThe commercial supplementary insurance for adverse reactions following immunization in Wuxi City has largely compensated for the limitations of basic insurance in terms of coverage and efficiency. It is recommended to further promote commercial compensation insurance for young children and strengthen the monitoring and regulation of commercial supplementary insurance compensation

Long Non-Coding RNA TUG1 Attenuates Insulin Resistance in Mice with Gestational Diabetes Mellitus via Regulation of the MicroRNA-328-3p/SREBP-2/ERK Axis

Background Long non-coding RNAs (lncRNAs) have been illustrated to contribute to the development of gestational diabetes mellitus (GDM). In the present study, we aimed to elucidate how lncRNA taurine upregulated gene 1 (TUG1) influences insulin resistance (IR) in a high-fat diet (HFD)-induced mouse model of GDM. Methods We initially developed a mouse model of HFD-induced GDM, from which islet tissues were collected for RNA and protein extraction. Interactions among lncRNA TUG1/microRNA (miR)-328-3p/sterol regulatory element binding protein 2 (SREBP-2) were assessed by dual-luciferase reporter assay. Fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), HOMA pancreatic β-cell function (HOMA-β), insulin sensitivity index for oral glucose tolerance tests (ISOGTT) and insulinogenic index (IGI) levels in mouse serum were measured through conducting gain- and loss-of-function experiments. Results Abundant expression of miR-328 and deficient expression of lncRNA TUG1 and SREBP-2 were characterized in the islet tissues of mice with HFD-induced GDM. LncRNA TUG1 competitively bound to miR-328-3p, which specifically targeted SREBP-2. Either depletion of miR-328-3p or restoration of lncRNA TUG1 and SREBP-2 reduced the FBG, FINS, HOMA-β, and HOMA-IR levels while increasing ISOGTT and IGI levels, promoting the expression of the extracellular signal-regulated kinase (ERK) signaling pathway-related genes, and inhibiting apoptosis of islet cells in GDM mice. Upregulation miR-328-3p reversed the alleviative effects of SREBP-2 and lncRNA TUG1 on IR. Conclusion Our study provides evidence that the lncRNA TUG1 may prevent IR following GDM through competitively binding to miR-328-3p and promoting the SREBP-2-mediated ERK signaling pathway inactivation

Genetic associations between gut microbiota and allergic rhinitis: an LDSC and MR analysis

BackgroundSeveral studies have suggested a potential link between allergic rhinitis (AR) and gut microbiota. In response, we conducted a meta-analysis of Linkage Disequilibrium Score Regression (LDSC) and Mendelian randomization (MR) to detect their genetic associations.MethodsSummary statistics for 211 gut microbiota taxa were gathered from the MiBioGen study, while data for AR were sourced from the Pan-UKB, the FinnGen, and the Genetic Epidemiology Research on Aging (GERA). The genetic correlation between gut microbiota and AR was assessed using LDSC. The principal estimate of causality was determined using the Inverse-Variance Weighted (IVW) method. To assess the robustness of these findings, sensitivity analyses were conducted employing methods such as the weighted median, MR-Egger, and MR-PRESSO. The summary effect estimates of LDSC, forward MR and reverse MR were combined using meta-analysis for AR from different data resources.ResultsOur study indicated a significant genetic correlation between genus Sellimonas (Rg = −0.64, p = 3.64 × 10−5, Adjust_P = 3.64 × 10−5) and AR, and a suggestive genetic correlation between seven bacterial taxa and AR. Moreover, the forward MR analysis identified genus Gordonibacter, genus Coprococcus2, genus LachnospiraceaeUCG010, genus Methanobrevibacter, and family Victivallaceae as being suggestively associated with an increased risk of AR. The reverse MR analysis indicated that AR was suggestively linked to an increased risk for genus Coprococcus2 and genus RuminococcaceaeUCG011.ConclusionOur findings indicate a causal relationship between specific gut microbiomes and AR. This enhances our understanding of the gut microbiota’s contribution to the pathophysiology of AR and lays the groundwork for innovative approaches and theoretical models for future prevention and treatment strategies in this patient population

Genetic associations between gut microbiota and type 2 diabetes mediated by plasma metabolites: a Mendelian randomization study

BackgroundNumerous research studies have indicated a possible association between type 2 diabetes (T2DM) and gut microbiota. To explore specific metabolic pathways connecting gut microbiota and T2DM, we employed Mendelian randomization (MR) and linkage disequilibrium score regression (LDSC) techniques.MethodsThis research utilized data from genome-wide association studies (GWAS) that are publicly accessible. We evaluated the genetic correlation between gut microbiota and T2DM using LDSC. Causality was primarily determined through the inverse variance weighted (IVW) method. To verify the robustness of our results, we conducted sensitivity analyses using several approaches, including the weighted median, MR-Egger, and MR-PRESSO. We integrated summary effect estimates from LDSC, along with forward and reverse MR, into a meta-analysis for T2DM using various data sources. Additionally, mediation analysis was performed to explore the impact of plasma metabolites on the relationship between gut microbiota and T2DM.ResultsOur study indicated a significant genetic correlation between genus RuminococcaceaeUCG005 (Rg = −0.26, Rg_P = 2.07×10−4) and T2DM. Moreover, the forward MR analysis identified genus RuminococcaceaeUCG010 (OR = 0.857, 95% CI 0.795, 0.924; P = 6.33×10−5) and order Clostridiales (OR = 0.936, 95% CI 0.878, 0.997; P = 0.039) as being significantly associated with a decreased risk of T2DM. The analysis also highlighted several plasma metabolites as significant mediators in these relationships, with metabolites like octadecadienedioate (C18:2-DC) and branched chain 14:0 dicarboxylic acid being notably involved.ConclusionThe findings demonstrate a significant impact of gut microbiota on T2DM via plasma metabolites, suggesting potential metabolic pathways for therapeutic targeting. This study enhances our understanding of the microbiota’s role in T2DM pathogenesis and supports the development of microbiota-based interventions

Importance of Incorporating Protein Flexibility in Molecule Modeling: A Theoretical Study on Type I1/2 NIK Inhibitors

NF-κB inducing kinase (NIK), which is considered as the central component of the non-canonical NF-κB pathway, has been proved to be an important target for the regulation of the immune system. In the past few years, NIK inhibitors with various scaffolds have been successively reported, among which type I1/2 inhibitors that can not only bind in the ATP-binding pocket at the DFG-in state but also extend into an additional back pocket, make up the largest proportion of the NIK inhibitors, and are worthy of more attention. In this study, an integration protocol that combines molecule docking, MD simulations, ensemble docking, MM/GB(PB)SA binding free energy calculations, and decomposition was employed to understand the binding mechanism of 21 tricyclic type I1/2 NIK inhibitors. It is found that the docking accuracy is largely dependent on the selection of docking protocols as well as the crystal structures. The predictions given by the ensemble docking based on multiple receptor conformations (MRCs) and the MM/GB(PB)SA calculations based on MD simulations showed higher linear correlations with the experimental data than those given by conventional rigid receptor docking (RRD) methods (Glide, GOLD, and Autodock Vina), highlighting the importance of incorporating protein flexibility in predicting protein–ligand interactions. Further analysis based on MM/GBSA demonstrates that the hydrophobic interactions play the most essential role in the ligand binding to NIK, and the polar interactions also make an important contribution to the NIK-ligand recognition. A deeper comparison of several pairs of representative derivatives reveals that the hydrophobic interactions are vitally important in the structural optimization of analogs as well. Besides, the H-bond interactions with some key residues and the large desolvation effect in the back pocket devote to the affinity distinction. It is expected that our study could provide valuable insights into the design of novel and potent type I1/2 NIK inhibitors

Targeted proteomics-determined multi-biomarker profiles developed classifier for prognosis and immunotherapy responses of advanced cervical cancer

BackgroundCervical cancer (CC) poses a global health challenge, with a particularly poor prognosis in cases of recurrence, metastasis, or advanced stages. A single biomarker is inadequate to predict CC prognosis or identify CC patients likely to benefit from immunotherapy, presumably owing to tumor complexity and heterogeneity.MethodsUsing advanced Olink proteomics, we analyzed 92 oncology-related proteins in plasma from CC patients receiving immunotherapy, based upon the comparison of protein expression levels of pre-therapy with those of therapy-Cycle 6 in the partial response (PR) group and progressive disease (PD) group, respectively.Results55 proteins were identified to exhibit differential expression trends across pre-therapy and post-therapy in both PR and PD groups. Enriched GO terms and KEGG pathways were associated with vital oncological and immunological processes. A logistic regression model, using 5 proteins (ITGB5, TGF-α, TLR3, WIF-1, and ERBB3) with highest AUC values, demonstrated good predictive performance for prognosis of CC patients undergoing immunotherapy and showed potential across different cancer types. The effectiveness of these proteins in prognosis prediction was further validated using TCGA-CESC datasets. A negative correlation and previously unidentified roles of WIF-1 in CC immunotherapy was also first determined.ConclusionOur findings reveal multi-biomarker profiles effectively predicting CC prognosis and identifying patients benefitting most from immunotherapy, especially for those with limited treatment options and traditionally poor prognosis, paving the way for personalized immunotherapeutic treatments and improved clinical strategies

A novel transcription factor-based signature to predict prognosis and therapeutic response of hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is one of the most common aggressive malignancies with increasing incidence worldwide. The oncogenic roles of transcription factors (TFs) were increasingly recognized in various cancers. This study aimed to develop a predicting signature based on TFs for the prognosis and treatment of HCC.Methods: Differentially expressed TFs were screened from data in the TCGA-LIHC and ICGC-LIRI-JP cohorts. Univariate and multivariate Cox regression analyses were applied to establish a TF-based prognostic signature. The receiver operating characteristic (ROC) curve was used to assess the predictive efficacy of the signature. Subsequently, correlations of the risk model with clinical features and treatment response in HCC were also analyzed. The TF target genes underwent Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, followed by protein-protein-interaction (PPI) analysis.Results: A total of 25 differentially expressed TFs were screened, 16 of which were related to the prognosis of HCC in the TCGA-LIHC cohort. A 2-TF risk signature, comprising high mobility group AT-hook protein 1 (HMGA1) and MAF BZIP transcription factor G (MAFG), was constructed and validated to negatively related to the overall survival (OS) of HCC. The ROC curve showed good predictive efficiencies of the risk score regarding 1-year, 2-year and 3-year OS (mostly AUC &gt;0.60). Additionally, the risk score independently predicted OS for HCC patients both in the training cohort of TCGA-LIHC dataset (HR = 2.498, p = 0.007) and in the testing cohort of ICGC-LIRI-JP dataset (HR = 5.411, p &lt; 0.001). The risk score was also positively correlated to progressive characteristics regarding tumor grade, TNM stage and tumor invasion. Patients with a high-risk score were more resistant to transarterial chemoembolization (TACE) treatment and agents of lapatinib and erlotinib, but sensitive to chemotherapeutics. Further enrichment and PPI analyses demonstrated that the 2-TF signature distinguished tumors into 2 clusters with proliferative and metabolic features, with the hub genes belonging to the former cluster.Conclusion: Our study identified a 2-TF prognostic signature that indicated tumor heterogeneity with different clinical features and treatment preference, which help optimal therapeutic strategy and improved survival for HCC patients

Investigation of energetic ion losses induced by long-lived saturated internal mode with energetic particle diagnostics in the HL-2A tokamak

ORCID　0000-0002-7547-701XSeveral sets of energetic particle diagnostics, including a set of neutron flux monitoring systems, a solid-state neutral particle analyzer and a fast ion loss probe (FILP), have been used to investigate the energetic ion losses induced by the long-lived saturated internal mode (LLM) in the HL-2A tokamak. Clear experimental evidence for different levels of energetic ion losses induced by LLM, sawtooth and minor disruption has been observed. A numerical calculation for the evolution of neutron emissions was carried out with the FBURN code, and it shows that the neutron emission drop rate linearly increases with the LLM amplitude and no threshold perturbation amplitude exists, illustrating that the loss mechanism for LLM induced energetic ion loss is dominantly convective. In addition, measurement results of the FILP demonstrate that LLM tends to expel energetic ions with relatively low energy ($E \lt 27\,$keV) and high pitch angle ($\theta\gt60^{\circ}$), and can suppress the prompt loss of energetic ions with high energy and low pitch angle to a certain degree. Furthermore, the physical process for LLM induced energetic ion loss can be explained by orbit calculations, which show that LLM induced lost energetic ions will transport from center to peripheral region first, and then get lost out of plasma. The experimental observations are successfully reproduced by calculations using the ORBIT code combined with both the NUBEAM code and the MARS-K code. The paper clearly describes the whole physical process of LLM induced energetic ion loss for the first time in the HL-2A tokamak.journal articl