Psychological needs and social comparison: a dual analysis of the life satisfaction of local workers with agricultural hukou.

BACKGROUND: Based on their place of employment, workers with agricultural hukou (WAH) are categorized into local workers with agricultural hukou (LWAH) and migrant workers with agricultural hukou (MWAH). Research shows that although LWAH often find themselves at a disadvantage in terms of labour income and access to public services, the significant growth of this group in recent years has drawn attention to their choice of workplace and the factors influencing it. Guided by the theories of self-determination and social comparison, this study aims to explore the impact of the differences between LWAH and MWAH in psychological needs and social comparisons on life satisfaction, as well as the underlying mechanisms. METHODS: This study utilizes data from the China Family Panel Studies (CFPS) from 2014 to 2020, employing a two-way fixed effects model to investigate the differences in life satisfaction between 1,976 LWAH and MWAH. Additionally, propensity score matching (PSM) is used to conduct regression analysis on the matched sample, providing a more accurate comparison of life satisfaction between LWAH and MWAH under similar individual characteristics. Finally, the study further examines the mediating effects of perceived social status and job satisfaction and analyses the differences in life satisfaction between LWAH and MWAH across dimensions such as generation, region, and work conditions. RESULTS: The baseline regression results indicate that LWAH have significantly higher life satisfaction compared to MWAH, and this finding is robust to various tests. Mediation analysis reveals that perceived social status plays a mediating role in the difference in life satisfaction between LWAH and MWAH, while job satisfaction does not have a significant mediating effect. Heterogeneity analysis further shows that intergenerational, regional, and work condition differences have varying impacts on the life satisfaction of two groups. CONCLUSIONS: This study provides important insights into understanding the workplace choices and quality of life of Chinese workers with agricultural hukou. Finally, to effectively promote situ urbanization processes, local governments need to prioritize enhancing workers with agricultural hukou (WAH)'s autonomy, sense of competence, and social status, thereby improving their perceived social status in society and attracting more labourers to return to their hometowns for work and entrepreneurship.

Use of a PK/PD Model to Select Cetagliptin Dosages for Patients with Type 2 Diabetes in Phase 3 Trials.

BACKGROUND: Cetagliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor developed for the treatment of patients with type 2 diabetes (T2D). Several phase 1 studies have been conducted in China. Modelling and simulation were used to obtain cetagliptin dose for phase 3 trials in T2D patients. METHODS: A pharmacokinetic (PK)/pharmacodynamic (PD) model and model-based analysis of the relationship between hemoglobin A1c (HbA1c) and dosage was explored to guide dose selection of cetagliptin for phase 3 trials. The PK/PD data were derived from four phase 1 clinical studies, and sitagliptin 100 mg was employed as a positive control in studies 1, 3, and 4. RESULTS: The PK profiles of cetagliptin were well described by a two-compartment model with first-order absorption, saturated efflux, and first-order elimination. The final PD model was a sigmoid maximum inhibitory efficacy (Emax) model with the Hill coefficient. The final model accurately captured cetagliptin PK/PD, demonstrated by goodness-of-fit plots. Based on weighted average inhibition (WAI), the relationship between HbA1c and dose was well displayed. Cetagliptin 50 mg once daily or above as monotherapy or as add-on therapy appeared more effective in HbA1c reduction than sitagliptin 100 mg. Cetagliptin 50 mg or 100 mg once daily was selected as the dose for phase 3 trials of cetagliptin in T2D patients. CONCLUSIONS: The PK/PD model supports dose selection of cetagliptin for phase 3 trials. A model­informed approach can be used to replace a dose-finding trial and accelerate cetagliptin's development.

Safety and effectiveness of baloxavir marboxil and oseltamivir for influenza in children: a real-world retrospective study in China.

Objectives: To evaluate the safety and effectiveness of baloxavir marboxil (baloxavir) and oseltamivir in pediatric influenza patients in China. Methods: Patients filling a prescription for baloxavir or oseltamivir within 48 h following an influenza-related outpatient visit were identified in Children's Hospital of Fudan University in China between March 2023 and December 2023. Outcomes were assessed after antiviral treatment and included the incidence of adverse reactions and the duration of fever and other flu symptoms. Results: A total of 1430 patients infected with influenza A were collected and 865 patients (baloxavir: n = 420; oseltamivir: n = 445) finally included. The incidence of adverse reactions of nausea and vomiting was significantly different between the baloxavir group (2.38%) and the oseltamivir group (12.13%) [P < 0.001, OR = 4.2526, 95%CI (2.0549, 9.6080)]. No differences in other adverse reactions were observed between the two groups. The mean duration of fever in baloxavir group (1.43d) was significantly shorter than that in oseltamivir group (2.31d) [P < 0.001, 95%CI (0.7815, 0.9917)]. There were no differences in the mean duration of nasal congestion and runny nose, sore throat, cough, and muscle soreness between two groups. Conclusions: The incidence of nausea and vomiting is lower with baloxavir compared to oseltamivir, and the duration for complete fever reduction is shorter with baloxavir than with oseltamivir. The results indicate that baloxavir is well tolerated and effective in Chinese children.

Population pharmacokinetics of oxcarbazepine active metabolite in Chinese paediatric patients with epilepsy: Model-based dose optimization.

The pharmacological activity of oxcarbazepine (OXC) is primarily exerted through its active 10-monohydroxy metabolite (MHD). Nonetheless, there is limited pharmacokinetic information available regarding paediatric patients with epilepsy treated with OXC, especially in infants and toddlers. Concurrently, this drug exhibits substantial variability in pharmacokinetics and therapeutic response across different individuals. We aimed to develop a model to quantitatively investigate factors that affect MHD pharmacokinetics to formulate a dosage guideline for OXC in Chinese paediatric patients. A total of 297 MHD trough concentrations were obtained from 287 epileptic children. Six body weight (BW)-based allometric models were used for population pharmacokinetic modelling, while investigating the impact of other covariates on the apparent clearance. The one-compartment model and age cut-off model for the apparent clearance (CL/F) were established to describe the pharmacokinetics of MHD. The probability to obtain target trough concentration ranges (TTCRs) of MHD between 3 and 35 mg/L was determined by Monte Carlo simulations for doses ranging from 8 to 90 mg/kg/day. A new dose optimization strategy combining the dosage guidelines and Bayesian method provides a tailored approach for Chinese paediatric epileptic patients based on their individual BW and desired TTCRs of MHD, and also supports current dose recommendations, with the exception of children weighing ≤5 kg.

Efficacy and safety of cetagliptin as monotherapy in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled phase 3 trial.

AIM: To assess the efficacy and safety of the dipeptidyl peptidase-4 inhibitor, cetagliptin, as monotherapy in Chinese patients with type 2 diabetes (T2D) and inadequate glycaemic control. MATERIALS AND METHODS: In total, 504 eligible patients with T2D were enrolled and randomized to cetagliptin 50 mg once daily, cetagliptin 100 mg once daily or placebo at a ratio of 2:2:1 for 24 weeks of double-blind treatment, then all patients received cetagliptin 100 mg once daily for 28 weeks of open-label treatment. The primary efficacy endpoint was the change in HbA1c level from baseline at week 24. RESULTS: After 24 weeks, HbA1c from baseline was significantly reduced with cetagliptin 50 mg (-1.08%) and cetagliptin 100 mg (-1.07%) compared with placebo (-0.35%). The placebo-subtracted HbA1c reduction was -0.72% with cetagliptin 50 mg and 100 mg. Patients with a baseline HbA1c of 8.5% or higher had a greater HbA1c reduction with cetagliptin than those patients with a baseline HbA1c of less than 8.5%. Both doses studied led to a significantly higher proportion of patients (42.3% with 100 mg and 45.0% with 50 mg) achieving an HbA1c of less than 7.0% compared with placebo (12.9%). Cetagliptin also significantly lowered fasting plasma glucose and 2-hour postmeal plasma glucose relative to placebo. The incidence of adverse experiences was similar between cetagliptin and placebo. No drug-related hypoglycaemia was reported. CONCLUSIONS: Cetagliptin monotherapy was effective and well tolerated in Chinese patients with T2D who had inadequate glycaemic control on exercise and diet.

A randomized, double-blind, placebo controlled, phase 3 trial to evaluate the efficacy and safety of cetagliptin added to ongoing metformin therapy in patients with uncontrolled type 2 diabetes with metformin monotherapy.

AIM: This trial was designed to assess the efficacy and safety of cetagliptin added to metformin in Chinese patients with type 2 diabetes who had inadequate glycaemic control with metformin monotherapy. METHODS: In total, 446 patients with type 2 diabetes on metformin monotherapy were randomized to receive the addition of once-daily cetagliptin 100 mg, cetagliptin 50 mg and placebo in a 2:2:1 ratio for 24-week double-blind treatment. At week 24, patients initially randomized to cetagliptin 50 mg and placebo were switched to cetagliptin 100 mg for 28 weeks open-label treatment. The primary endpoint was the change in haemoglobin A1c (HbA1c) from baseline, and the efficacy analyses were based on an all-patients-treated population using an analysis of co-variance. RESULTS: After 24 weeks, both add-on therapies led to greater glycaemic control. Reductions in HbA1c from baseline were -1.17 ± 0.794%, -1.23 ± 0.896% in cetagliptin 100 mg and 50 mg plus metformin group, respectively. No difference was observed between the cetagliptin 100 mg and 50 mg plus metformin group. Patients with higher baseline HbA1c levels (≥8.5%) experienced greater reductions in HbA1c. A significantly greater proportion of patients achieved an HbA1c <7.0% with cetagliptin 100 mg (49.4%) and cetagliptin 50 mg (51.1%) plus metformin than metformin monotherapy (14.4%). Both combination therapies also improved the homeostasis model assessment ß-function index and decreased systolic blood pressure. There was no increased risk of adverse effects with combination therapy, and both combination therapies were generally well tolerated. CONCLUSIONS: The addition of cetagliptin once daily to metformin was more efficacious and well tolerated than metformin monotherapy in Chinese patients with type 2 diabetes who had inadequate glycaemic control with metformin monotherapy.

Overexpression of Homer1b/c induces valproic acid resistance in epilepsy.

AIMS: Resistance to valproic acid (VPA) is a major challenge for epilepsy treatment. We aimed to explore the mechanism underlying this resistance. METHODS: Pentylenetetrazol-induced chronic epileptic rats were administered VPA (250 mg/Kg) for 14 days; rats with controlled seizure stages (seizure score14th-before ≤0) and latent time (latent time14th-before ≥0) were considered VPA-responsive, while the others were considered nonresponsive. Differentially expressed genes (DEGs) between the VPA-responsive and nonresponsive rat hippocampus transcriptomes were identified, and their functions were evaluated. The roles of postsynaptic density (PSD) and Homer1 were also determined. Furthermore, a subtype of Homer1 (Homer1b/c) was overexpressed or silenced in HT22 cells to determine its effect on VPA efficacy. Moreover, the membrane levels of mGluR1/5 directly bound to Homer1b/c were assessed. RESULTS: Overall, 264 DEGs commonly enriched in the PSD between VPA-responsive and nonresponsive rats. Among them, Homer1 was more highly expressed in the hippocampus of nonresponses compared to that of responses. Overexpression of Homer1b/c interrupted VPA efficacy by increasing reactive oxygen species production, lactate dehydrogenase release, and calcium content. Furthermore, it induced the overexpression of mGluR1 and mGluR5. CONCLUSION: Overexpression of Homer1b/c influenced VPA efficacy, revealing it could be a target to improve the efficacy of this treatment.

A novel drug selection decision support model based on real-world medical data by the hybrid entropic weight TOPSIS method.

BACKGROUND: The medicine selection method is a critical and challenging issue in medical insurance decision-making. OBJECTIVES: This study proposed a real-world data-based multi-criteria decision analysis (MCDA) model with a hybrid entropic weight Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) algorithms to select satisfactory drugs. METHODS: The evaluation index includes two levels: primary criteria and sub-criteria. Firstly, we proposed six primary criteria to form the value health framework. The primary criteria's weights were derived from the policymakers' questionnaire. Meanwhile, clinically relevant sub-criteria were derived from high-quality (screened by GRADE scores) clinical-research literature. Their weights are determined by the entropy weight (EW) algorithm. Secondly, we split the primary criteria into six mini-EW-TOPSIS models. Then, we obtained six ideal closeness degree scores (ICDS) for each candidate drug. Thirdly, we get the total utility score by linear weighting the ICDS. The higher the utility score, the higher the ranking. RESULTS: A national multicenter real-world case study of the ranking of four generic antibiotics validated the proposed model. This model is verified by comparative experiments and sensitivity analysis. The whole ranking model was consistent and reliable. Based on these results, medical policymakers can intuitively and easily understand the characteristics of each drug to facilitate follow-up drug policy-making. CONCLUSION: The ranking algorithm combines the objective characteristics of medicine and policy makers' opinions, which can improve the applicability of the results. This model can help decision-makers, clinicians, and related researchers better understand the drug assessment process.

Inspiration to mRNA-based COVID-19 vaccination: Serious adverse case reports with hepatitis B vaccine in real-world.

Objectives: The hepatitis B vaccine comprises hepatitis B surface antigen (HBsAg) produced by transgenic yeast cells. There are few serious adverse events (SAE) reports after Hepatitis B vaccination. Methods: The authors searched the Chinese legal documents database for all SAE with Hepatitis B vaccination from January 2010 to January 2022. Results: All seven patients received yeast-derived recombinant hepatitis B vaccine. Three cases of myocarditis (death), 2 cases of interstitial pneumonia (death), and 2 cases of encephalitis. The mean time of onset of SAE was 8.3 ± 4.3 h after vaccination. Conclusion: The mechanism of vaccine-induced myocarditis may come from immune protein reactions. Based on the experience of Hepatitis B vaccine adverse events, we present new insights into the mechanism of myocarditis caused by the COVID-19 vaccine.

Molecular Mechanism of YuPingFeng in the Treatment of Asthma Based on Network Pharmacology and Molecular Docking Technology.

Objective: To explore the molecular targets and mechanism of YuPingFeng (YPF) for the treatment of asthma by using network pharmacology and molecular docking. Methods: The potential active ingredients and relevant targets of YPF were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Asthma-related gene targets were retrieved from GeneCards, OMIM, DrugBank, PharmGKB, and TTD databases. The protein-protein (PPI) network between YPF and asthma common targets was constructed by SRING online database and Cytoscape software. GO and KEGG analyses were performed to explore the complicated molecular biological processes and potential pathways. Finally, a molecular docking approach was carried out to verify the results. Results: We obtained 100 potential targets of the 35 active ingredients in YPF and 1610 asthma-related targets. 60 YPF-asthma common targets were selected to perform PPI analysis. Seven core genes were screened based on two topological calculation methods. GO and KEGG results showed that the main pathways of YPF in treating asthma include TNF signaling pathway and PI3K-Akt signaling pathway. Finally, the molecular docking results indicated that the key ingredients of YPF had a good affinity with the relevant core genes. Conclusion: This study reflects the multicomponent, multitarget, and multipathway characteristics of YPF in treating asthma, providing a theoretical and scientific basis for the intervention of asthma by traditional Chinese medicine YPF.

Profiles of Microbial Community and Antibiotic Resistome in Wild Tick Species.

Infections caused by antibiotic-resistant pathogens pose high risks to human and animal health worldwide. In recent years, the environment and wildlife as major sources and reservoirs of antibiotic resistance genes (ARGs) are being increasingly investigated. There have been many reports on bacterial community in ticks, but little is known about ARGs they carry, and the correlation between bacterial and ARGs in wild ticks also remains unknown. Here, the profiles of microbial community and antibiotic resistome in wild tick species were investigated using high-throughput 16S rRNA sequencing and smart chip-based high-throughput quantitative PCR approach (HT-qPCR), respectively. We found that bacterial composition in wild tick species is variable; the sequenced reads from all samples were assigned to 37 different phyla at the phylum level. The dominant phylum was Proteobacteria, which accounted for 75.60 ± 10.34%, followed by Bacteroidetes accounting for 13.78 ± 11.68% of the total bacterial community. In total, 100 different ARGs across 12 antibiotic classes and 20 mobile genetic elements (MGEs) were identified by HT-qPCR, and among them aminoglycosides, multidrug, macrolide-clinolamide-streptogramin B, and tetracycline resistance genes were the dominant ARG types. Co-occurrence patterns revealed by network analysis showed that eight bacterial genera may serve as the potential hosts for different ARGs. For the first time, this study provides comprehensive overview of the diversity and abundance of ARGs in wild ticks and highlights the possible role of wild ticks as ARG disseminators into the environment and vertebrate hosts, with implications for human and animal health. IMPORTANCE The emergence of antibiotic-resistant bacteria poses serious threat to the public health around the world. Ticks are obligate hematophagous ectoparasites, surviving via feeding on the blood of various animal hosts. Although some previous studies have confirmed wild ticks carried various bacterial community, the role of wild ticks in the antibiotic resistance remains unknown. Here, identification of microbial community and antibiotic resistome in wild tick species revealed that wild ticks are the reservoir, postulated potential spreaders of antibiotic resistance. Our findings highlight the contribution of wild ticks to the maintenance and dissemination of ARGs, and the associated health risks.

Corrigendum: Anti-Tumoral Effect and Action Mechanism of Exosomes Derived From Toxoplasma gondii-Infected Dendritic Cells in Mice Colorectal Cancer.

[This corrects the article DOI: 10.3389/fonc.2022.870528.].

Eukaryotic expression and immunogenicity of Ancylostoma ceylanicum calreticulin.

Ancylostoma ceylanicum is a zoonotic soil-derived nematode that parasitizes human and animal intestines, causing malnutrition and iron-deficiency anemia. Calreticulin is a multifunctional protein involved in all stages of parasitic infection. Studies have found that parasites can secret calreticulin to regulate the host's immune response. To explore the immunogenicity of the eukaryotic expression plasmid of Ancylostoma ceylanicum calreticulin (Ace-CRT), we constructed a recombinant Ace-CRT eukaryotic expression plasmid (pEGFP-N3-Ace-CRT). Successful expression of the target protein in Human Embryonic Kidney (HEK) 293 T cells was confirmed by indirect immunofluorescence and Western blot analysis. BALB/c mice were immunized with pEGFP-N3-Ace-CRT plasmid. Measuring IgG antibody levels in immunized mice sera by ELISA showed that the recombinant plasmid stimulated IgG antibody production in mice. Spleen lymphocytes were collected from vaccinated mice to determine the proportion of T cell subsets and the expression levels of cytokines. Flow cytometry revealed that the percentage of CD3 + CD4+ and CD3 + CD8+ T cells in mice spleen in the immunization group was significantly higher than that in the control group. Recombinant plasmid immunization increased IL-4, IL-10, IL-12, and IL-13 expression while decreasing IL-5, IL-6, and INF-γ in mice spleens. These results indicate that the eukaryotic plasmid constructed in this study had good immunogenicity and mainly induced a T helper 2 response in the host, laying a foundation for screening candidate molecules for anti-hookworm vaccines.

First vaccination after birth: serious adverse events of Bacillus Calmette-Guérin (BCG) in real-world.

The Bacillus Calmette-Guérin (BCG) vaccine is a free vaccine in China, and more than 300 million newborns have been vaccinated. Inevitably, the BCG vaccine will have some rare adverse events on the first day of life (24 hours after birth), but related reports are extremely rare. In this commentary, the authors searched the Chinese legal documents database for documents related to serious adverse events caused by BCG from January 2010 to January 2022. Fourteen pediatric cases were identified, including 7 preterm infants and 7 full-term infants. The events included 4 cases of interstitial pneumonia, 3 cases of lymphadenitis, 3 cases of septicemia, 1 case of myocarditis, 1 case of muscle atrophy, 1 case of epilepsy, and 1 case of disseminated BCG vaccine. The mortality rate of preterm infants was 100% and that of full-term infants was 28.6% (2/7). All deaths occurred within one day. The BCG vaccine has good safety for the vast majority of newborns.

To our knowledge, we present the largest case series of BCG vaccine-induced serious adverse events in neonates.The BCG vaccine has good safety for the vast majority of newborns.The incidence of serious adverse events with BCG vaccine may be as low as eight per million.