Inflammatory bowel disease is causally related to irritable bowel syndrome: a bidirectional two-sample Mendelian randomization study.

Introduction: Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are lifelong digestive diseases that severely impact patients' quality of life. The existence of a causal association between IBS and IBD remains unclear. This study aimed to determine the direction of causality between IBD and IBS by quantifying their genome-wide genetic associations and performing bidirectional two-sample Mendelian randomization (MR) analyses. Methods: Genome-wide association studies (GWAS) among a predominantly European patient cohort identified independent genetic variants associated with IBS and IBD. Two separate databases (a large GWAS meta-analysis and the FinnGen cohort) for both IBS and IBD were consulted to retrieve statistics on instrument-outcome associations. MR analyses included inverse-variance-weighted, weighted-median, MR-Egger regression, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods, and sensitivity analyses were performed. The MR analyses were carried out for each outcome data, followed by a fixed-effect meta-analysis. Results: Genetically predicted IBD was associated with an increased risk of IBS. Odds ratios (95% confidence intervals) for samples of 211,551 (17,302 individuals with IBD), 192,789 (7,476 Crohn's disease cases), and 201,143 (10,293 ulcerative colitis cases) individuals were 1.20 (1.00, 1.04), 1.02 (1.01, 1.03), and 1.01 (0.99, 1.03), respectively. After outlier correction using MR-PRESSO, the odds ratio for ulcerative colitis was 1.03 (1.02, 1.05) (p = 0.001). However, an association between genetically influenced IBS and IBD was not identified. Discussion: This study confirms that IBD is causally related to IBS, which may interfere with the diagnosis and treatment of both diseases.

{[In2S7]8-}∞ Chain and Isolated HgS4 Planar Unit Constructed One-Dimensional Pentanary Sulfide K2Ba7HgIn4S16 Exhibiting Nonlinear-Optical Activity.

Hg-based chalcogenides possess diverse structures, large nonlinear-optical (NLO) responses, and suitable birefringences, making them potentially suitable for numerous crucial criteria of practical application as infrared (IR) NLO crystals. Here, a new pentanary Hg-based sulfide K2Ba7HgIn4S16 has been discovered by a high-temperature solid-state method. It crystallizes in the orthorhombic P21212 space group, and its one-dimensional structure is constructed by {[In2S7]8-}∞ chains and isolated [HgS4]6- planar quadrilateral units located bewteeen the chains, representing a novel type of chalcogenide. K2Ba7HgIn4S16 exhibits a moderate NLO effect of 0.5 × AGS at 2.1 µm and a high laser-induced damage threshold of ∼5.8 × AGS, as well as a band gap of 2.98 eV, demonstrating that K2Ba7HgIn4S16 is a potential IR NLO material. This work enriches the structural chemistry of chalcogenides and the family of Hg-based IR NLO chalcogenides.

Theory of mobility of inhomogeneous-polymer-grafted particles.

We develop a theory for the motion of a particle grafted with inhomogeneous bead-spring Rouse chains via the generalized Langevin equation (GLE), where individual grafted polymers are allowed to take different bead friction coefficients, spring constants, and chain lengths. An exact solution of the memory kernel K(t) is obtained for the particle in the time (t) domain in the GLE, which depends only on the relaxation of the grafted chains. The t-dependent mean square displacement g(t) of the polymer-grafted particle is then derived as a function of the friction coefficient γ0 of the bare particle and K(t). Our theory offers a direct way to quantify the contributions of the grafted chain relaxation to the mobility of the particle in terms of K(t). This powerful feature enables us to clarify the effect on g(t) of dynamical coupling between the particle and grafted chains, leading to the identification of a relaxation time of fundamental importance in polymer-grafted particles, namely, the particle relaxation time. This timescale quantifies the competition between the contributions of the solvent and grafted chains to the friction of the grafted particle and separates g(t) into the particle- and chain-dominated regimes. The monomer relaxation time and the grafted chain relaxation time further divide the chain-dominated regime of g(t) into subdiffusive and diffusive regimes. Analysis of the asymptotic behaviors of K(t) and g(t) provides a clear physical picture of the mobility of the particle in different dynamical regimes, shedding light on the complex dynamics of polymer-grafted particles.

Strategy insight: Mechanical properties of biomaterials' influence on hydrogel-mesenchymal stromal cell combination for osteoarthritis therapy.

Osteoarthritis (OA) is a kind of degenerative joint disease usually found in older adults and those who have received meniscal surgery, bringing great suffering to a number of patients worldwide. One of the major pathological features of OA is retrograde changes in the articular cartilage. Mesenchymal stromal cells (MSCs) can differentiate into chondrocytes and promote cartilage regeneration, thus having great potential for the treatment of osteoarthritis. However, improving the therapeutic effect of MSCs in the joint cavity is still an open problem. Hydrogel made of different biomaterials has been recognized as an ideal carrier for MSCs in recent years. This review focuses on the influence of the mechanical properties of hydrogels on the efficacy of MSCs in OA treatment and compares artificial materials with articular cartilage, hoping to provide a reference for further development of modified hydrogels to improve the therapeutic effect of MSCs.

Automatic optimization of miniaturized bound states in the continuum cavity.

Bound states in the continuum (BICs) provide, what we believe to be, a novel and efficient way for light trapping. However, using BICs to confine the light into a three-dimensional compact volume remains a challenging task, since the energy leakage at the lateral boundaries dominates the cavity loss when its footprint shrinks to considerably small, and hence, sophisticated boundary designs turn out to be inevitable. Conventional design methods fail in solving the lateral boundary problem because a large number of degree-of-freedoms (DOFs) are involved. Here, we propose a fully automatic optimization method to promote the performance of lateral confinement for a miniaturized BIC cavity. Briefly, we combine a random parameter adjustment process with a convolutional neural network (CNN), to automatically predict the optimal boundary design in the parameter space that contains a number of DOFs. As a result, the quality factor that is accounted for lateral leakage increases from 4.32 × 104 in the baseline design to 6.32 × 105 in the optimized design. This work confirms the effectiveness of using CNNs for photonic optimization and will motivate the development of compact optical cavities for on-chip lasers, OLEDs, and sensor arrays.

Chemical constituents of Wikstroemia alternifolia and their neuroprotective activities.

Phytochemical investigation on the plant of Wikstroemia alternifolia led to the isolation of 26 compounds including two new ones, wikstralternifols A and B (1 and 7). Their structures including the absolute configuration were elucidated by spectroscopic data together with analysis of experimental and calculated ECD data. All compounds were isolated from this plant for the first time, and their main structural types were lignans, sesquiterpenoids, and flavonoids. In the sodium nitroprusside-induced rat pheochromocytoma PC-12 cell model, the neuroprotective activities of the selected sesquiterpenoids (1 and 4) and lignans (7 - 14) were screened at the concentration of 10 µM, and 7 - 14 displayed better activities than the positive control edaravone.

Advances in Drug Therapy for Gastrointestinal Stromal Tumour.

Gastrointestinal stromal tumour (GIST) is a common gastrointestinal sarcoma located in the stromal cells of the digestive tract, and molecular studies have revealed the pathogenesis of mutations in KIT and PDGFRA genes. Since imatinib opened the era of targeted therapy for GIST, tyrosine kinase inhibitors (TKIs) that can treat GIST have been developed successively. However, the lack of new drugs with satisfactory therapeutic standards has made addressing resistance a significant challenge for TKIs in the face of the resistance to first-line and second-line drugs. Therefore, we need to find as many drugs and new treatments that block mutated genes as possible. METHODS: We conducted a comprehensive collection of literature using databases, integrated and analysed the selected literature based on keywords and the comprehensive nature of the articles, and finally wrote articles based on the content of the studies. RESULTS: In this article, we first briefly explained the relationship between GIST and KIT/ PDGFRα and then introduced the related drug treatment. The research progress of TKIs was analyzed according to the resistance of the drugs. CONCLUSION: This article describes the research progress of some TKIs and provides a brief introduction to the currently approved TKIs and some drugs under investigation that may have better therapeutic effects, hoping to provide clues to the research of new drugs.

16S rRNA and Metagenomics Combined with UPLC-Q/TOF-MS Metabolomics Analysis Reveals the Potential Mechanism of Radix Astragali Against Hyperuricemia in Mice.

Purpose: This study aimed to investigate the underlying treatment mechanism of Radix Astragali (RA) in hyperuricemia from the perspective of microbiota and metabolomics. Methods: We used potassium oxyazinate (PO) to induce hyperuricemia mice, and we determined serum alanine aminotransferase/aspartate aminotransferase (ALT/AST), xanthine oxidase (XOD), creatinine (CRE), uric acid (UA), blood urea nitrogen (BUN) levels, liver XOD levels and assessed the kidney tissue histopathology. The therapeutic mechanism of RA in hyperuricemic mice was studied by 16S rRNA, metagenomic sequencing and metabolomics. Results: Our research showed that RA has therapeutic effect in hyperuricemia mice, such as slow the weight loss, repair kidney damage, and downregulate serum UA, XOD, CRE, ALT/AST, BUN, and liver XOD levels. RA restored the disturbance structure of the microbiota in hyperuricemia mice by increasing the relative abundances of beneficial bacteria (Lactobacillaceae and Lactobacillus murine) but decreasing the relative abundances of pathogenic bacteria (Prevotellaceae, Rikenellaceae and Bacteroidaceae). Meanwhile, we found that RA directly regulated the metabolic pathway (such as linoleic acid metabolism and glycerophospholipid metabolism) and indirectly regulated bile acid metabolism by mediating microbiota to ameliorate metabolic disorders. Subsequently, there was a robust correlation between specific microbiota, metabolites and the disease index. Conclusion: The ability of RA to protect mice against hyperuricemia is strongly linked to the microbiome-metabolite axis, which would provide evidence for RA as a medicine to prevent or treat hyperuricemia.

[Occurrence Characteristics of Microplastics and Metal Elements in the Surface Water of Huangpu River and Their Associations with Metal Resistance Genes].

Urban rivers have been regarded as the "hotspots" for microplastic (MPs) and metal contamination as they play important roles in pollution migration. However, as important sinks and sources of resistance genes, there has been little to no research investigating the associations between MPs, metal contaminations, and metal resistance genes (MRGs). Ten water samples were collected from the Huangpu River in situ; along with metal elements, MPs characteristics analyzed. Metal resistance genes and mobile genetic elements (MGEs) in waters and MPs were detected using metagenomic technology. As a result, the highest metal concentration was that of Sb in surface water (3.16±0.419) µg·L-1. The average abundance of MPs was (1.78±0.84) n·L-1, and the peak levels located in industrial and densely populated areas, which was significantly higher than those in agricultural and low population density areas. Fibrous, small-size (<0.5 mm), and transparent polyethylene terephthalate (PET) were the largest contributors of MPs. Eighteen MRGs were detected in all the samples. The relative abundance of MRGs in water was 1.68±0.21. The most dominant MRGs subtypes were merR and ruvB, which are subtypes resistant to mercury and Multi_metals. Correlation analysis showed that chromium and nickel in waters were significantly positively associated with MRG-Cr, MRG-Ni, and Multi_metals resistance genes. For MPs particles, the relative abundance of MRGs was 1.63±0.53. The most dominant MRGs subtypes were merT-P and copB, which also belong to mercury-resistant and Multi_metals. The Multi_metals resistance gene, ctpC, cueA, czrA, kmtR, etc., had significant positive associations with Ni, Cr, and Sb in waters. Compared with water samples, MPs selectively enriched merT-P, copB, ziaA, sodA, and dmeF. Additionally, the co-occurrence patterns of MRGs and MGEs were explored based on network analysis. In water samples, the transposases (tnpA_1 and tnpA_2), integrase (qacEdelta), and insertion sequence (IS91) were the major contributors of the horizontal gene transfer (HGT) of specific MRGs. Multiple subtypes resistant to copper and Multi_metals resistance genes on MPs were positively associated with IncFIC(FII), Rep7, rep7, and rep13, which were subtypes of plasmids. The presence of MPs exerted a significant impact on HGT of specific MRGs mediated by plasmids.

A Cas12a ortholog with distinct TTNA PAM enables sensitive detection of HPV16/18.

CRISPR-associated (Cas) nucleases are multifunctional tools for gene editing. Cas12a possesses several advantages, including the requirement of a single guide RNA and high fidelity of gene editing. Here, we tested three Cas12a orthologs from human gut samples and identified a LtCas12a that utilizes a TTNA protospacer adjacent motif (PAM) distinct from the canonical TTTV PAM but with equivalent cleavage ability and specificity. These features significantly broadened the targeting scope of Cas12a family. Furthermore, we developed a sensitive, accurate, and rapid human papillomavirus (HPV) 16/18 gene detection platform based on LtCas12a DNA endonuclease-targeted CRISPR trans reporter (DETECTR) and lateral flow assay (LFA). LtCas12a showed comparable sensitivity to quantitative polymerase chain reaction (qPCR) and no cross-reaction with 13 other high-risk HPV genotypes in detecting the HPV16/18 L1 gene. Taken together, LtCas12a can broaden the applications of the CRISPR-Cas12a family and serve as a promising next-generation tool for therapeutic application and molecular diagnosis.

Infusion of GMSCs relieves autoimmune arthritis by suppressing the externalization of neutrophil extracellular traps via PGE2-PKA-ERK axis.

INTRODUCTION: Rheumatoid arthritis (RA) is a systemic autoimmune disease with limited treatment success, characterized by chronic inflammation and progressive cartilage and bone destruction. Accumulating evidence has shown that neutrophil extracellular traps (NETs) released by activated neutrophils are important for initiating and perpetuating synovial inflammation and thereby could be a promising therapeutic target for RA. K/B×N serum transfer-induced arthritis (STIA) is a rapidly developed joint inflammatory model that somehow mimics the inflammatory response in patients with RA. Human gingival-derived mesenchymal stem cells (GMSCs) have been previously shown to possess immunosuppressive effects in arthritis and humanized animal models. However, it is unknown whether GMSCs can manage neutrophils in autoimmune arthritis. OBJECTIVES: To evaluate whether infusion of GMSCs can alleviate RA by regulating neutrophils and NETs formation. If this is so, we will explore the underlying mechanism(s) in an animal model of inflammatory arthritis . METHODS: The effects of GMSCs on RA were assessed by comparing the symptoms of the K/B×N serum transfer-induced arthritis (STIA) model administered either with GMSCs or with control cells. Phenotypes examined included clinical scores, rear ankle thickness, paw swelling, inflammation, synovial cell proliferation, and immune cell frequency. The regulation of GMSCs on NETs was examined through immunofluorescence and immunoblotting in GMSCs-infused STIA mice and in an in vitro co-culture system of neutrophils with GMSCs. The molecular mechanism(s) by which GMSCs regulate NETs was explored both in vitro and in vivo by silencing experiments. RESULTS: We found in this study that adoptive transfer of GMSCs into STIA mice significantly ameliorated experimental arthritis and reduced neutrophil infiltration and NET formation. In vitro studies also showed that GMSCs inhibited the generation of NETs in neutrophils. Subsequent investigations revealed that GMSCs secreted prostaglandin E2 (PGE2) to activate protein kinase A (PKA), which ultimately inhibited the downstream extracellular signal-regulated kinase (ERK) pathway that is essential for NET formation. CONCLUSION: Our results demonstrate that infusion of GMSCs can ameliorate inflammatory arthritis mainly by suppressing NET formation via the PGE2-PKA-ERK signaling pathway. These findings further support the notion that the manipulation of GMSCs is a promising stem cell-based therapy for patients with RA and other autoimmune and inflammatory diseases.

The LINC00501-HSP90B1-STAT3 positive feedback loop promotes malignant behavior in gastric cancer cells.

Long non-coding RNAs (lncRNAs) have been implicated in gastric cancer (GC) carcinogenesis and progression. However, the role of LINC00501 in GC growth and metastasis remains unclear. In this study, we found that LINC00501 was frequently upregulated in GC cells and tissues and was closely related to adverse GC clinicopathological features. Aberrant overexpression of LINC00501 promoted GC cell proliferation, invasion, and metastasis both in vitro and in vivo. Mechanistically, LINC00501 stabilized client protein STAT3 from deubiquitylation by directly interacting with cancer chaperone protein HSP90B1. Furthermore, the LINC00501-STAT3 axis modulated GC cell proliferation and metastasis. In turn, STAT3 bound directly to the LINC00501 promoter and positively activated LINC00501 expression, thus forming a positive feedback loop, thereby accelerating tumor growth, invasiveness, and metastasis. In addition, LINC00501 expression was positively correlated with STAT3 and p-STAT3 protein expression levels in gastric clinical samples. Our results reveal that LINC00501 acts as an oncogenic lncRNA and that the LINC00501-HSP90B1-STAT3 positive feedback loop contributes to GC development and progression, suggesting that LINC00501 may be a novel potential biomarker and treatment target for GC.

Diffuse gastric polyposis in a young patient with a giant retroperitoneal mass: A case report.

Familial adenomatous polyposis (FAP) is characterized by hundreds of colonic adenomatous polyps and extraintestinal manifestations beginning in adolescence and early adulthood. It is also one of the most common hereditary colorectal cancer syndromes. In this case study, a rare phenotype of FAP associated with diffuse gastric polyposis, colon oligo-polyposis, and a massive retroperitoneal mass is described. The results expand on the current body of knowledge of FAP and may represent a new phenotypic expression of FAP. Accurate evidence-based surveillance and management recommendations for this disease require further research and evaluation.

Prostate-specific antigen reduction after capecitabine plus oxaliplatin chemotherapy: A case report.

BACKGROUND: Prostate cancer (PC) is currently the most common malignant tumor of the genitourinary system in men. Radical prostatectomy (RP) is recommended for the treatment of patients with localized PC. Adjuvant hormonal therapy (AHT) can be administered postoperatively in patients with high-risk or locally advanced PC. Chemotherapy is a vital remedy for castration-resistant prostate cancer (CRPC), and may also benefit patients with PC who have not progressed to CRPC. CASE SUMMARY: A 68-year-old male was admitted to our hospital because of urinary irritation and dysuria with increased prostate-specific antigen (PSA) levels. After detailed examination, he was diagnosed with PC and treated with laparoscopic RP on August 3, 2020. AHT using androgen deprivation therapy (ADT) was performed postoperatively because of the positive surgical margin, extracapsular extension, and neural invasion but lasted only 6 mo. Unfortunately, he was diagnosed with rectal cancer about half a year after self-cessation of AHT, and was then treated with laparoscopic radical rectal resection and adjuvant chemotherapy using the capecitabine plus oxaliplatin (CapeOx) regimen. During the entire treatment process, the patient's PSA level first declined significantly after treatment of PC with laparoscopic RP and ADT, then rebounded because of self-cessation of ADT, and finally decreased again after CapeOx chemotherapy. CONCLUSION: CapeOx chemotherapy can reduce PSA levels in patients with high-risk locally advanced PC, indicating that CapeOx may be an alternative chemotherapy regimen for PC.

A strand displacement signal amplification-assisted fluorescence assay for sensitive detection of microRNA.

MicroRNA is a vital biomarker because of its abnormal expression in the emergence and development of diseases, especially in cancers. Herein, a label-free fluorescent sensing platform is proposed for detecting microRNA-21, coupled with the cascade toehold-mediated strand displacement reaction and magnetic beads. Target microRNA-21 acts as an initiator to trigger the cascade toehold-mediated strand displacement reaction and it outputs double-stranded DNA. After magnetic separation, the double-stranded DNA is intercalated by SYBR Green I, resulting in an amplified fluorescent signal. Under the optimal conditions, a wide linear range (0.5-60 nmol/L) and low limits of detection (0.19 nmol/L) are exhibited. What's more, the biosensor shows great specificity and reliability between microRNA-21 and other microRNAs involved in cancer (microRNA-34a, microRNA-155, microRNA-10b, and let-7a). Owing to the properties of fabulous sensitivity, high selectivity, and simplicity of operator, the proposed method paves a promising way for microRNA-21 detection in cancer diagnosis and biological research.

The HOXD9-mediated PAXIP1-AS1 regulates gastric cancer progression through PABPC1/PAK1 modulation.

Long non-coding RNAs (lncRNAs) have been functionally characterised in various diseases. LncRNA PAX-interacting protein 1-antisense RNA 1 (PAXIP1-AS1) has reportedly been associated with cancer development. However, its role in gastric cancer (GC) remains poorly understood. Here, we showed that PAXIP1-AS1 was transcriptionally repressed by homeobox D9 (HOXD9) and was significantly downregulated in GC tissues and cells. Decreased expression of PAXIP1-AS1 was positively correlated with tumour progression, while PAXIP1-AS1 overexpression inhibited cell growth and metastasis both in vitro and in vivo. PAXIP1-AS1 overexpression significantly attenuated HOXD9-enhanced epithelial-to-mesenchymal transition (EMT), invasion and metastasis in GC cells. Poly(A)-binding protein cytoplasmic 1 (PABPC1), an RNA-binding protein, was found to enhance the stability of PAK1 mRNA, leading to EMT progress and GC metastasis. PAXIP1-AS1 was found to directly bind to and destabilise PABPC1, thereby regulating EMT and metastasis of GC cells. In summary, PAXIP1-AS1 suppressed metastasis, and the HOXD9/PAXIP1-AS1/PABPC1/PAK1 signalling axis may be involved in the progression of GC.

The Role of LincRNA-EPS/Sirt1/Autophagy Pathway in the Neuroprotection Process by Hydrogen against OGD/R-Induced Hippocampal HT22 Cells Injury.

Cerebral ischemia/reperfusion (CI/R) injury causes high disability and mortality. Hydrogen (H2) enhances tolerance to an announced ischemic event; however, the therapeutic targets for the effective treatment of CI/R injury remain uncertain. Long non-coding RNA lincRNA-erythroid prosurvival (EPS) (lincRNA-EPS) regulate various biological processes, but their involvement in the effects of H2 and their associated underlying mechanisms still needs clarification. Herein, we examine the function of the lincRNA-EPS/Sirt1/autophagy pathway in the neuroprotection of H2 against CI/R injury. HT22 cells and an oxygen-glucose deprivation/reoxygenation (OGD/R) model were used to mimic CI/R injury in vitro. H2, 3-MA (an autophagy inhibitor), and RAPA (an autophagy agonist) were then administered, respectively. Autophagy, neuro-proinflammation, and apoptosis were evaluated by Western blot, enzyme-linked immunosorbent assay, immunofluorescence staining, real-time PCR, and flow cytometry. The results demonstrated that H2 attenuated HT22 cell injury, which would be confirmed by the improved cell survival rate and decreased levels of lactate dehydrogenase. Furthermore, H2 remarkably improved cell injury after OGD/R insult via decreasing pro-inflammatory factors, as well as suppressing apoptosis. Intriguingly, the protection of H2 against neuronal OGD/R injury was abolished by rapamycin. Importantly, the ability of H2 to promote lincRNA-EPS and Sirt1 expression and inhibit autophagy were abrogated by the siRNA-lincRNA-EPS. Taken together, the findings proved that neuronal cell injury caused by OGD/R is efficiently prevented by H2 via modulating lincRNA-EPS/Sirt1/autophagy-dependent pathway. It was hinted that lincRNA-EPS might be a potential target for the H2 treatment of CI/R injury.

The association between childbirth-related fear, childbirth readiness, and fertility intentions, and childbirth readiness as the mediator.

BACKGROUND: Fertility intentions have been proved to be a reliable predictor of actual fertility behaviour. Also, childbirth-related fear (CBRF) has been proven to be negatively associated with childbirth readiness and fertility intentions among women, while childbirth readiness was positively related to fertility intentions. However, the associations and potential mechanisms between CBRF, childbirth readiness, and fertility intentions remain unknown. This study aimed to investigate the unique association between CBRF, childbirth readiness, and fertility intentions and whether childbirth readiness would mediate the relationship between CBRF and fertility intentions. METHOD: A cross-sectional study of women (N = 1119, aged 16-53 years) who gave birth within 72 h was conducted. Using a convenience sampling, women were recruited from obstetric wards-10 comprehensive hospitals and 3 specialized hospitals in 7 provinces in mainland China. Pearson correlation was used to examine the relationship between CBRF, childbirth readiness, fertility intentions, and social support. Multivariate linear regression was further used to analyze the association between demographic and personal characteristics, CBRF, childbirth readiness, and fertility intentions. Mediation analysis was used to examine whether childbirth readiness mediates the relationship between CBRF and fertility intentions. RESULTS: Women with high childbirth readiness (ß = 0.09, P = 0.002) had higher fertility intentions. However, women with high CBRF (ß = - 0.17, P < 0.001) were more likely to have lower fertility intentions. CBRF had both direct and indirect effects on the level of fertility intentions. As predicted, childbirth readiness mediated the relationship between CBRF and the level of fertility intentions (estimate = - 0.012, 95% bootstrap CI: - 0.021 to - 0.005). Higher CBRF was associated with lower scores of childbirth readiness, which was associated with lower levels of fertility intentions. CONCLUSIONS: This study established the evidence that CBRF had both direct and indirect effects on the level of fertility intentions and childbirth readiness mediated the relationship between CBRF and the level of fertility intentions. Specifically, higher CBRF was associated with lower scores of childbirth readiness, which was associated with lower levels of fertility intentions. This finding suggested that it is important for health policymakers and health providers to pay more attention to improving women's childbirth readiness, which might reduce the negative influence of CBRF on fertility intentions, thus strengthening their fertility intentions.

Over the past two decades, fertility rates have been dropping steadily in most countries. Fertility intentions have been proven to be a reliable predictor of actual fertility behaviour. The worldwide sluggish fertility trend has brought about a series of issues, such as accelerated population ageing, shrinking workforce, and economic decline. China has the largest national population in the world, accounting for nearly one-fifth of the world's population, thus having a huge impact on global population trends. Therefore, in the context of significant fertility decline and population policy changes, timely research on fertility intention is of great significance for China and other low-fertility countries. CBRF has been proven to be negatively associated with childbirth readiness and fertility intentions among women, while childbirth readiness was positively related to fertility intentions. This study aimed to investigate the unique association between fertility intentions, CBRF, and childbirth readiness, and whether childbirth readiness would mediate the relationship between CBRF and fertility intentions. In this cross-sectional study, we found that women with high childbirth readiness had higher fertility intentions. However, women with high CBRF were more likely to have lower fertility intentions. Furthermore, CBRF had both direct and indirect effects on the level of fertility intentions. Childbirth readiness mediated the relationship between CBRF and the level of fertility intentions. Higher CBRF was associated with lower scores of childbirth readiness, which was associated with lower levels of fertility intentions. This finding suggested that it is important for health policymakers and health providers to pay more attention to improving women's childbirth readiness, which might reduce the negative influence of CBRF on fertility intentions, thus strengthening their fertility intentions.