OBJECTIVE:This study aimed to examine the associations between trimester-specific bisphenol exposure and preterm birth (PTB) and explore potential underlying mechanisms. METHODS:Within the Tongji Precision Birth Cohort (TPBC), concentrations of ten bisphenols were quantified using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Multivariable logistic regression models were employed to examine associations between trimester-specific urinary bisphenol exposure and spontaneous PTB (sPTB). Placental expressions of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were evaluated by immunohistochemistry. Median urinary concentrations of Bisphenol A (BPA) and BPF were used to guide in vitro assays. HTR8 and BeWo trophoblast cell lines were exposed to gradient BPA and BPF. RT-qPCR was used to measure mRNA levels of NF-κB pathway-related genes. RESULTS:Among the bisphenols analyzed, BPF emerged as the most common alternative to BPA. Placental BPA and urinary BPF showed associations with sPTB risk. Each standard deviation increase in placental BPA concentration was associated with a 38.1% increased risk of spontaneous preterm birth (95% CI: 1.023-1.866, p = 0.035). Placental expression of IL-6 and TNF-α was increased in sPTB. In trophoblast cells, low to middle concentrations of BPA and BPF might upregulate NF-κB pathway-related genes and selected inflammatory markers. CONCLUSIONS:Bisphenol exposure during pregnancy, particular BPA and BPF, may be associated with increased risk of sPTB. The findings further suggest the involvement of NF-κB pathway-related placental inflammatory signaling.

Accurate identification of disease vectors is crucial for public health, yet distinguishing morphologically similar species demands significant taxonomic expertise and data resources. This study proposes MVP-Net, an AI-driven framework designed to extract a minimal sufficient set of diagnostic anatomical views from multi-view imagery for efficient identification. The framework was evaluated on regionally collected datasets of Calyptratae (8 views) and Culicidae (11 views) from routine surveillance in Shanghai. Under all-view fusion, MVP-Net achieved Top-1 accuracies of 87.04% for Calyptratae and 100% for Culicidae. After Pareto-based view optimization, the required input was reduced to 5 views for Calyptratae and 2 views for Culicidae, lowering computational cost by 37.49% and 81.82%, respectively, while retaining comparable classification performance (86.11% for the recommended Calyptratae configuration and 100% for the recommended Culicidae configuration). These results show that MVP-Net can reduce view redundancy while preserving comparable identification performance within the current Shanghai surveillance setting, providing a practical approach for optimizing regional multi-view auxiliary identification workflows.

Left–right (LR) asymmetry disorders present a complex etiology, with genetic factors emerging as a primary contributor. This study aims to explore the genetic underpinnings of chromosomal variants and individual genes in fetuses afflicted with prenatal LR asymmetry disorder. Through a retrospective analysis conducted between 2020 and 2023 at Tongji Hospital, Huazhong University of Science and Technology, genetic outcomes of LR asymmetric disorder were scrutinized utilizing copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) methodologies. With a combination of CNV-seq and WES, 5 fetuses in 17 patients with LR asymmetry had chromosomal or genetic variants. CNV-seq revealed a 16p11.2 microdeletion syndrome in a situs inversus fetus presenting pathogenic and a 2q36.3 microduplication syndrome in a fetus with Heterotaxy presenting a variant of uncertain significance (VUS). WES identified NM_198075.4:c.755del in the LRRC56 gene and NM_001454.4:c.865_868dup in the FOXJ1 gene in two situs inversus cases, along with two variants in DNAH5 in two other fetuses. Further bioinformatics scrutiny was conducted to assess the protein structure and function prediction of these variants, ultimately indicating their potential pathogenicity. The study highlights that fetuses with LR asymmetric disorders may have copy number variants, underscoring the significance of mutations in LRRC56 and FOXJ1 in the development of LR asymmetry disorders.

Sensory impairments (SI), including vision (VI), hearing (HI), and dual sensory impairments (DSI), are prevalent with aging, but their impact on disease risk remains unclear. This study investigates the epidemiological and genetic associations between SIs and 10 chronic disease categories and multimorbidity. Using the CHARLS study, participants were classified by their self-reported VI/HI/DSI status in 2011 and 2013 into groups: “new onset, remission, persistent, and no SI.” Their chronic disease incidence was tracked until 2018 in sub-cohorts respectively. Mendelian randomization (MR) analyses used genetic instruments from UK Biobank GWAS data on 88,250/504,307 individuals for vision/hearing loss, with outcome datasets from consortia including FinnGen, DIAMANTE, CKDGen, PGC, GWAS Catalog, and International Parkinson’s Disease Genomics Consortium. The cohort study revealed that persistent HI significantly increased the risk of heart disease (P < 0.001, HR 1.63, 95

Bacterial detection is pivotal for the timely diagnosis and effective treatment of infectious diseases. Microfluidic platforms offer advantages over traditional methods, including heightened sensitivity, rapid analysis, and minimal sample volume requirements. Traditional clinical methods for bacterial identification often involve extended processing times and necessitate high pathogen concentrations, resulting in delayed diagnoses and missed treatment opportunities. Microfluidic technology overcomes these limitations by facilitating rapid bacterial identification at lower biomass levels, thus ensuring prompt and precise treatment interventions. Additionally, bacteria-driven inflammation has been associated with the development and progression of various diseases, including cancer. Elucidating the complex interplay between bacteria, inflammation, and disease is essential for devising effective disease models and therapeutic strategies. Microfluidic platforms have been used to construct in vitro disease models that accurately replicate the intricate microenvironment that bacteria-driven inflammation affects. These models offer valuable insights into bacteria-driven inflammation and its impact on disease progression, such as cancer metastasis and therapeutic responses. This review examines recent advancements in bacterial detection using microfluidics and assesses the potential of this technology as a robust tool for exploring bacteria-driven inflammation in the context of cancer.

OBJECTIVE:Great obstetrical syndrome (GOS) represents a group of pregnancy-related diseases that result in inadequate placentation. Most GOS cases end in preterm, either spontaneously or indicatively, and the use of antenatal corticosteroids (ACS) is inevitably discussed. The placenta is an important, transient fetal-derived organ and is the embodiment of maternal or fetal well-being. However, few studies provide histological evidence of the placenta in GOS. This study aims to address these issues. METHODS:A total of 831 pregnant women were prospectively recruited. Placenta tissue was collected immediately and fixed with 4% paraformaldehyde solution for future H&E analysis. A novel checklist was devised to evaluate maternal vascular malperfusion sections on the basis of the commonly accepted Amsterdam placental workshop group consensus statement. RESULTS:A total of 131 patients were classified as having GOS. Comparisons between those with and without GOS revealed significant differences, including higher levels of distal villous hypoplasia, increased syncytial knots, accelerated villous maturation, and higher total scores in GOS. We found significant negative associations between GOS and neonatal weight, neonatal height, head circumference, placental surface area, placental volume, and placenta gross examination score. GOS neonates were 1.25 times more likely to have hyperbilirubinemia. Regarding the effect of ACS, a significant reduction in birthweight, height, and head circumference was observed, along with an increased risk of hyperbilirubinemia. CONCLUSION:This study provides histological evidence of the GOS that supports the defective deep placentation hypothesis. Our research also contributes to benefit-risk consultation in the GOS, such as in cases of PE and FGR, where a balance between fetal lung maturation and short-term neonatal outcomes is crucial.

The multidrug-resistant Acinetobacter baumannii clonal complex 92 is spreading worldwide due to its high-frequency gene mutation and recombination, posing a significant threat to global medical and health safety. Between November 2021 and April 2022, a total of 132 clinical A. baumannii isolates were collected from a tertiary hospital in China. Their growth ability and virulence of these isolates were assessed using growth curve analyses and the Galleria mellonella infection model. The genetic characteristics of the isolates were further examined through whole-genome sequencing. ST1791O/ST2P isolates represented the largest proportion of isolates in our collection and exhibited the highest growth rate and strongest virulence among all sequence types (STs) analyzed. Whole-genome sequences from 14,159 clinical isolates were collected from the National Center for Biotechnology Information database, and only nine ST1791O/ST2P isolates were detected. Comparative genomic analysis revealed that ST1791O/ST2P carried 11 unique genes, 5 of which were located within the capsular polysaccharide synthesis (cps) gene cluster. Single nucleotide polymorphisms (SNPs) between ST1791O/ST2P and other isolates were primarily found in the cps gene cluster. Among the other isolates, ST195O/ST2P and ST208O/ST2P exhibited the smallest SNP differences from ST1791O/ST2P, while ST195O/ST2P and ST1486O/ST2P had high homology. The ST1791O/ST2P strain in Anhui, China, displayed significant homology with ST195O/ST2P, ST208O/ST2P, and ST1486O/ST2P isolates. Compared to other isolates in this study, ST1791O/ST2P exhibited strong growth ability and virulence. Therefore, preventing the further spread of ST1791O/ST2P should be a top public health priority.

Some observational studies found that there is an epidemiological association between type 2 diabetes (T2D) and sleep apnea (SA) and glucose-lowering drugs may lower SA risk. However, the causative relationship among them remains unclear. Linkage Disequilibrium Score Regression (LDSC) was utilized to assess the genetic correlation between T2D and SA. Mendelian Randomization (MR) was applied, primarily using the inverse variance weighted (IVW) method, to evaluate the causal relationship between T2D and SA. Additionally, we performed Drug-target MR analysis to evaluate the impact of Glucagon-like Peptide-1 Receptor Agonists (GLP-1RAs) on SA. We used two kinds of genetic instruments to proxy the exposure of GLP-1RAs, including expression quantitative trait loci of drugs target genes, and genetic variants within drugs target genes associated with glycated hemoglobin A1c(HbA1c) from genome wide association study. Summary-data-based MR (SMR) and IVW were used to calculate the effect estimates. A two-step MR analysis was further employed to explore potential mediating factors in the T2D-SA relationship. A genetic correlation and bidirectional causal association were found between T2D and SA. GLP-1RAs-mediated reductions in HbA1c levels showed associations with decreased SA risk in two independent datasets: (odds ratio (OR)1 = 0.48 [95

The primary objective of this study was to examine whether ARID1A mutations confer a fitness advantage to gastric cancer from an immunological perspective, along with elucidating the underlying mechanism. Additionally, we aimed to identify the clinical potential of combining epigenetic inhibitors with immune checkpoint inhibitors to improve the efficacy of immunotherapy for gastric cancer. The correlation between ARID1A gene expression and gastric cancer patient survival was analyzed using the GEO dataset GSE62254. The association between chemokines (CXCL9, CXCL10) and ARID1A was conducted using GSE15460 dataset. Real-time PCR was employed for gene expression analysis, while chromatin immunoprecipitation was used to identify transcriptional regulation on target genes. Protein expression and regulation were assessed through various techniques, including Western blot, ELISA, immunohistochemistry, and immunofluorescence. Chromatin DNA accessibility was determined through MNase digestions, transmission electron microscopy, and ChIP-seq. The impact of ARID1A expression and epigenetic inhibitors on tumor immunity in mice was assessed using flow cytometry. ARID1A expression demonstrated a positive correlation with CD8+ T cell infiltration and clinical prognosis. The loss of ARID1A expression led to impaired Th1-type chemokines. Additionally, ARID1A depletion was associated with enhanced tumor growth and the absence of CD8+ T cells within the tumor microenvironment. The study revealed that ARID1A played a role in promoting histone acetylation and facilitating chromatin accessibility. Notably, the application of deacetylase inhibitors effectively reversed the effects of ARID1A depletion on tumor progression and significantly enhanced the efficacy of immunotherapy. Gastric cancer with ARID1A mutations modulates immune cell chemotaxis within the tumor microenvironment by influencing histone acetylation. Deacetylase inhibitors have the potential to alter the secretion of chemokines for tumor immune cells, consequently enhancing the effectiveness of immune checkpoint inhibitor therapy in ARID1A-mutated gastric cancer.

The Glucagon-like peptide-1 receptor (GLP-1R) and the glucose-dependent insulinotropic polypeptide receptor (GIPR) are well-established drug targets for the treatment of diabetes and obesity. Studies have linked GLP-1R agonist to cardiometabolic diseases (CMDs), while the therapeutic potential of the GIPR agonist remains a topic of debate. Using genetic variants as instrumental variables, we performed a two-sample Mendelian randomization (MR) analysis to investigate causal relationships between genetically proxied GIPR agonist and 23 CMD outcomes, and a two-step mediation analysis to identify mediating inflammatory biomarkers. The inverse variance weighted (IVW) method served as the primary analytical approach, supplemented by sensitivity analyses to validate robustness. The genetic mimicry of GIPR enhancement showed significant protective associations with 14 CMDs. Mediation analysis revealed that Fms-related tyrosine kinase 3 ligand (Flt3L) partially mediated the effects of GIPR agonist on angina (OR 0.997 [0.995–0.999], P = 0.0048) and myocardial infarction(MI) (OR 0.998 [0.996–0.999], P = 0.0077), accounting for 15.49

OBJECTIVE:Sleep is fundamental to the physical and mental health of both the general population and pregnant women. Most studies have focused on the impact of certain trimester sleep behaviors on gestational complications and birth outcomes. This study aimed to explore the association between maternal sleep duration and fetal growth development from as early as 23 gestational weeks to birth. METHODS:A total of 803 pregnant women were prospectively enrolled. The self-reported maternal nocturnal sleep duration during all 3 trimesters was recorded. The outcome measures were reference-population-based Z-scores of fetal biometric measurements obtained through routine ultrasonographic examination. RESULTS:Using multiple linear regression, a marginally significant negative association was observed between second-trimester sleep duration and second-trimester fetal head circumference (HC) and third-trimester fetal biparietal diameter (BPD). Then the associations of long sleep duration in each trimester with fetal biometry extreme values were evaluated. A significant impact of second-trimester long sleep duration on the second-trimester BPD below the 10th percentile of the reference population was observed. Longitudinal analysis reported similar results for BPD and HC. CONCLUSIONS:Overall, a negative association between sleep duration and fetal biometric measurements was observed. Long sleep durations in the second trimester might negatively impact fetal growth, particularly brain parameters, including BPD and HC.

The cell membrane, as the boundary of the cellular system, plays an extremely important role in the regulation of cellular metabolism, substance transport, information exchange and cellular immunity. Complement component 1q subcomponent binding protein (C1QBP) is a ubiquitously expressed cellular protein, and although multiple studies have suggested that C1QBP may play an important role in cancer, the functions and mechanisms of C1QBP in the progression of many tumors remain unknown. We performed bioinformatics analysis and found that C1QBP was significantly overexpressed in a variety of tumor tissues and that high C1QBP expression correlates strongly with poor prognosis in tumor patients. Further validation in cholangiocarcinoma(CCA) revealed that C1QBP is the most upregulated membrane protein in CCA, where it is involved in energy metabolism, DNA repair, and tolerance to platinum-based chemotherapeutic agents. It also correlates strongly with CCA proliferation and poor prognosis, while silencing of C1QBP significantly inhibits CCA growth in mice. Mechanistic studies further demonstrated that c-MYC can upregulate C1QBP expression at the transcriptional level, subsequently influencing PAICS/FAK expression and promoting CCA growth. Interestingly, C1QBP also regulates c-MYC expression by increasing FAK phosphorylation, establishing a positive feedback loop that drives tumor progression. Additionally, we developed a novel siRNA delivery system, HA gel-siC1QBP, by encapsulating siC1QBP within hyaluronic acid-dopamine hydrogel-coated liposomes. In vivo experiments confirmed its ability to provide prolonged and stable C1QBP inhibition along with enhanced antitumor efficacy. In conclusion, our study suggests that C1QBP may serve as a valuable biomarker for tumour prognosis and that silencing C1QBP using HA gel-siC1QBP —either alone or combined with targeted/ immunotherapies —represents a promising therapeutic strategy against tumors.

The balance between lipid synthesis and lipid catabolism is critical to maintain energy homeostasis. Lipophagy and lipolysis are two important pathways for lipid selective catabolism. Defects in lipophagy and lipolysis are linked to lipid metabolic diseases. Transcription factor EB (TFEB) is a master regulator of autophagy and lysosome biogenesis, as well as lipid metabolism by promoting expression of genes encoding fat catabolic lipases. Therefore, targeting TFEB provides a novel potential strategy for the treatment of lipid metabolic diseases. In this study, we showed that the TFEB activator clomiphene citrate (CC) activated the autophagy-lysosome and lipolysis pathways, and promoted degradation of lipid droplets induced by the free fatty acids oleate and palmitate in HepG2 cells. Moreover, CC treatment promoted lipid catabolism and attenuated obesity, restored lipid levels, blood glucose levels and insulin resistance, hepatocellular injury and hepatic steatosis, as well as liver inflammation in the HFD fed mice. In addition, we found that En-CC, a trans-isomer of CC, displayed less toxicity and more efficient activation of TFEB. Consistent with CC, En-CC treatment improved lipid metabolic syndrome pathology. These findings demonstrate that CC promotes clearance of lipids and ameliorates HFD-induced lipid metabolic syndrome pathology through activating TFEB-mediated lipophagy and lipolysis, indicating that CC has the potential to be used to treat lipid metabolic diseases.

The study examines the management of national government-appointed expert and advisory committees (EACs) in China, focusing on their role in generating alternative policy advice and influencing policy processes under the lens of the policy advisory system (PAS). Based on content analysis and case studies, it finds that rules are, in general, designed to facilitate national EACs to produce and incorporate alternative policy advice. However, on many occasions, the management of national EACs has not maintained a balance between relevance to policymakers and their institutional autonomy, as well as between collective problem-solving and representative capacity in providing alternative policy advice. The management of these EACs' membership and advisory activities by the appointing authority could constrain their capacity to integrate grassroots perspectives into policy advice. The cases of family planning policy changes and dynamic-zero-COVID-19 policy changes demonstrate that when the policies are implemented from the Party center through strict political accountability measures, top political leaders can open up other venues within the PAS, beyond the ministerial EAC, to solicit and utilize alternative policy advice. In such cases, timely decision-making through political learning by political authorities is needed to address uncertainties and conflicts within the PAS.

PURPOSE:Cardiac hypertrophy is a critical contributor to heart failure. Therapies that effectively manage cardiac hypertrophy are still inadequate. Crocin is a natural component of saffron, and its beneficial properties have been previously documented. This study aimed to investigate the role of crocin in cardiac hypertrophy and apoptosis and its related mechanisms. METHODS:Sprague-Dawley rats were infused with angiotensin II (Ang II; 520 ng/kg/min) or normal saline and then intraperitoneally injected with crocin (40 mg/kg) or dimethyl sulfoxide for 4 weeks. Systolic and diastolic blood pressure were recorded. Cardiac hypertrophy was evaluated by echocardiography, heart weight, hematoxylin-eosin staining, TUNEL assay, and gene expression. For in vitro studies, H9C2 cells were treated with Ang II (1 μM) for 48 hours to induce cardiac hypertrophy-like conditions. An immunofluorescence assay was used for [Formula: see text]-actinin staining. reverse transcription quantitative real-time polymerase chain reaction was performed to measure the expression of hypertrophic markers, and western blotting was used to detect apoptosis and underlying mechanisms. RESULTS:Our findings revealed that crocin attenuated diastolic dysfunction, cardiac hypertrophy, and apoptosis caused by Ang II in vivo. Additionally, crocin prevented Ang II-stimulated cardiomyocyte enlargement and apoptosis in vitro. Mechanistically, crocin induced AMP-activated protein kinase (AMPK)[Formula: see text] activation and mTOR/p70S6K inhibition in cellular and animal models of cardiac hypertrophy. Moreover, AMPK inhibition abolished the anti-hypertrophic effect of crocin in vitro, while mTOR inhibition enhanced the protective effect of crocin against Ang II-induced cardiomyocyte hypertrophy. CONCLUSION:This study demonstrates that crocin can ameliorate Ang II-stimulated cardiac hypertrophy in vivo and in vitro by regulating AMPK[Formula: see text]/mTOR/ p70S6K signalling.

Background and aims Neointimal hyperplasia is a key pathology in Type 2 Diabetes Mellitus (T2DM) vascular complications. It involves phenotypic switching of vascular smooth muscle cells (VSMCs) triggered by hyperglycemia, though the exact mechanisms remain unclear. Methods We employed Twist1 vascular smooth muscle-specific knockout mice with carotid artery ligation in a T2DM model to study Twist1's role in diabetic neointimal hyperplasia. In vitro, we examined how hyperglycemia via Pkcβ/Ikkβ/Nf-κb pathway affects Twist1's regulation of contractile proteins, matrix molecules, cell morphology, migration, and proliferation in rat VSMCs using Western blotting, immunofluorescence, wound healing assays, and EdU incorporation. Co-immunoprecipitation and colocalization assessed how Twist1-p300 interaction under high glucose affects Myocardin-Srf binding. Results Twist1 was significantly upregulated in VSMCs of T2DM mice. Vascular smooth muscle-specific Twist1 knockout reduced neointimal formation after vascular injury in T2DM. High glucose activated Pkcβ/Ikkβ/Nf-κb pathway, promoting Twist1 upregulation and nuclear translocation, decreasing contractile protein expression while increasing matrix molecules and VSMC proliferation/migration. Mechanistically, upregulated Twist1 increased p300 binding, blocking p300's transcriptional co-activation of Myocardin/Srf and inhibiting contractile gene transcription in VSMCs. Conclusions Hyperglycemia activates the PKCβ/IKKβ/NF-κB pathway, upregulating Twist1 and promoting its nuclear translocation. Twist1 binding to p300 inhibits Myocardin/SRF-mediated contractile gene transcription, leading to VSMC phenotypic switching and neointimal hyperplasia. These findings highlight Twist1 as a potential therapeutic target for diabetic vascular complications.

Multidrug-resistant Enterobacteriaceae, a prominent family of gram-negative pathogenic bacteria, causes a wide range of severe diseases. Strains carrying the mobile colistin resistance (mcr-1) gene show resistance to polymyxin, the last line of defense against multidrug-resistant gram-negative bacteria. However, the transmission of mcr-1 is not well understood. In this study, genomes of mcr-1-positive strains were obtained from the NCBI database, revealing their widespread distribution in China. We also showed that ISApl1, a crucial factor in mcr-1 transmission, is capable of self-transposition. Moreover, the self-cyclization of ISApl1 is mediated by its own encoded transposase. The electrophoretic mobility shift assay experiment validated that the transposase can bind to the inverted repeats (IRs) on both ends, facilitating the cyclization of ISApl1. Through knockout or shortening of IRs at both ends of ISApl1, we demonstrated that the cyclization of ISApl1 is dependent on the sequences of the IRs at both ends. Simultaneously, altering the ATCG content of the bases at both ends of ISApl1 can impact the excision rate by modifying the binding ability between IRs and ISAPL1. Finally, we showed that heat-unstable nucleoid protein (HU) can inhibit ISApl1 transposition by binding to the IRs and preventing ISAPL1 binding and expression. In conclusion, the regulation of ISApl1-self-circling is predominantly controlled by the inverted repeat (IR) sequence and the HU protein. This molecular mechanism deepens our comprehension of mcr-1 dissemination.

RATIONALE:The geographic spread of Japanese spotted fever (JSF) in China is gradually expanding, particularly in regions where severe fever with thrombocytopenia syndrome (SFTS) is highly prevalent, with both diseases sharing similarities in epidemiology and clinical presentation. The microbiological diagnosis of JSF is challenging, compounded by low awareness among healthcare professionals in newly affected areas. Moreover, primary healthcare facilities without polymerase chain reaction (PCR) testing capabilities for SFTS often misdiagnose JSF as SFTS. PATIENT CONCERNS:All 3 patients had a history of working in the fields, with cold like symptoms in the early fever stages, but the fever did not improve after a few days. The accompanying symptoms were also very different. Physical examination revealed enlarged lymph nodes, different forms of rash, with or without eschar. Laboratory tests showed thrombocytopenia, eosinophilia, elevated lactate dehydrogenase, and transaminase, with 1 patient experiencing renal damage. It is worth noting that these 3 patients reside in an area where SFTS is endemic, and there have been no prior reports of JSF. They exhibited clinical symptoms and laboratory test results closely resembling those of SFTS. Therefore, they were initially misdiagnosed with SFTS in their local hospitals. DIAGNOSES:The 3 patients who arrived at our hospital 7 days after symptom onset and were subsequently diagnosed with JSF by metagenomic next-generation sequencing (mNGS). INTERVENTIONS:Doxycycline treatment for 1 week. OUTCOMES:The patients' symptoms quickly improved with no side effects, and the results of laboratory tests went back to normal. LESSONS:By comparing the clinical characteristics of JSF patients and SFTS patients comprehensively, we found that APTT and procalcitonin levels may be valuable in assisting in the identification of SFTS and JSF. In all areas where tick-borne diseases are endemic, include SFTS-epidemic areas, we recommend using the Weil-Felix test to screen for potential rickettsiosis in patients presenting with fever and thrombocytopenia with or without rash in primary healthcare settings, as well as simultaneous testing for the SFTS virus and spotted fever group rickettsioses sequence. Additionally, mNGS sequencing should be used to confirm the diagnosis and provide information for epidemiological investigations in patients who are suspected of having spotted fever group rickettsiosis.

Objectives: Nausea and vomiting in pregnancy (NVP) is a common condition that reduces the quality of life by negatively affecting work and family life, physical and mental health, and economic wellbeing. However, its risk factors remain unclear. This study aimed to explore the association between NVP and verbal rating scale (VRS)-measured dysmenorrhea and to explore potential protective factors. Methods: This retrospective cohort study was conducted from June 2018 to December 2020 at Tongji Hospital in Wuhan. Information on baseline characteristics, pregnancy-related history, periconceptional micronutrient supplementation, and obstetric outcomes were collected. The severity of dysmenorrhea was assessed using VRS. Results: A total of 443 pregnant women were recruited and divided into the NVP group (n = 76) and the control group (n = 367). A significant association was observed between NVP and VRSmeasured dysmenorrhea (c2=10.038, P = 0.007). After adjusting for covariates, the association between moderate/severe dysmenorrhea and NVP remained significant (OR 2.384; 95% CI 1.104-5.148, P = 0.004). First-trimester docosahexaenoic acid supplement (OR 0.443; 95% CI 0.205-0.960, P = 0.039) may be beneficial in reducing the risk of NVP. Conclusions: Women with moderate to severe dysmenorrhea have a higher risk of experiencing NVP during the first trimester. Periconceptional docosahexaenoic acid supplementation may play a protective role.

BackgroundHypoxia in the tumor microenvironment (TME) plays a pivotal role in the progression and prognosis of colorectal cancer (CRC). However, effective methods for assessing TME hypoxia remain lacking. This study aims to develop a novel hypoxia-related prognostic score (HPS) based on hypoxia-associated genes to improve CRC prognostication and inform treatment strategies.MethodsTranscriptomic data from CRC patients were analyzed using Lasso regression to identify hypoxia-associated genes with the strongest prognostic significance. The identified genes were validated in vitro by assessing their expression under normoxic and hypoxic conditions in normal intestinal epithelial cells and CRC tumor cell lines. Functional relevance was explored through differential gene expression analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and protein-protein interaction (PPI) network construction. The association of HPS with extracellular matrix (ECM) composition, immune cell infiltration, and immune suppression was also investigated.ResultsSeven hypoxia-associated signature genes were identified, each demonstrating a strong correlation with CRC prognosis. The hypoxia-related prognostic score (HPS), derived from these genes, was significantly linked to changes in the TME. Specifically, HPS values were associated with alterations in ECM composition and distinct immune cell infiltration patterns. Higher HPS values corresponded to increased infiltration of immune-suppressive cells and reduced presence of anti-tumor immune cells. This imbalance promoted an immune-suppressive TME, facilitating tumor progression and immune evasion.ConclusionsThe hypoxia-related prognostic score (HPS) captures the regulatory influence of TME hypoxia on immune responses, offering valuable insights into its role in tumor progression. HPS holds promise as a prognostic tool and a guide for developing personalized treatment strategies in CRC.