Objective Objective To analyze the potential spatial factors affecting the genetic differentiation of Oncomelania hupensis robertsoni in Yunnan Province. Methods A total of 13 administrative villages were selected from schistosomiasis-endemic areas of Yunnan Province as O. hupensis snail sampling sites. At least 200 snails were collected in each site, and the spatial variable data of each site were recorded, including longitude, latitude and altitude. Thirty active and Schistosoma japonicum uninfected O. hupensis snails were selected from each sampling site by means of the crawling method and the cercarial shedding method. Genomic DNA was extracted from O. hupensis snails. Following PCR amplification, purification of PCR amplification products and sequencing, the gene sequences of O. hupensis snail samples were spliced and edited using the DNAstar software and the NCBI database to yield the complete mitochondrial sequences of O. hupensis snails at each sampling site, and the mitochondrial genetic distance matrix of O. hupensis robertsoni was calculated at each sampling site. The geographical coordinates of each sampling site were marked using the software ArcGIS 10.2, and the straight-line geographical distance between each sampling site was calculated. The altitude difference, longitude difference and latitude difference between each sampling site were calculated using the Excel software, and the correlation between the mitochondrial genetic distance matrix of O. hupensis robertsoni and each spatial variable matrix was examined by using the Mantel test at 13 sampling sites in Yunnan Province. Results Among the 13 O. hupensis snail sampling sites in Yunnan Province, the largest mitochondrial genetic distance of O. hupensis robertsoni snail populations was seen between Anding Village, Nanjian Yi Autonomous County and Caizhuang Village, Midu County (26.244 2), and the largest geographical distance was seen between Dongyuan Village, Gucheng District and Cangling Village, Chuxiong County (272.64 km). The highest altitude difference was seen between Anding Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1 086.10 m), and the largest longitude difference was found between Qiandian Village, Eryuan County and Cangling Village, Chuxiong County (1.86°), while the largest latitude difference was measured between Leqiu Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1.81°). In addition, the mitochondrial genetic distance of O. hupensis robertsoni snail populations was positively correlated with altitude at 13 snail sampling sites in Yunnan Province (r = 0.542 8, P < 0.001), and showed no significant correlations with geographical distance (r = 0.093 4, P > 0.05), longitude (r = −0.199 5, P > 0.05) or latitude (r = 0.205 7, P > 0.05). Conclusion Altitude may be a potential spatial factor affecting the genetic differentiation of O. hupensis robertsoni in Yunnan Province.

Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

With the continuous deepening of the concept of precision diagnosis and treatment for lung cancer, how to achieve higher efficiency and accuracy in the screening, diagnosis, and treatment pathways in clinical practice has become an important issue that urgently needs to be overcome. The current clinical difficulty lies in the fact that despite continuous advancements in imaging and molecular diagnostic technologies, there are still limitations in manual efficiency and subjective experience when it comes to massive data analysis and multi-scale feature extraction. Artificial intelligence (AI), especially algorithm systems based on deep learning, is an innovative technology capable of deeply empowering medical big data. This method utilizes algorithms such as convolutional neural networks, combined with radiomics, pathomics, and multi-modal data fusion analysis, demonstrating immense potential in early precise detection and benign-malignant differentiation of pulmonary nodules, digital pathological subtype recognition and non-invasive prediction of driver genes, precise 3D surgical planning and automatic delineation of radiotherapy target volumes, as well as dynamic risk warning during follow-up. This innovative technology provides a brand-new solution for realizing intelligent and individualized lung cancer diagnosis and treatment models. This consensus, based on the latest evidence from evidence-based medicine and combined with the development trends in the AI field and real-world clinical needs, was ultimately formed by gathering the consensus opinions of multidisciplinary experts in radiology, pathology, thoracic surgery, and other fields. The main content covers the application specifications of AI in the three core scenarios of lung cancer screening, diagnosis, and treatment, the technical standards for data collection and algorithm validation, as well as the ethical and regulatory challenges faced at the current stage. It aims to clarify the applicable boundaries of AI as a clinical auxiliary decision support tool, providing scientific guidance and standardized exploration directions for peers currently engaged in or planning to carry out AI-assisted clinical diagnosis, treatment, and translation of lung cancer.

Atherosclerosis (AS) remains the core pathological basis underlying the high incidence and high rates of mortality and disability associated with cardiovascular disease (CVD) worldwide. Its essence is not merely lipid deposition, but rather an immune-mediated disease of the vascular wall characterized by an interplay of lipid metabolism disorders and chronic inflammation, with damage to vascular endothelial cells serving as the initiating event. As the disease progresses, it involves complex synergistic interactions among various cellular components, including endothelial cells, macrophages, and inflammatory cells, ultimately leading to plaque formation, instability, and even fatal thrombotic events. In recent years, the central driving role of lipid metabolic reprogramming in the progression of AS has garnered increasing attention from the scientific community. Among the vast array of lipid molecules, long-chain fatty acids (LCFAs) have become a primary focus of research due to their exceptional physiological functions. Traditional views have primarily emphasized the basic physiological functions of LCFAs: serving as highly efficient energy substrates through mitochondrial β-oxidation and acting as key structural components of cellular phospholipid membranes. However, emerging evidence clearly indicates that the functions of LCFAs extend far beyond those of mere metabolic fuel. They also act as potent bioactive signaling molecules, playing an indispensable multidimensional role in the pathogenesis of AS. Equally noteworthy and representing a paradigm shift in cardiovascular research is the emerging theory of the “gut-heart axis”. This theoretical framework views the human gut microbiota—comprising trillions of microorganisms—as a critical and metabolically active “bioreactor”. A wealth of clinical and multi-cohort epidemiological studies have conclusively demonstrated that imbalances in the composition and function of the gut microbiota are highly correlated with the clinical risk and severity of AS. Within this axis, the gut microbiota serves as the primary processing hub for dietary lipids. It actively participates in the digestion and biochemical remodeling of LCFAs, thereby altering their saturation and chemical structure and generating a wide variety of gut microbial metabolites. The effects of these gut-derived lipid metabolites extend far beyond the local intestinal microenvironment. Upon entering the bloodstream, these circulating microbiota metabolites act as endocrine signals. Given the extreme complexity of the underlying mechanisms, a comprehensive elucidation of the synergistic and bidirectional interactions between LCFAs and the gut microbiota in vascular pathology is particularly urgent. Therefore, this article aims to provide a systematic review of the multidimensional regulatory mechanisms of LCFAs and their associated gut microbiota metabolites in the onset, progression, and clinical manifestations of AS. By thoroughly exploring the interaction patterns within the “LCFAs-gut microbiota-AS” triad, this review seeks to fundamentally expand our understanding of the pathogenesis of CVDs. More importantly, translating these mechanistic insights into clinical practice holds tremendous promise. We hope to provide a solid theoretical foundation for the future development of novel AS prevention and treatment strategies based on non-traditional approaches. These include precision nutritional interventions (i.e., dietary lipid intake plans tailored to an individual’s unique microbiome profile) and targeted microbiome modulation therapies (such as next-generation probiotics, prebiotics, or specific metabolite supplements). Targeting the gut as a “reactor” to treat vascular wall lesions represents a promising direction for future cardiovascular medicine.

ObjectiveTo investigate the effects and mechanisms of Fangji Fulingtang （FFD） on mitochondrial function in the mouse model of myocardial fibrosis （MF）. MethodsSixty SPF-grade male C57BL/6J mice were randomly allocated into six groups （n=10 per group）： control， model， low-dose， medium-dose， and high-dose （3.315， 6.63， and 13.26 g·kg^-1， respectively） FFD， and captopril （20 mg·kg^-1）. MF was induced by subcutaneous injection of isoproterenol （10 mg·kg^-1·d^-1） in other groups except the control group for 14 consecutive days， with simultaneous gavage of corresponding drugs. Left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） were measured by echocardiography. Serum levels of creatine kinase-MB （CK-MB）， cardiac troponin I （cTnI）， N-terminal pro-brain natriuretic peptide （NT-pro BNP）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） were determined by enzyme-linked immunosorbent assay （ELISA）. Malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione （GSH） levels were measured by biochemical assays. Reactive oxygen species （ROS） were detected by dihydroethidium （DHE） fluorescence staining. Hematoxylin-eosin （HE）， Masson's trichrome， and wheat germ agglutinin （WGA） staining were performed to evaluate myocardial structure and fibrosis. Mitochondrial ultrastructure and function were assessed by transmission electron microscopy， adenosine triphosphate （ATP） colorimetric assay， and JC-1 fluorescence staining. The protein levels of phosphorylated adenosine monophosphate-activated protein kinase α subunit （p-AMPKα）， AMPKα， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， mitofusin 2 （MFN2）， pyruvate kinase M2 isoform （PKM2）， lactate dehydrogenase A （LDHA）， and hypoxia-inducible factor 1 alpha （HIF-1α） were analyzed by Western blot. ResultsCompared with the control group， the model group exhibited decreased LVEF and LVFS， increased heart weight index and heart weight-to-tibia length ratio （P<0.01）， elevated levels of myocardial injury markers （CK-MB， cTnI， and NT-pro BNP）， inflammatory cytokines （TNF-α， IL-1β， and IL-6）， and MDA， along with reduced SOD and GSH levels （P<0.01）. Enhanced interstitial collagen deposition and cardiomyocyte hypertrophy were observed in the model group （P<0.01）. Transmission electron microscopy and JC-1 staining revealed mitochondrial swelling， crista disruption， decreased ATP content， and reduced red/green fluorescence ratio in the model group （P<0.01）. Western blot analysis demonstrated downregulation of p-AMPKα， PGC-1α， and MFN2 and upregulation of PKM2， LDHA， and HIF-1α in the model group （P<0.01）. Compared with the model group， treatment with FFD or captopril improved LVEF and LVFS， reduced heart weight index and heart weight-to-tibia length ratio （P<0.05， P<0.01）， lowered the serum levels of CK-MB， cTnI， NT-pro BNP， TNF-α， IL-1β， IL-6， and MDA， increased the SOD and GSH levels （P<0.05， P<0.01）， attenuated the myocardial fibrosis and cardiomyocyte hypertrophy （P<0.01）， and restored the mitochondrial ultrastructure. The medium and high-dose FFD groups as well as the captopril group showed increased ATP production and red/green fluorescence ratio （P<0.05， P<0.01）. Furthermore， FFD upregulated the expression of p-AMPKα and PGC-1α while downregulating the expression of LDHA and HIF-1α （P<0.05， P<0.01）. ConclusionFFD activates the AMPK/PGC-1α/MFN2 signaling pathway and inhibits the PKM2/LDHA/HIF-1α axis to restore mitochondrial function and energy metabolic homeostasis， thereby attenuating isoproterenol-induced myocardial fibrosis.

ObjectiveTo investigate the effects and mechanisms of Fangji Fulingtang （FFD） on mitochondrial function in the mouse model of myocardial fibrosis （MF）. MethodsSixty SPF-grade male C57BL/6J mice were randomly allocated into six groups （n=10 per group）： control， model， low-dose， medium-dose， and high-dose （3.315， 6.63， and 13.26 g·kg^-1， respectively） FFD， and captopril （20 mg·kg^-1）. MF was induced by subcutaneous injection of isoproterenol （10 mg·kg^-1·d^-1） in other groups except the control group for 14 consecutive days， with simultaneous gavage of corresponding drugs. Left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） were measured by echocardiography. Serum levels of creatine kinase-MB （CK-MB）， cardiac troponin I （cTnI）， N-terminal pro-brain natriuretic peptide （NT-pro BNP）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） were determined by enzyme-linked immunosorbent assay （ELISA）. Malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione （GSH） levels were measured by biochemical assays. Reactive oxygen species （ROS） were detected by dihydroethidium （DHE） fluorescence staining. Hematoxylin-eosin （HE）， Masson's trichrome， and wheat germ agglutinin （WGA） staining were performed to evaluate myocardial structure and fibrosis. Mitochondrial ultrastructure and function were assessed by transmission electron microscopy， adenosine triphosphate （ATP） colorimetric assay， and JC-1 fluorescence staining. The protein levels of phosphorylated adenosine monophosphate-activated protein kinase α subunit （p-AMPKα）， AMPKα， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， mitofusin 2 （MFN2）， pyruvate kinase M2 isoform （PKM2）， lactate dehydrogenase A （LDHA）， and hypoxia-inducible factor 1 alpha （HIF-1α） were analyzed by Western blot. ResultsCompared with the control group， the model group exhibited decreased LVEF and LVFS， increased heart weight index and heart weight-to-tibia length ratio （P<0.01）， elevated levels of myocardial injury markers （CK-MB， cTnI， and NT-pro BNP）， inflammatory cytokines （TNF-α， IL-1β， and IL-6）， and MDA， along with reduced SOD and GSH levels （P<0.01）. Enhanced interstitial collagen deposition and cardiomyocyte hypertrophy were observed in the model group （P<0.01）. Transmission electron microscopy and JC-1 staining revealed mitochondrial swelling， crista disruption， decreased ATP content， and reduced red/green fluorescence ratio in the model group （P<0.01）. Western blot analysis demonstrated downregulation of p-AMPKα， PGC-1α， and MFN2 and upregulation of PKM2， LDHA， and HIF-1α in the model group （P<0.01）. Compared with the model group， treatment with FFD or captopril improved LVEF and LVFS， reduced heart weight index and heart weight-to-tibia length ratio （P<0.05， P<0.01）， lowered the serum levels of CK-MB， cTnI， NT-pro BNP， TNF-α， IL-1β， IL-6， and MDA， increased the SOD and GSH levels （P<0.05， P<0.01）， attenuated the myocardial fibrosis and cardiomyocyte hypertrophy （P<0.01）， and restored the mitochondrial ultrastructure. The medium and high-dose FFD groups as well as the captopril group showed increased ATP production and red/green fluorescence ratio （P<0.05， P<0.01）. Furthermore， FFD upregulated the expression of p-AMPKα and PGC-1α while downregulating the expression of LDHA and HIF-1α （P<0.05， P<0.01）. ConclusionFFD activates the AMPK/PGC-1α/MFN2 signaling pathway and inhibits the PKM2/LDHA/HIF-1α axis to restore mitochondrial function and energy metabolic homeostasis， thereby attenuating isoproterenol-induced myocardial fibrosis.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

Objective:To explore the relationship between urinary cadmium levels and thyroid hormone levels in people aged 40-89 years old in selected areas of China.Methods:Based on the "Investigation of the Impact of Soil Quality of Agricultural Land on Human Health in Typical Areas" project from October 2019 to August 2020, a multi-stage stratified random sampling method was used to include 6 588 middle-aged and older adults aged 40-89. Demographic characteristics, dietary frequency and disease status were collected through the questionnaire and physical examination. Urinary cadmium and urinary creatinine were detected by random midstream urine. Fasting venous blood was collected for the detection of Triiodothyronine (T3) and Thyroxine (T4). The linear mixed effects model was used to explore the association of urine cadmium levels with thyroid hormone levels. Its dose-response relationship was explored by using the restricted cubic spline.Results:The age of the subjects was (63.48±12.18) years, with males accounting for 51.28%. The M ( Q 1,Q 3) of urinary cadmium level, T3 and T4 was 2.48 (1.36, 4.42) μg/g·creatinine, (1.96±0.51) nmol/L and (113.75±29.11) nmol/L, respectively. The linear mixed effects model showed that the changes of T3 and T4 were 0.027 (0.009, 0.044) nmol/L and 2.019 (1.084, 2.953) nmol/L for each one-unit increase (natural logarithm transformed) of urinary cadmium. The restricted cubic spline showed that there was a positive nonlinear association between urinary cadmium and T3 as well as T4 (all Pnonlinear<0.05). Conclusion:In selected areas of China, the urinary cadmium level of middle-aged and older adults aged 40-89 years is positively associated with T3 and T4.

Objective:To establish 30-day of age transcutaneous bilirubin (TcB) reference curves for healthy neonates, and to investigate regional variations in bilirubin dynamics.Methods:A multicenter retrospective cohort study was conducted. A total of 220 950 healthy neonates born at a gestational age of 35-<42 weeks, with a birth weight ≥2 000 g, who did not receive phototherapy within 60 h after birth were recruited. All of them underwent remote TcB monitoring using the Bilibaby remote jaundice monitoring system between August 1 st, 2020 and December 31 st, 2024 in 426 hospitals. TcB data were collected within the period from birth to 30-day of age. The P40, P75, and P95 of TcB values were calculated, and dynamic TcB curves for 30-day of age were constructed. Patterns of bilirubin change, rates of change, and transition outcomes were described. Regional comparisons between South and North were conducted using linear mixed-effects models for TcB trajectories and Pearson′s chi-square test for outcome differences. Results:A total of 220 950 neonates were included, of whom 101 711 (46.03%) were female. Gestational age at birth was (38.75±1.12) weeks, and birth weight was (3 272±417) g. TcB levels increased rapidly within 3-day of age, peaked at 4-6-day of age, with peak values at P40, P75, and P95 of 200.6, 239.7 and 275.4 μmol/L (11.8, 14.1 and 16.2 mg/dl), respectively. TcB levels gradually declined thereafter and stabilized after 13-day of age, with values at P40, P75, and P95 fluctuating between 147.9-159.8, 190.4-200.6, and 231.2-239.7 μmol/L (8.7-9.4, 11.2-11.8, 13.6-14.1 mg/dl), respectively. Notably, among neonates categorized as low-or low-intermediate-risk within 3-day of age, 6 700 (12.76%) progressed to intermediate-high or high risk between 4 and 30 days of age. Before 13-day of age, TcB levels in the southern regions were consistently higher than those in the northern regions ( P=0.039); from 14 to 30 days of age, the overall TcB levels had no statistically difference, but the temporal changes in TcB still showed regional differences (degrees of freedom=3, all interaction P<0.05). Among neonates classified as low-or low-intermediate risk within 3-day of age, 25 326 were from southern regions, of whom 4 254 (16.80%) progressed to intermediate-high or high risk between 4 and 30 days of age. In northern regions, 27 193 neonates were classified as low-or low-intermediate risk within 3-day of age, among whom 2 446 (8.99%) progressed to intermediate-high or high risk. The risk progression between the 2 regions had statistically difference ( χ2=716.49, P<0.001). Conclusions:A TcB percentile curve for neonates within 30-day of age was established, revealing that both the overall TcB level and its temporal trend were higher in southern than in northern newborns. These findings provide baseline data to support continuous management of neonatal jaundice.