Background Air pollution exposure has a significant impact on maternal and child health. However, the research on the association between ambient ozone (O₃) exposure during pregnancy and the risk of premature birth in newborns is limited, and the conclusions are inconsistent. Objective To investigate the association of ambient O₃ exposure during pregnancy with the risk of preterm birth in Guangdong Province. Methods Data of pregnant women in Guangzhou from 2013 to 2019 and Foshan from 2018 to 2023 were collected, and O₃ concentrations during different trimesters were assessed according to maternal residential addresses. Bilinear interpolation was used to evaluate the concentrations of air pollution. A cohort study design was adopted in our study. Restricted cubic spline curves were used to evaluate the exposure-response relationship between O₃ exposure and preterm birth risk and explore potential exposure threshold of O₃. Logistic regression models were used to evaluate the association of O₃ exposure with preterm birth. Results A total of 702 924 pregnant women were included in this study, of whom 43 051 (6.12%) were preterm. The average O₃ exposure concentrations of pregnant women during the first, second, third, and whole trimesters were 95.51, 97.51, 100.60, and 97.87 μg·m⁻³, respectively. We observed J-shaped associations between O₃ exposure and preterm birth risk during the second, third, and whole trimesters of pregnancy using restricted cubic spline curves. This study found that there were threshold concentrations between O₃ exposure and preterm birth risk during different gestational periods, and the threshold concentrations in the first, second, third, and whole trimesters were 112.32, 99.83, 111.74, and 112.46 μg·m⁻³, respectively. During the second, third, and whole trimesters of pregnancy, after adjusting for maternal age, baby sex, pre-pregnancy body mass index, mode of delivery, baby birth weight, gestational diabetes, and gestational hypertension, the odds ratios (OR) of preterm birth were 1.02 (95%CI: 1.01, 1.04), 1.02 (95%CI: 1.00, 1.03), and 1.17 (95%CI: 1.13, 1.21) for each 10 μg·m⁻³ increase in O₃ concentration above the O₃ threshold. No significant association was found between O₃ exposure and the risk of preterm birth during the first trimester. Conclusion There is a nonlinear association between the risk of preterm birth and O₃ exposure during pregnancy, and higher concentrations of O₃ exposure during pregnancy are associated with the risk of preterm birth. Above the O₃ threshold concentration during pregnancy, especially during the second, third, and whole trimesters, the risk of preterm birth elevates with the increase of O₃ exposure concentrations.

ObjectiveTo establish a method for the identification of Haliotidis Concha and its counterfeits， and to improve its quality evaluation method. MethodsA total of 17 batches of Haliotis discus hannai， 4 batches of H. ruber， 3 batches of H. laevigata， 3 batches of H. ovina， 3 batches of H. diversicolor， 3 batches of H. asinina， 3 batches of H. iris were collected. Ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive-Orbitrap-MS/MS） was used to analyze the hydrolysates of different original Haliotidis Concha and its counterfeits， and the potential characteristic ions of each species were screened by Venn diagram. UPLC-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS/MS） was used to validate the characteristic ions， and the specific detection method of the characteristic ions was established. ResultsA total of 1 182， 167， 47， 89， 104， 203， 424 potential characteristic ions were screened from H. discus hannai， H. ruber， H. laevigata， H. ovina， H. diversicolor， H. asinina and H. iris， respectively. And 9 characteristic ions were selected. The precision， stability and repeatability of the 9 characteristic ions in the established identification method met the requirements. Different original Haliotidis Concha and its counterfeits could detect their own characteristic ions， including m/z 631.83-886.48（double charge） and m/z 631.83-443.74（double charge） of H. discus hannai， m/z 699.28-232.11（double charge） and m/z 699.28-544.27（double charge） of H. ruber， m/z 535.76-752.37（double charge） and m/z 535.76-548.28（double charge） of H. laevigata， m/z 708.35-442.28（double charge） and m/z 708.35-215.14（double charge） of H. ovina， m/z 561.33-614.86（triple charge）， m/z 561.33-468.28（triple charge）， m/z 608.29-618.32（double charge） and m/z 608.29-390.21（double charge） of H. diversicolor， m/z 769.85-274.10（double charge）， m/z 769.85-532.75（double charge）， m/z 827.43-646.36（single charge）， m/z 827.43-257.12（single charge） of H. asinina， and m/z 468.24-576.29（double charge） and m/z 468.24-505.26（double charge） of H. iris. ConclusionIn this study， a total of 9 characteristic ions are screened from 6 kinds of original Haliotidis Concha and its counterfeits， and a specific identification method is established， which is helpful to solve the limitations of the existing quality evaluation methods of Haliotidis Concha， and provide a basis for the production， circulation and medication quality.

ObjectiveTo establish a method for the identification of Haliotidis Concha and its counterfeits， and to improve its quality evaluation method. MethodsA total of 17 batches of Haliotis discus hannai， 4 batches of H. ruber， 3 batches of H. laevigata， 3 batches of H. ovina， 3 batches of H. diversicolor， 3 batches of H. asinina， 3 batches of H. iris were collected. Ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive-Orbitrap-MS/MS） was used to analyze the hydrolysates of different original Haliotidis Concha and its counterfeits， and the potential characteristic ions of each species were screened by Venn diagram. UPLC-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS/MS） was used to validate the characteristic ions， and the specific detection method of the characteristic ions was established. ResultsA total of 1 182， 167， 47， 89， 104， 203， 424 potential characteristic ions were screened from H. discus hannai， H. ruber， H. laevigata， H. ovina， H. diversicolor， H. asinina and H. iris， respectively. And 9 characteristic ions were selected. The precision， stability and repeatability of the 9 characteristic ions in the established identification method met the requirements. Different original Haliotidis Concha and its counterfeits could detect their own characteristic ions， including m/z 631.83-886.48（double charge） and m/z 631.83-443.74（double charge） of H. discus hannai， m/z 699.28-232.11（double charge） and m/z 699.28-544.27（double charge） of H. ruber， m/z 535.76-752.37（double charge） and m/z 535.76-548.28（double charge） of H. laevigata， m/z 708.35-442.28（double charge） and m/z 708.35-215.14（double charge） of H. ovina， m/z 561.33-614.86（triple charge）， m/z 561.33-468.28（triple charge）， m/z 608.29-618.32（double charge） and m/z 608.29-390.21（double charge） of H. diversicolor， m/z 769.85-274.10（double charge）， m/z 769.85-532.75（double charge）， m/z 827.43-646.36（single charge）， m/z 827.43-257.12（single charge） of H. asinina， and m/z 468.24-576.29（double charge） and m/z 468.24-505.26（double charge） of H. iris. ConclusionIn this study， a total of 9 characteristic ions are screened from 6 kinds of original Haliotidis Concha and its counterfeits， and a specific identification method is established， which is helpful to solve the limitations of the existing quality evaluation methods of Haliotidis Concha， and provide a basis for the production， circulation and medication quality.

Objective To investigate the effects and mechanisms of silica dust on the apoptosis of alveolar epithelial cell (AEC) through in vitro and animal experiments. Methods i) In vitro experiment. A549 cells were stimulated with 100 mg/L silica suspension for 0, 12, 24 and 48 hours. The cell apoptosis rate was detected by flow cytometry. ii) Animal experiment. Specific pathogen-free male C57BL/6 mice were randomly divided into control, 14-day, 28-day, and 56-day groups, with five mice in each group. The mice in the control group were sacrificed at 56 days after being treated with 40.0 μL 0.9% sodium chloride solution, and the mice in the last three groups were sacrificed at 14, 28 and 56 days after being treated with 40.0 μL silica suspension with a mass concentration of 125 g/L via tracheal exposure method. The lung tissues of mice were collected to measure lung organ coefficients. Masson staining was used to detect the degree of pulmonary fibrosis, and Ashcroft scores were evaluated. The apoptosis of AEC in mice was observed by TUNEL immunofluorescence assay. iii) The mRNA relative expression of apoptosis-related genes in A549 cells and mouse lung tissue was detected using reverse transcription and real-time fluorescence quantitative polymerase chain reaction. Results i) In vitro experiment. The apoptosis rate of A549 cells increased with longer silica exposure (all P<0.05). The relative expression of B cell lymphoma-2 (BCL-2) mRNA in A549 cells in 24 h group and 48 h group decreased (both P<0.05), and the relative expression of BCL-2 associated X protein (BAX) mRNA increased (both P<0.05), compared with 0 h group. The mRNA relative expression of caspase (CASP) -3 and CASP-9 in A549 cells increased with longer silica exposure (all P<0.05). ii) Animal experiment. The lung organ coefficients and Ashcroft score in mice progressively increased (all P<0.05), the degree of pulmonary fibrosis was gradually aggravated, and TUNEL positive cells in lung tissue were gradually increased, while Bax, Casp-3 and Casp-9 mRNA relative expression increased with longer silica exposure (all P<0.05). Conclusion Silica dust may cause pulmonary fibrosis by inducing apoptosis of AEC, with a time-dependent effect. The mechanism may be related to the effect of silica dust on mitochondrial apoptosis through Bcl-2/Bax/Caspase-3 signaling pathway.

Objective To investigate the protective effects and mechanisms of sulodexide on renal fibrosis induced by prolonged warm ischemia. Methods An in vivo ischemia-reperfusion injury (IRI) model was established in rats, which were randomly divided into Sham group, IRI 60 min group (IRI group), and IRI 60 min + sulodexide group (IRI+SDX group), with 20 rats in each group. Pathological examination was used to evaluate renal tissue injury and fibrosis levels in each group. Immunohistochemistry was performed to detect the expression levels of kidney injury molecule (KIM)-1, intercellular adhesion molecule (ICAM)-1, von Willebrand factor (vWF), transforming growth factor (TGF)-β, α-smooth muscle actin (SMA), and type I collagen (COL-1). Immunofluorescence staining was used to detect CD31 expression. Real-time quantitative polymerase chain reaction was employed to measure the expression of KIM-1, ICAM-1, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in renal tissues. Transmission electron microscopy was used to observe the structure of the renal glycocalyx. Evans blue dye was injected to assess renal vascular permeability. Rat survival was recorded, and serum levels of syndecan (SDC)-1, heparan sulfate (HS) and serum creatinine were measured. An ex vivo perfusion model was also established, with rats randomly assigned to either the hypothermic oxygenated machine perfusion (HOPE) group or the HOPE+SDX group (five rats per group). Perfusion parameters were recorded after 2 hours of ex vivo perfusion. Results One day after reperfusion, compared with the Sham group, the IRI group exhibited more severe renal tissue injury, higher tubular injury scores, increased expression of KIM-1, ICAM-1 and vWF, decreased CD31 expression, elevated serum levels of SDC-1 and HS, increased vascular permeability, and higher expression of TNF-α, IL-1β and IL-6. Compared with the IRI group, the IRI+SDX group showed reduced renal tissue injury, lower tubular injury scores, decreased expression of KIM-1, ICAM-1 and vWF, increased CD31 expression, lower serum levels of SDC-1 and HS, decreased vascular permeability, and reduced expression of TNF-α, IL-1β and IL-6 (all P < 0.05). Ten days after reperfusion, renal tissue injury was further alleviated in the IRI+SDX group. Twenty-five days after reperfusion, the IRI+SDX group exhibited decreased expression of TGF-β, α-SMA, and COL-1, as well as reduced collagen deposition area (all P < 0.05). Compared with the HOPE group, the HOPE+SDX group showed increased renal perfusion flow and decreased intrarenal vascular resistance (both P < 0.01). Conclusions Sulodexide may alleviates renal IRI and fibrosis caused by prolonged warm ischemia by inhibiting inflammatory responses and protecting vascular endothelial glycocalyx.

Reproductive system diseases are among the primary contributors to the decline in social fertility rates and the intensification of aging, posing significant threats to both physical and mental health, as well as quality of life. Recent research has revealed the substantial potential of the gut microbiota in improving reproductive system diseases. Under healthy conditions, the gut microbiota maintains a dynamic balance, whereas dysfunction can trigger immune-inflammatory responses, metabolic disorders, and other issues, subsequently leading to reproductive system diseases through the gut-gonadal axis. Reproductive diseases, in turn, can exacerbate gut microbiota imbalance. This article reviews the impact of the gut microbiota and its metabolites on both male and female reproductive systems, analyzing changes in typical gut microorganisms and their metabolites related to reproductive function. The composition, diversity, and metabolites of gut bacteria, such as Bacteroides, Prevotella, and Firmicutes, including short-chain fatty acids, 5-hydroxytryptamine, γ-aminobutyric acid, and bile acids, are closely linked to reproductive function. As reproductive diseases develop, intestinal immune function typically undergoes changes, and the expression levels of immune-related factors, such as Toll-like receptors and inflammatory cytokines (including IL-6, TNF-α, and TGF-β), also vary. The gut microbiota and its metabolites influence reproductive hormones such as estrogen, luteinizing hormone, and testosterone, thereby affecting folliculogenesis and spermatogenesis. Additionally, the metabolism and absorption of vitamins can also impact spermatogenesis through the gut-testis axis. As the relationship between the gut microbiota and reproductive diseases becomes clearer, targeted regulation of the gut microbiota can be employed to address reproductive system issues in both humans and animals. This article discusses the regulation of the gut microbiota and intestinal immune function through microecological preparations, fecal microbiota transplantation, and drug therapy to treat reproductive diseases. Microbial preparations and drug therapy can help maintain the intestinal barrier and reduce chronic inflammation. Fecal microbiota transplantation involves transferring feces from healthy individuals into the recipient’s intestine, enhancing mucosal integrity and increasing microbial diversity. This article also delves into the underlying mechanisms by which the gut microbiota influences reproductive capacity through the gut-gonadal axis and explores the latest research in diagnosing and treating reproductive diseases using gut microbiota. The goal is to restore reproductive capacity by targeting the regulation of the gut microbiota. While the gut microbiota holds promise as a therapeutic target for reproductive diseases, several challenges remain. First, research on the association between gut microbiota and reproductive diseases is insufficient to establish a clear causal relationship, which is essential for proposing effective therapeutic methods targeting the gut microbiota. Second, although gut microbiota metabolites can influence lipid, glucose, and hormone synthesis and metabolism via various signaling pathways—thereby indirectly affecting ovarian and testicular function—more in-depth research is required to understand the direct effects of these metabolites on germ cells or granulosa cells. Lastly, the specific efficacy of gut microbiota in treating reproductive diseases is influenced by multiple factors, necessitating further mechanistic research and clinical studies to validate and optimize treatment regimens.

Objective To investigate the changes in eosinophil counts and the activation of microglial cells in the brain tissues of mice at different stages of Angiostrongylus cantonensis infection, and to examine the role of microglia in regulating the progression of angiostrongyliasis and unravel the possible molecular mechanisms. Methods Fifty BALB/c mice were randomly divided into the control group and the 7-d, 14-d, 21-day and 25-d infection groups, of 10 mice in each group. All mice in infection groups were infected with 30 stage III A. cantonensis larvae by gavage, and animals in the control group was given an equal amount of physiological saline. Five mice were collected from each of infection groups on days 7, 14, 21 d and 25 d post-infection, and 5 mice were collected from the control group on the day of oral gavage. The general and focal functional impairment was scored using the Clark scoring method to assess the degree of mouse neurological impairment. Five mice from each of infection groups were sacrificed on days 7, 14, 21 d and 25 d post-infection, and 5 mice from the control group were sacrificed on the day of oral gavage. Mouse brain tissues were sampled, and the pathological changes of brain tissues were dynamically observed using hematoxylin and eosin (HE) staining. Immunofluorescence staining with eosinophilic cationic protein (ECP) and ionized calcium binding adaptor molecule 1 (Iba1) was used to assess the degree of eosinophil infiltration and the counts of microglial cells in mouse brain tissues in each group, and the morphological parameters of microglial cells (skeleton analysis and fractal analysis) were quantified by using Image J software to determine the morphological changes of microglial cells. In addition, the expression of M1 microglia markers Fcγ receptor III (Fcgr3), Fcγ receptor IIb (Fcgr2b) and CD86 antigen (Cd86), M2 microglia markers Arginase 1 (Arg1), macrophage mannose receptor C-type 1 (Mrc1), chitinase-like 3 (Chil3), and phagocytosis genes myeloid cell triggering receptor expressed on myeloid cells 2 (Trem2), CD68 antigen (Cd68), and apolipoprotein E (Apoe) was quantified using real-time quantitative reverse transcription PCR (RT-qPCR) assay in the mouse cerebral cortex of mice post-infection. Results A large number of A. cantonensis larvae were seen on the mouse meninges surface post-infection, and many neuronal nuclei were crumpled and deeply stained, with a large number of bleeding points in the meninges. The median Clark scores of mouse general functional impairment were 0 (interquartile range, 0), 0 (interquartile range, 0.5), 6 (interquartile range, 1.0), 14 (interquartile range, 8.5) points and 20 (interquartile range, 9.0) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.45, P < 0.01), and the median Clark scores of mouse focal functional impairment were 0 (interquartile range, 0), 2 (interquartile range, 2.5), 7 (interquartile range, 3.0), 18 (interquartile range, 5.0) points and 25 (interquartile range, 6.5) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.72, P < 0.01). The mean scores of mice general and focal functional impairment were all higher in the infection groups than in the control group (all P values < 0.05). Immunofluorescence staining showed a significant difference in the eosinophil counts in mouse brain tissues among the five groups (F = 40.05, P < 0.000 1), and the eosinophil counts were significantly higher in mouse brain tissues in the 14-d (3.08 ± 0.78) and 21-d infection groups (5.97 ± 1.37) than in the control group (1.00 ± 0.28) (both P values < 0.05). Semi-quantitative analysis of microglia immunofluorescence showed a significant difference in the counts of microglial cells among the five groups (F = 17.66, P < 0.000 1), and higher Iba1 levels were detected in mouse brain tissues in 14-d (5.75 ± 1.28), 21-d (6.23 ± 1.89) and 25-d infection groups (3.70 ± 1.30) than in the control group (1.00 ± 0.30) (all P values < 0.05). Skeleton and fractal analyses showed that the branch length [(162.04 ± 34.10) μm vs. (395.37 ± 64.11) μm; t = 5.566, P < 0.05] and fractal dimension of microglial cells (1.30 ± 0.01 vs. 1.41 ± 0.03; t = 5.266, P < 0.05) were reduced in mouse brain tissues in the 21-d infection group relative to the control group. In addition, there were significant differences among the 5 groups in terms of M1 and M2 microglia markers Fcgr3 (F = 48.34, P < 0.05), Fcgr2b (F = 55.46, P < 0.05), Cd86 (F = 24.44, P < 0.05), Arg1 (F = 31.18, P < 0.05), Mrc1 (F = 15.42, P < 0.05) and Chil3 (F = 24.41, P < 0.05), as well as phagocytosis markers Trem2 (F = 21.19, P < 0.05), Cd68 (F = 43.95, P < 0.05) and Apoe (F = 7.12, P < 0.05) in mice brain tissues. Conclusions A. cantonensis infections may induce severe pathological injuries in mouse brain tissues that are characterized by massive eosinophil infiltration and persistent activation of microglia cells, thereby resulting in progressive deterioration of neurological functions.

Purpose: Neuroendocrine prostate cancer (NEPC) represents a particularly aggressive subtype of prostate cancer with a challenging prognosis. The purpose of this investigation is to craft and confirm the reliability of nomograms that can accurately forecast the 1-, 3-, and 5-year overall survival (OS) and cancer-specific survival (CSS) rates for individuals afflicted with NEPC. Materials and Methods: Data pertaining to patients diagnosed with NEPC within the timeframe of 2010 to 2020 was meticulously gathered and examined from the Surveillance, Epidemiology, and End Results Program (SEER). To predict OS and CSS, we devised and authenticated two distinct nomograms, utilizing predictive variables pinpointed through both univariate and multivariate Cox regression analyses. Results: The study encompassed 393 of NEPC patients, who were systematically divided into training and validation cohorts at a 2:1 ratio. Key prognostic factors were isolated, verified, and integrated into the respective nomograms for OS and CSS. The performance metrics, denoted by C-indices, stood at 0.730, 0.735 for the training set, and 0.784, 0.756 for the validation set. The precision and clinical relevance of the nomograms were further corroborated by the analysis of receiver operating characteristic curves, calibration plots, and decision curve analyses. Conclusions The constructed nomograms have demonstrated impressive efficacy in forecasting the 1-, 3-, and 5-year OS and rates for patients with NEPC. Implementing these predictive tools in clinical settings is anticipated to considerably enhance the care and treatment planning for individuals diagnosed with this aggressive form of prostate cancer, thus providing tailored and more precise prognostic assessments.

Background/Aims: Reflux symptoms frequently present in patients diagnosed with functional dyspepsia (FD). This investigation sought to elucidate the contribution of gastroesophageal reflux in the overlap relationship. Methods: Consecutive patients presenting with reflux symptoms and/or FD symptoms were prospectively included. Comprehensive assessments, including symptoms evaluation, endoscopy, esophageal functional examinations (high-resolution manometry and reflux monitoring), and proton pump inhibitor (PPI) treatment efficacy evaluation, were conducted in these patients. Results: The study enrolled 315 patients, 43.2% of which had concurrent FD symptoms and overlapping reflux symptoms. Notably, a mere 28.7% of patients in the overlap symptoms group had objective gastroesophageal reflux disease evidences (the grade of esophagitis≥ B or the acid exposure time ≥ 4.2%). Functional heartburn was demonstrated to be the main cause of overlapping reflux symptoms(55.1%). Reflux parameters analysis revealed that the reflux burden in the overlap symptoms group paralleled that of the FD symptoms group, with both registering lower levels than the reflux symptoms group (P < 0.05). Furthermore, PPI response rates were notably diminished in the overlap symptoms group (P < 0.001), even for those with objective gastroesophageal reflux disease evidences. Conclusions The study illuminated that overlapping reflux symptoms in FD was common. Strikingly, these symptoms primarily diverged from reflux etiology and exhibited suboptimal responses to PPI intervention. These findings challenge prevailing paradigms and accentuate the imperative for nuanced therapeutic approaches tailored to the distinctive characteristics of overlapping reflux symptoms in the context of FD.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.