To investigate the association of urinary phthalate metabolites with 4 high-density lipoprotein-cholesterol(HDL-C)-related inflammatory indicators [lymphocyte/HDL-C ratio (LHR), monocyte/HDL-C ratio (MHR), neutrophil/HDL-C ratio (NHR), and platelet/HDL-C ratio (PHR)], and to explain their possible biological mechanisms.

The 4 573 adult participants from the National Health and Nutrition Examination Survey (NHANES) were subjected, and then generalized linear regression (GLM), restricted cubic spline (RCS), and weighted quantile sum (WQS) regressions were performed to explore the potential associations of phthalates mono-exposures and mixed exposures, respectively, with the HDL-C-related inflammation metrics.

Nine urinary phthalate metabolites were significantly positively associated with at least 1 inflammatory marker, while 1 metabolite (MEP) showed a negative association with an inflammatory indicator (LHR). Some exposure metabolites showed a nonlinear association with outcome inflammatory indicators. WQS regression revealed varying weight contributions of individual metabolite to each inflammatory outcome. Subgroup analyses indicated differential association effects of phthalates with HDL-C-related inflammatory metrics across gender, age, and BMI populations.

There are associations between phthalate exposure and HDL-C-related inflammation indicators, but further studies are needed to reveal the underlying mechanisms.

To investigate the predictive value of preoperative systemic inflammatory response index (SIRI) combined with clinicopathological parameters for postoperative recurrence in cervical cancer and to construct a prognostic model in order to optimize recurrence risk assessment.

Patients with cervical cancer who underwent standard surgical treatment at the First Affiliated Hospital of Chongqing Medical University (training cohort, n=996) and Chongqing Maternal and Child Health Hospital (validation cohort, n=496) between January 2017 and January 2022 were retrospectively enrolled based on our strict inclusion and exclusion criteria. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors for recurrence-free survival (RFS), and then a nomogram was constructed. Receiver operating characteristic (ROC) curve was plotted to assess the predictive performance of the model, and the area under the curve (AUC) and calibration curve were employed to evaluate the model. Kaplan-Meier survival analysis was performed to determine the clinical application.

Cox regression analysis demonstrated that International Federation of Gynecology and Obstetrics (FIGO) stage (P<0.001), tumor size (P<0.001), pathological type (P<0.001), tumor grade (P=0.007), parametrial invasion (P<0.001), depth of myometrial invasion (P=0.019), lymphovascular space invasion (P=0.019), vaginal margin involvement (P=0.010), adjuvant therapy (P=0.012), and SIRI (P<0.001) were independent prognostic factors for RFS. Our nomogram model based on above prognostic factors exhibited superior predictive performance for 1-, 3-, and 5-year RFS, with a significantly higher AUC value (0.886) than those of single-parameter models.

Our nomogram model demonstrated good accuracy in predicting RFS in cervical cancer patients, providing a potential tool for personalized clinical decision-making in recurrence risk management.

To investigate the bidirectional causal relationship between different subtypes of endometriosis and female infertility using Mendelian randomization (MR).

A two-sample MR analysis was performed on the data sourced from publicly available genome-wide association study (GWAS) of endometriosis and infertility. For each subtype of endometriosis, instrumental variables (IVs) satisfying MR assumptions were selected, with inverse variance weighting (IVW) as primary method. Sensitivity analyses, including Cochran’s Q test, MR-Egger regression, and leave-one-out analysis, were conducted to verify the robustness of the results. Statistical significance was set at P<0.01 (Bonferroni correction), and P<0.05 was considered as suggestive significance.

Among different locations of endometriosis, ovary (IVW: OR=1.26, 95%CI: 1.17~1.35, P<0.001), pelvic peritoneum (IVW: OR=1.26, 95%CI: 1.20~1.33, P<0.001), rectovaginal septum (IVW: OR=1.11, 95%CI: 1.06~1.16, P<0.001), adenomyosis (IVW: OR=1.16, 95%CI: 1.07~1.25, P<0.001), and other types of endometriosis (IVW: OR=1.10, 95%CI: 1.03~1.17, P=0.004) were significantly associated with infertility. But no such association was observed in fallopian tube and intestinal endometriosis with infertility (P>0.05). Reverse causality analysis indicated that infertility might lead to fallopian tube endometriosis (IVW: OR=1.46, 95%CI: 1.11~1.93, P=0.007), and was associated with ovarian (IVW: OR=1.56, 95%CI: 1.27~1.93, P<0.001), pelvic peritoneal (IVW: OR=1.34, 95%CI: 1.11~1.62, P=0.003), rectovaginal (IVW: OR=1.46, 95%CI: 1.11~1.93, P=0.007), and other types of endometriosis (IVW: OR=1.61, 95%CI: 1.21~2.13, P=0.001). Suggestive significance was observed statistically in infertility promoting adenomyosis (IVW: OR=1.16, 95%CI: 1.07~1.25, P<0.05). It had not been proven yet that infertility could lead to intestinal endometriosis (P>0.05). Sensitivity analyses confirmed the robustness of the results.

Bidirectional causal relationships exist between different subtypes of endometriosis and infertility. Our findings based on MR analysis validate the clinical observation that endometriosis can lead to infertility, and we exploratively propose an important conclusion that infertility itself may also induce endometriosis. However, due to limited data, the causal relationships between intestinal/tubal endometriosis and infertility require further investigation.

To identify risk factors for postoperative respiratory failure (PORF) in cardiovascular surgery patients using machine learning algorithms and to construct a specific risk prediction model.

A retrospective cohort was conducted on 1 623 patients undergoing cardiovascular surgery between 2011 and 2020 from the INSPIRE database. Following data quality analysis, multiple imputation was employed to handle missing data, and the Boruta algorithm was used for feature selection. Eight machine learning models were constructed based on the selected features, including Gradient Boosting Machine (GBM), Generalized Linear Model (GLM), Extreme Gradient Boosting (XGBoost), K-Nearest Neighbors (KNN), Neural Network (NNET), Naive Bayes (NB), Support Vector Machine (SVM), and Random Forest (RF). Model performance was evaluated using metrics including the area under the curve (AUC), sensitivity, and specificity. Variables significantly influencing PORF were identified using the permutation importance algorithm.

The overall incidence of PORF was 27.05% (439/1 623). The in-hospital mortality rate was significantly higher in the PORF group than the non-PORF group (12.98% vs 1.60%, P<0.001). Among the developed models, the SVM model demonstrated the best performance, achieving an AUC of 0.705 in the testing set, with a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 0.481, 0.825, 0.504, and 0.812, respectively. Based on feature importance analysis, the top 10 variables most predictive of PORF were anesthesia duration, arterial partial pressure of carbon dioxide (PaCO₂), calcium level, lymphocyte percentage, cardiopulmonary bypass duration, intraoperative blood loss, age, creatinine level, aspartate aminotransferase (AST) level, and activated partial thromboplastin time (aPTT).

A predictieon model for PORF following cardiovascular surgery is successfully developed. This model can identify high-risk patients and estimate their probability of developing respiratory failure, thereby facilitating data-driven clinical decision-making.

To investigate the mechanism by which peripubertal exposure to di-2-ethylhexyl phthalate （DEHP） induces reproductive injury in adult male mice through impairment of Sertoli cell function and the blood-testis barrier.

A total of 180 male C57BL/6J mice （3 weeks old） were randomly divided into corn oil group （control group），and 5，25，125，250 and 500 mg/kg DEHP exposure groups. All groups received daily oral gavage for 5 consecutive weeks. Ten mice from each group were sacrificed for first material collection when they were 9 weeks old. The remaining F0 generation mice were mated with unexposed adult female mice at a male-to-female ratio of 1∶2 at 14 weeks of age for a period of 2 weeks. The second material collection was completed at 16 weeks of age，with 20 mice taken from each group. A computer-assisted analysis system was used to detect sperm density and motility in 9-week-old and 16-week-old male mice. The average birth body weight of F1 generation pups，survival rate of pups at 4 d after birth per litter，number of pups per litter，and male-to-female sex ratio within the litter were recorded. ELISA was used to detect hormone levels in the serum. Sperm abnormalities were observed using eosin staining. HE staining was used to observe pathological changes in testicular tissue. Immunofluorescence assay was utilized to detect the protein expression of tight junction protein 1 （zonula occludens-1，ZO-1） and gap junction protein 43 （connexin43，Cx43） related to the blood-testis barrier in testicular tissue，as well as the protein expression of apoptosis-related molecule Cleaved-Caspase3. Immunohistochemistry was used to detect the expression of Sertoli cell marker SOX9 protein in testicular tissue. TUNEL was used to detect apoptosis in testicular tissue. Comparative toxicogenomics database （CTD） was used to screen for mono-2-ethylhexyl phthalate （MEHP） induced reproductive damage-associated genes and combined with GO/KEGG and Reactome enrichment analysis to predict possible signaling pathways. An in vitro exposure model was established by treating TM4 cells with MEHP at concentrations of 0，50，100，200 and 400 μmol/L，respectively. CCK-8 assay，flow cytometry and Western blotting were applied to detect the cell viability，apoptosis，and protein expression of apoptosis-related proteins B-cell lymphoma 2 （Bcl-2） and Bcl-2-associated X protein （Bax），and blood-testis barrier-related proteins ZO-1 and Cx43.

Compared with the control group，the pregnancy rate was decreased from 80.0% to 52.5%，and the total number of pups was decreased from 212 to 125 in the female mice mating with the male from the 500 mg/kg group. Compared with the control group，the sperm density and motility were significantly reduced，and the total rate of sperm abnormalities was obviously increased in the 9-week-old DEHP-exposed mice （P<0.05），and even in the 16-week-old mice，the sperm motility was still in a dose-dependent downward trend （P<0.05）. In the 25，125，250 and 500 mg/kg DEHP exposure groups，the thickness of the seminiferous epithelium was obviously decreased，with more cellular vacuolization and notable epithelial atrophy and degeneration. Cell apoptosis in the testicular tissue was enhanced，while the expression of ZO-1 and Cx43 were decreased in the 250 and 500 mg/kg exposure groups. The levels of androgen-binding protein，gonadotropin-releasing hormone，and testosterone in the serum were decreased in a dose-dependent manner （P<0.05），while those of luteinizing hormone and follicle-stimulating hormone showed a dose-dependent increase （P<0.05）. Bioinformatics analysis showed that 153 genes related to male system diseases were screened out by CTD for MEHP. GO enrichment，KEGG pathway，and Reactome enrichment analyses displayed that the apoptosis signaling pathway was significantly enriched. CCK-8 assay showed that TM4 cell viability was decreased in a dose-dependent manner after MEHP treatment when compared with the control group （P<0.05）. Western blotting indicated that MEHP treatment reduced the expression levels of Bcl-2，ZO-1 and Cx43 （P<0.05），and enhanced that of Bax in comparison with the control group （P<0.05）.

Peripubertal DEHP exposure may lead to reduced sperm quality and reproductive damage in adult male mice by disrupting the blood-testis barrier and activating Sertoli cell apoptosis.

To investigate the effects and potential mechanisms of polystyrene micro/nanoplastics (PS-MNPs) on testicular Sertoli cells.

Sixty male C57BL/6N mice (8 weeks old) were randomly divided into a control group (deionized water), a PS-NPs group [particle size of 20 nm, 2.5 mg/(kg·d)], and a PS-MPs group [particle size of 5 μm, 2.5 mg/(kg·d)], with 20 mice in each group. The corresponding agents were gavaged once daily for 6 months. HE staining was used to observe the histopathological and morphological changes in the testicular tissues. Immunohistochemistry of marker proteins was employed to evaluate the changes in the number of Sertoli cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to identify functions and signaling pathways enriched in the testicular transcriptome. Mouse testicular Sertoli cell line TM4 was divided into a control group (deionized water), a 2.5NPs group (2.5 μg/mL), and a 2.5MPs group (2.5 μg/mL). All groups received continuous exposure through 130 cell passages. Cell viability and proliferative capacity were evaluated using CCK-8 assay and EdU incorporation, while cell migration was assessed using transwell and cell scratch assays. RT-qPCR and Western blotting were used to detect the changes in the expression of key molecules regulating mesenchymal phenotypic transformation (MPT) at mRNA and protein levels.

Pathological analysis revealed that, when compared to the control group, PS-NPs and PS-MPs treatment resulted in extended spaces between testicular seminiferous tubules, loosely arranged spermatogenic cells, and enhanced vacuolization. Immunohistochemical analysis of marker proteins indicated a decreasing trend in the number of testicular Sertoli cells in the PS-NPs and PS-MPs groups than the control group, with the PS-NPs group having statistical significance (P<0.01). GO and KEGG enrichment analyses revealed that PS-MNPs exposure-related altered genes were significantly enriched in cell adhesion signaling pathways (P<0.05). PS-MPs exposure significantly inhibited the growth and migration ability of TM4 cells (P<0.05), but PS-NPs exposure had no such effect on cell growth but notably enhanced cell migration ability. PS-NPs exposure inhibited the expression levels of E-cadherin and ZO-1 (P<0.01) and up-regulated the expression of N-cadherin and vimentin (P<0.01), and PS-MPs exposure led to significant up-regulation of vimentin (P<0.01) and down-regulation of E-cadherin, N-cadherin, and ZO-1 (P<0.05). Both PS-MPs and PS-NPs exposure up-regulated the mRNA levels of Snail2, Twist1, and Zeb2 (P<0.01).

Exposure of PS-MNPs leads to abnormal proliferation and migration of TM4 cells, induces decreases in cell-cell contacts among Sertoli cells and spermatogenic cells at all levels possibly through MPT, and thus results in testicular damage.

To investigate whether long-term low-dose exposure to polystyrene microplastics (PS-MPs) induces ferroptosis in testicular Sertoli cells and then leads to testicular injury.

Forty 8-week-old male C57BL/6 mice were randomly divided into a control group (deionized water group) and a PS-MPs group [2.5 mg/(kg·d)], with 20 mice in each group. Corresponding agents were gavaged once a day for 12 consecutive months. HE staining and Prussian blue staining were used to detect histopathological damage and accumulation of ferrous ions in the testes. Electron transmission microscopy was employed to observe the mitochondrial morphology of testicular Sertoli cells. Mouse Sertoli cell line TM4 was divided into a Con group (standard culture) and an MPs group (2.5 μg/mL PS-MPs). After both groups underwent continuous exposure and passed up to the 100th generation, morphological changes were observed under the microscope; cell viability was detected with CCK8 assay, and production of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected with a ROS probe and a mitochondrial membrane potential probe (JC-1), respectively. Flow cytometry, ferrous ion (Fe²⁺) kit and Western blotting were applied to detect cell apoptosis, intracellular iron ion content, and protein levels of key molecules of ferroptosis in tissues and cells.

Long-term exposure to PS-MPs resulted in significantly reduced diameter and thickness of mouse varicocele (P<0.01), fewer testicular Sertoli cells (P<0.05), with characteristic ferroptosis alterations in the mitochondria, and increased accumulation of ferrous ions in testicular tissue. Exposure to PS-MPs down-regulated the key molecules of ferroptosis, glutathione peroxidase 4 （GPX4） and ferritin light chain （FTL） when compared with the control group (P<0.05). In the cell model, long-term PS-MPs exposure led to morphological changes and decreased cell viability (P<0.05), more production of ROS (P<0.01), and decrease in MMP (P<0.05) of TM4 cells. The exposure had no effect on cell apoptosis, but elevated the intracellular content of ferric ions (P<0.01), and down-regulated GPX4 and FTL protein levels (P<0.05).

Long-term low-dose exposure to PS-MPs induces mitochondrial damage and oxidative stress in testicular Sertoli cells, activates the ferroptosis pathway, and ultimately leads to testicular injury in mice.

To analyze the detrimental effects of exposure to environmental noise alone and combined with carbon monoxide (CO) on spermatogenesis in male rats, investigate the underlying mechanisms involved in such damage, and evaluate the protective role of pterostilbene (PTE) against these adverse effects.

Sixty male SD rats (6~8 weeks old, weighing 200±10 g) were randomly divided normal control group (standard housing), sham-exposure control group (restraint stress only), noise exposure (85 dB), CO exposure (460 mg/m³), combined exposure (simultaneous exposure), and PTE intervention (80 mg/kg pretreatment), with 10 animals in each group. The rats were exposed daily for 2 h via a nose-only inhalation exposure system within a multifactorial environmental simulation chamber for 60 consecutive days. Sperm count and viability were measured after exposure. Histopathological changes of testicular tissues were observed with HE staining. qRT-PCR was used to measure stage-specific mRNA levels in germ cells. Serum sex hormone levels and adenosine triphosphate (ATP) concentrations in testes and sperm were detected. Transmission electron microscopy (TEM) was applied to observe the ultrastructural damage in the spermatocytes. Additionally, transcriptome sequencing was performed on testicular tissue, followed by bioinformatics analysis.

Compared with the negative control group, the combined exposure group exhibited significant reductions in sperm viability and count (P<0.05), and developmental arrest of immature germ cells in the testicular tissue, with obviously less spermatogonia, spermatocytes, and round/elongated spermatids (P<0.01). Additionally, significantly reduced levels of reproductive-related hormones, such as gonadotropin-releasing hormone, follicle-stimulating hormone, luteinizing hormone and testosterone, and ATP levels in testes and sperm were observed in the mice after combined exposure (P<0.01), accompanied by mitochondrial rupture and cristae disruption in spermatocytes. Conversely, the PTE intervention group showed marked alleviation of these impairments, with parameters recovering almost to normal levels. Transcriptome sequencing identified biological processes related to reproductive development and ATP-dependent pathways as potential contributors to testicular injury induced by noise and CO exposure, with key genes including Nppa, Adm, Gnrh1, Ptafr, Atp13a5, Atp8b1, and LOC102555469.

Noise and CO exposure induce spermatogenic damage in rats, which may be related with energy metabolism and hormonal regulation, while PTE demonstrates significant protective effects against such reproductive impairments.

To investigate the transgenerational effects of paternal PM_2.5 exposure on offspring growth and development, and to preliminarily elucidate the role of sperm DNA methylation modifications in mediating these effects.

Eight-week-old male C57BL/6 mice were randomly divided into filtered air (FA), unfiltered air (UA), and concentrated PM_2.5 (CAP) groups, with 10 animals in each group. The exposure was conducted from November 2019 to April 2020, and then, these male mice were mated with unexposed females to generate F1 offspring, which were bred successively to produce F2 and F3 generations. All the offspring were living in PM_2.5-free environment. The birth body weight, birth number, and sex ratio of the offspring were recorded, body weight growth was monitored, and organ coefficients of the heart, liver, lung, and brain were calculated. Whole-genome methylation sequencing was performed on the sperm DNA of the CAP group, FA group, and their F1 generation offspring to screen for differentially methylated regions, and the genes and pathways associated with these regions were analyzed.

When compared with the F1~F3 offspring of the FA group, the CAP group had significantly reduced birth body weight in the F1 generation (P<0.05), no statistical differences were observed in the birth body weight in the F2 and F3 generations (P>0.05), or either in the sex ratio and birth number among the F1, F2 and F3 generations. Compared with the FA group offspring, the F1~F3 offspring of CAP group exhibited delayed body weight gain, especially in the males (P<0.05), the CAP-F1 male generation had obviously elevated liver organ coefficient (P<0.01), but no statistical changes were observed in the heart, lung, or brain coefficients among the F1~F3 generations. Between the FA group and the CAP group, 37 997 differentially methylated regions were detected, with a reduction of approximately 50% in the number of differentially methylated regions in the F1 generation. Differentially methylated genes in F0 and F1 sperm were potentially related to developmental processes, including imprinting genes (Gnas, Igf2) and metabolic genes (Ppard, Rps6kb1).

Paternal exposure to PM_2.5 leads to reduced birth weight and intergenerational growth retardation in offspring. Its impact on phenotypic effects is gradually weakened during intergenerational transmission. Changes in the methylation of development-related genes in sperm may be one of the mechanisms mediating this intergenerational effect.