To investigate the effect and mechanisms of celecoxib on right heart function in mice with acute high-altitude hypoxia exposure.

Male C57BL/6J mice (7 weeks old) were housed in a hypobaric chamber simulating an altitude of 5 800 m for 2 d to establish an animal model of acute hypobaric hypoxia. ①Eighteen mice were randomly assigned to plain+saline (P+S), high-altitude hypoxia exposure+saline (H+S), and high-altitude hypoxia exposure+celecoxib (H+Cel). Body weight and routine blood indicators were measured, and cardiac ultrasound examination were performed for heart rate (HR), pulmonary artery acceleration time to ejection time ratio (AT/ET), tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (S’), and left ventricular ejection fraction (LVEF) and fractional shortening (FS). Targeted metabolomic profiling was applied to detect the cardiac arachidonic acid (AA) metabolite levels. The contents of 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) in the heart, liver, brown adipose tissue, and plasma were quantified by ELISA. ② Eighteen mice were randomly assigned into plain+saline (P+S), high-altitude hypoxia exposure+saline (H+S) and high-altitude hypoxia exposure+12,13-diHOME (H+di) groups. Body weight, routine blood tests, and echocardiography were performed as above. ③ Thirty-two mice were randomly divided into high-altitude hypoxia exposure+saline (H+S), high-altitude hypoxia exposure+celecoxib (H+Cel), high-altitude hypoxia exposure+soluble epoxide hydrolase inhibitor (sEHI) (H+sEHI), and high-altitude hypoxia exposure+sEHI+celecoxib (H+sEHI+Cel) groups. Body weight, routine blood tests, and echocardiography were performed as above. Cardiac and plasma contents of 12,13-diHOME and epoxyeicosatrienoic acids (EETs) were measured by ELISA.

① Compared to the P+S group, the H+S group exhibited significantly reduction of cardiac 12,13-diHOME level (P<0.001), increased counts of white blood cells (WBC) and neutrophils (P<0.01) and decreased TAPSE, S’ and AT/ET both at resting state and under stress (P<0.01, P<0.001). Compared to the H+S group, the H+Cel group exhibited significantly increase of cardiac 12,13-diHOME level (P<0.05), reduced WBC and lymphocyte counts (P<0.01, P<0.05) and improved TAPSE and S' levels at resting state and under stress (P<0.01, P<0.001). ② Compared to the H+S group, the H+di group demonstrated significantly improvement of TAPSE at basal and under stress (P<0.001) and a trend towards improved TAPSE at resting state (P=0.0532), but no obvious differences was observed in WBC and neutrophil counts between the H+di group and the H+S group. ③ Compared to the H+Cel group, both the H+sEHI and H+sEHI+Cel groups exhibited significantly reduction of cardiac 12,13-diHOME level (P<0.01, P<0.05) though no statistical changes in cardiac function indicators. Compared to the H+S group, WBC counts and lymphocyte were decreased, and serum EETs level was incrased in the H+Cel group, H+sEHI group and H+sEHI+Cel group (P<0.01, P<0.001).

Celecoxib can elevate cardiac level of 12,13-diHOME and improves right heart function in mice after acute high-altitude hypoxia exposure through the CYP450-sEH metabolic pathway.

To investigate the characteristics of immune exhaustion in sepsis and analyze its association with gut microbiota translocation.

A total of 130 mice were randomly divided into a cecal ligation and puncture (CLP) group (n=100) and a Sham group (n=30) Mouse model of sepsis was established with CLP procedure. Flow cytometry was used to analyze the proportions of peripheral blood CD4⁺ T and CD8⁺T cells and programmed cell death protein 1 (PD-1) positive T cell subsets in mice. Bacterial colonization in organs such as the heart, liver and kidneys was quantified by plating homogenates of the organs. Pathological changes in immune organs were observed with HE staining. The expression and localization of CD4⁺, CD8⁺, and PD-1⁺cells in immune organs were detected with immunohistochemical staining, and Image J software was employed for subsequent quantification of the number of the positive cells.

HE staining demonstrated that immune organs exhibited varying degrees of pathological damages with disease progression. Compared with the Sham mice, the CLP mice exhibited significantly increased bacterial colonization in parenchymal organs and peripheral blood (P<0.05), notably in the liver, which showed the most severe infection. In the CLP group, the proportion of CD4⁺ T lymphocytes in peripheral blood at days 1, 3, and 5 postoperatively was decreased by 56%, 70.57%, and 87.42%, respectively, when compared with the Sham group (P<0.001). The proportion of CD8⁺ T lymphocytes was decreased by 48.33% relative to the Sham group only at day 5 (P<0.001). In contrast, the proportion of CD4⁺ T cell subsets expressing PD-1 was increased to 673.08, 423.08, and 600 times that of the Sham group, respectively, at the same postoperative time points (P<0.001). Immunohistochemical results showed that, in the CLP group, the proportion of CD4⁺ T cells in the thymus, spleen, and mesenteric lymph nodes was increased to 7.65, 2.66, and 3.7 times that of the Sham group, respectively, at the early-stage peak (P<0.001), and then these proportions were decreased by 82.8% (P<0.001), 41.9% (P<0.01), and 60.15% (P<0.001), respectively, at the late-stage trough when compared with the early-stage peak in the corresponding organs. The proportion of CD8⁺ positive cells was increased in the early stage and then decreased insignificantly, while the proportion of PD-1⁺ positive cells was increased continuously, and reached 6.24, 13.9, and 20.96 times that of the Sham group at the peak in the thymus, spleen, and mesenteric lymph nodes respectively (P<0.001), with their expression regions showing a rough overlap with those of CD4⁺ cells.

During sepsis, the inflammatory response can cause severe damage to immune organs and persistent exhaustion of CD4⁺T lymphocytes, leading to declined defenses against infection, which may be the main causes for exacerbated gut microbiota translocation and then systemic infection.

To investigate the role of poly(rC)-binding protein 1 (PCBP1) in cadmium (Cd)-induced ferroptosis in mouse neuroblastoma Neuro-2a (N2A) cells.

N2A cells were exposed to a concentration gradient of CdCl₂ (0, 1, 2, 4 μmol/L) for 72 h. Cell viability was assessed by trypan blue staining. Western blotting was employed to detect the expression of ferroptosis-related proteins (GPX4, HMOX1, ACSL4) and PCBP1. Intracellular Fe²⁺ level and lipid peroxidation were detected using FerroOrange and BODIPY^581/591 C11 probes, respectively. Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, was applied to confirm the critical role of ferroptosis in Cd-induced cytotoxicity. Molecular docking was performed to elucidate the interaction between PCBP1 and ferritin, as well as the binding sites of Cd²⁺. PCBP1 overexpression plasmid was further constructed for functional validation.

Cd exposure suppressed cell viability in N2A cells in a dose-dependent manner (P<0.01), significantly down-regulated GPX4 expression (P<0.05), up-regulated HMOX1 expression (P<0.01), and induced Fe²⁺ overload and lipid peroxidation (P<0.01). Molecular docking revealed that Cd²⁺ directly bound to the KH2 domain of PCBP1 and then co-localized on the outer surface of ferritin heavy chain. Overexpression of PCBP1 markedly reversed Cd-induced Fe²⁺ accumulation, GPX4 down-regulation, lipid peroxidation, and cell death.

Cd exposure disrupts PCBP1-mediated iron homeostasis via transcriptional suppression and competitive displacement of metal ions, and then synergistically drives Fe²⁺ overload-triggered ferroptosis cascades, ultimately leading to neurotoxicity. Targeting PCBP1-mediated iron homeostasis can effectively mitigate Cd-induced neurotoxicity, and may serve as a novel therapeutic strategy.

To explore the differences in therapeutic efficacy and possible mechanism of different routes of administration of fullerene nanoparticles in the treatment of radiation retinopathy.

Eight-week-old adult male SD rats were randomly divided into blank group (Control), irradiation group (X-Ray), irradiation＋vitreous cavity administration group [X+F(IVT)], irradiation＋ocular surface administration group [X+F(OS)], and irradiation＋intravenous administration group [X+F (IV)], with 5 rats in each group. The blank group was not treated, the irradiation groups exposed to X-ray irradiation to establish the model, and fullerenol nanoparticles were given to the treatment groups through different routes after irradiation. At 7, 14, and 28 d after modeling, body weight and fundus changes were measured to evaluate drug safety, retinal optical coherence tomography (OCT) was used to observe the change in retinal tissue structure, and electroretinography (ERG) was applied for oscillatory potentials (OPs) to evaluate visual function. CD31 immunofluorescence staining was carried out to evaluate retinal endothelial vascular status, and in vivo imaging was utilized to evaluate the accumulation of fullerenol nanoparticles in the eyes.

The growth curves of body weight demonstrated that fullerenol nanoparticles did not affect the growth and development of rats, with no statistical difference between the treatment groups and the control group. Irradiation resulted in a significant reduction in visual function, decreased amplitudes of a-wave and b-wave, and declined OPs (P<0.01), and significantly increased thicknesses of the ganglion cell layer (GCL) and the inner nuclear layer (INL) in the retinas, as evidenced by OCT (P<0.01), along with a notably absent presence of CD31-positive cells (P<0.01). Notably, the X+F(IVT) group obtained significantly improved visual function after intravitreal administration, effectively maintained thickness of the GCL and INL, and prevention against the loss of CD31-positive cells (P<0.01). However, no such effective results were observed in the irradiated groups receiving intravenous either ocular surface administration. In vivo imaging revealed that intravitreal administration maintained high ocular accumulation of fullerene for 96 h, while ocular surface administration sustained these concentrations for only 12 h. Intravenous administration, in contrast, only led to a predominant drug distribution in vascular-rich areas, but reduced ocular accumulation.

Fullerene nanoparticles possess a therapeutic effect on radiation retinopathy, and the intravitreal administration route demonstrates better efficacy than ocular surface and intravenous administration.

To investigate the role and mechanism of ginsenoside Rk3 in alleviating the senescence of retinal pigment epithelial (RPE) cells and in treating neovascular age-related macular degeneration (nAMD).

An ARPE-19 cell senescence model induced by hydrogen peroxide and an nAMD mouse model were subjected to validate the pharmacological activity of ginsenoside Rk3 in reducing RPE cell senescence and shrinking choroidal neovascularization (CNV) area. Transcriptome sequencing was performed to analyze the changes in differential gene expression profiles. Western blotting was used to detect the expression levels of mTOR, S6K1, p-S6K1, 4EBP1, p-4EBP1, p62, and LC3A/B. Molecular docking and dynamics simulations were conducted to analyze the binding affinity of ginsenoside Rk3 with mTOR protein.

① Cell experiments showed that ginsenoside Rk3 significantly alleviated the senescence in ARPE-19 cells (P<0.05). ② Animal experiments confirmed that ginsenoside Rk3 significantly reduced the retinal CNV area in nAMD mice (P<0.01), and its efficacy was comparable to the first-line clinical drug aflibercept (P>0.05). ③ Transcriptome sequencing suggested that ginsenoside Rk3 led to enrichment of the PI3K-Akt signaling pathway. Western blotting showed that ginsenoside Rk3 inhibited the overactivation of mTORC1 signaling (P<0.05) and simultaneously enhanced cellular autophagy (P<0.05). ④ Molecular docking and dynamics simulations further validated that ginsenoside Rk3 probably targets mTOR to alleviate RPE cell senescence.

Ginsenoside Rk3 alleviates RPE cell senescence and reduces retinal CNV area in nAMD mice by enhancing autophagy through inhibition of mTOR.

To investigate the role and underlying mechanism of activating transcription factor 3 (ATF3) in suppressing lipopolysaccharide (LPS)-induced autophagy and inflammatory responses in macrophages.

Firstly, the gene expression omnibus (GEO) database was used to analyze ATF3 expression in peripheral blood mononuclear cells (PBMCs) from sepsis patients, and gene set enrichment analysis (GSEA) was performed to identify enriched signaling pathways. Secondly, RAW264.7 macrophages were divided into a blank control group and an LPS-stimulated group (100 ng/mL LPS). Western blotting and immunofluorescence assay were used to detect ATF3 protein expression and observe its subcellular localization, respectively. Lentiviral transduction was used to generate ATF3 knockdown and overexpression cell lines to evaluate their effects on cytokine release and bacterial clearance. Cleavage Under Targets and Tagmentation (CUT&Tag) sequencing was employed to identify downstream target genes transcriptionally regulated by ATF3. Furthermore, the impact of ATF3 knockdown or overexpression on autophagy-related gene 5 (ATG5), autophagy-related gene 16-like 1 (ATG16L1), and autophagy levels was evaluated.

GEO analysis revealed that ATF3 expression was significantly elevated in PBMCs from sepsis patients (P<0.01), and GSEA showed significant enrichment of autophagy-related and inflammation-related pathways (P<0.01). In RAW264.7 cells, 100 ng/mL LPS stimulation significantly increased ATF3 expression in the nucleus than the blank control group (P<0.01). ATF3 knockdown led to increased secretions of TNF-α and IL-6 and enhanced bacterial clearance of macrophages (P<0.01), whereas ATF3 overexpression significantly suppressed TNF-α and IL-6 releases, and remained bacterial clearance at a low level when compared with the conditions in the negative control (NC) group (P<0.01). CUT&Tag results demonstrated that ATF3 was enriched at the promoter regions of key autophagy genes Atg5 and Atg16l1. Compared with the NC group, ATF3 knockdown significantly up-regulated the protein levels of LC3-II/I, ATG5, and ATG16L1 while decreased p62 expression (P<0.01). Conversely, ATF3 overexpression inhibited the expression of LC3-II/I, ATG5, and ATG16L1 (P<0.01), but had no significant effect on p62 level.

Sepsis induces elevated ATF3 expression in macrophages, and suppresses autophagic activity and down-regulates pro-inflammatory cytokines TNF-α and IL-6, which probably mediated by ATF3 regulating transcription of ATG5 and ATG16L1, suggesting ATF3 as a potential therapeutic target for autophagy-inflammation imbalance.

To investigate the inhibitory effect of erianin on T cell proliferation and its underlying mechanism.

Peripheral blood mononuclear cells (PBMCs) were isolated using density gradient centrifugation, and T cells were purified by magnetic-activated cell sorting (MACS) with immunomagnetic beads, followed by being activated with anti-human CD3 antibodies and anti-human CD28 antibodies. The activated T cells were labeled with carboxyfluorescein succinimidyl ester (CFSE), and the effects of erianin (0.05~0.20 μmol/L) on the proliferation, apoptosis, expression of activation marker cluster of differentiation 25 (CD25), cell cycle distribution of activated T cells, as well as the survival rate of resting T cells were assessed using flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was applied to determine the secretion levels of IL-2 and IL-17 in the culture supernatant of erianin-treated activated T cells. Western blotting was employed to examine the impact of erianin on the protein expression of cell division cycle protein 2 (CDC2), phosphorylated CDC2 (p-CDC2), and Cyclin B1. The differences were observed between the erianin-treated group and the positive control group (activation with CD3/CD28 antibodies).

CFSE proliferation assay demonstrated that the proliferative rate of activated T cells was in a concentration-dependent decline after 0.05~0.20 μmol/L erianin treatment (P<0.0001), with a half-maximal inhibitory concentration (IC₅₀) of 0.09±0.10 μmol/L. No significant differences were observed in apoptotic rates or survival rates among the erianin-treated groups (activated and resting T cells) and the positive control cells. Analysis of T cell activation markers revealed that erianin had no impact on CD25 expression or IL-2 secretion. However, ELISA results indicated erianin exerted a significant suppression on the secretion of pro-inflammatory cytokine IL-17 (P<0.0001). Cell cycle analysis showed that erianin arrested activated T cells at the G2/M phase (P<0.05). Further mechanistic investigations demonstrated that while erianin did not alter CDC2 phosphorylation or total CDC2 expression, but it markedly down-regulated CyclinB1 expression (P<0.01).

Erianin exhibits potent immunomodulatory activity by suppressing activated T cell proliferation through down-regulating Cyclin B1.

To explore the impact of Shexiang Baoxin Pill (SXBXP, a traditional Chinese patent medicine, broadly applied for the treatment of cardiovascular diseases) on coronary microvascular disease (CMD) and investigate the role and underlying mechanisms of muscone, a key bioactive component of the pills, in the treatment.

A total of 16 ob/ob mice (8 weeks old) were randomly and equally divided into an ob/ob-SXBXP group and a ob/ob-Control group, receiving 10 mg/kg·d SXBXP or PBS via oral gavage, and another 8 wild-type mice with the same genetic background (WT group) were subjected as a negative control group. Cell model of CMD was established based on mouse coronary microvascular endothelial cells (MCMEC) under ischemia and hypoxic (HI) condition, and the cells were further treated with 20 μg/mL SXBXP (HI+SX) and 30 μmol/L muscone (HI+Muscone), respectively. Echocardiography was carried out for coronary flow reserve (CFR) and left ventricular function, and laser speckle imaging was applied to evaluate myocardial blood flow (MBF). Microvascular density in the heart was evaluated with CD31 immunofluorescence staining. The expression levels of vascular endothelial growth factor (VEGF) in cardiac microvascular endothelial cells of both mouse and cell models were detected by immunofluorescence staining and Western blot analysis. The proliferation and angiogenesis of MCMEC were observed by 5-ethynyl-2'-deoxyuridine staining and angiogenesis experiments.

In the ob/ob-Control group of mice, the levels of CFR, MBF, and cardiac microvascular density were significantly lower than those in the WT group (P<0.05), and these indicators were significantly improved in the ob/ob-SXBXP group when compared with the ob/ob-Control group (P<0.05), which indicates that SXBXP improves the CMD phenotype. The expression level of VEGF in cardiac microvascular endothelial cells was significantly lower in the ob/ob-Control mice than the WT mice (P<0.05), while the level in the ob/ob-SXBXP group was significantly higher than that in the ob/ob-Control group (P<0.05), illustrating that SXBXP may ameliorate CMD through VEGF-mediated microvascular angiogenesis. In vitro experiments further revealed that the VEGF expression level and the proliferation and angiogenesis abilities in MCMEC were significantly lower in the HI group than the cells under the normoxia control condition (P<0.05). Both SXBXP and muscone treatment resulted in enhanced expression of VEGF and improved proliferative and angiogenesis abilities of MCMEC (P<0.05). These results suggest that muscone could improve CMD by VEGF-mediated microvascular angiogenesis.

SXBXP can improve CMD. Muscone, as a key component of SXBXP, promotes microvascular angiogenesis by inducing the expression of VEGF, then enhances myocardial perfusion, and consequently alleviates CMD.

To investigate the effect of ultra-low dose of dimethyl sulfoxide (DMSO) on the proliferation of skin fibroblasts and to explore its underlying molecular mechanism.

MTT assay was used to determine the effect of different concentrations of DMSO on the proliferation of skin fibroblasts. Pull-down assay with 7-methylguanosine triphosphate (⁷mGTP) and Western blotting was employed to detect the changes in eukaryotic initiation factor 4E (eIF4E) and its binding protein, 4E-BP1, and eukaryotic translation initiation factor 4G (eIF4G). After intervention with mTOR inhibitor, rapamycin, the alterations in the expression and phosphorylation levels of proteins within the PI3K/Akt/mTOR signaling pathway were examined with Western blotting.

Treatment with 11.0 nmol/L DMSO significantly increased both the cell proliferation rate (P<0.05) and the activity of the cap-dependent translation initiation luciferase reporter gene (P<0.05). Results from 7mGTP pull-down assay and Western blotting demonstrated that 11.0 nmol/L DMSO notably inhibited the binding of 4E-BP1 to eIF4E (P<0.05) while promoting the binding of eIF4G to eIF4E (P<0.05). Compared with the control group, the phosphorylation levels of p-Akt (S473), p-mTOR (S2448), p-4E-BP1 (T37/46), and p-p70S6K (T421/424) were upregulated (P<0.05); the total protein expressions of Akt, mTOR, p70S6K, S6, eIF4E, and 4E-BP1 were increased to varying degrees(P<0.05). In the RAPA intervention group, the phosphorylation levels of p-Akt (S473), p-mTOR (S2448), p-p70S6K (T421/424), and p-S6 (S235/236) were significantly lower than those in the control group (P<0.05). When comparing the RA + DMSO group with the RA group, the phosphorylation levels of all aforementioned proteins were significantly upregulated except for p-eIF4E (S209) (P<0.05). For protein expression analysis: relative to the control group, the DMSO group exhibited increased expressions of Akt, p70S6K, and mTOR (P<0.05) except for 4E-BP1; the RAPA group showed significant downregulation in all these proteins (P<0.05); compared with the RA group, the RA + DMSO group displayed significantly higher expressions of all these proteins except for p70S6K (P<0.05).

Ultra-low dose of DMSO (11.0 nmol/L) promotes the proliferation of mouse skin fibroblasts by mediating the PI3K/Akt/mTOR signaling pathway, thereby potentially accelerating wound healing.

To analyze the diagnostic process and clinical characteristics of autoimmune gastritis(AIG) in order to improve the awareness and diagnostic proficiency of this disease.

A retrospective cohort study was conducted on 114 patients diagnosed with AIG in Army Medical Center of PLA between January 2021 and June 2024. Comprehensive statistical analysis was performed on clinical data, including demographic characteristics(age, sex), clinical symptoms, comorbidities, diagnostic process, Helicobacter pylori(H. pylori) infection and treatment history, laboratory indicators [results of routine blood test, anemia-related indices, thyroid function, anti-parietal cell antibody(APCA), intrinsic factor antibody(IFA)], and gastrointestinal endoscopic findings(frequency and endoscopic features).

Among the 114 patients, males accounted for 28.1%(32/114) and females for 71.9%(82/114), and they were at a mean age of 56.3±8.4 years. Predominant symptoms included epigastric/upper abdominal pain(47.4%, 54/114) and postprandial fullness(43.0%, 49/114), while 24.6%(28/114) reported acid reflux or heartburn. Diagnostic delay occurred in 76.4%(87/114) of patients, with a median delay duration of 11.5 months. Primary diagnostic clues were endoscopic reverse gradient atrophy(significantly more severe mucosal atrophy in the gastric corpus/fundus versus antrum; 53.5%, 61/114) and repeated H. pylori eradication failure(≥2 attempts; 22.8%, 26/114). Positivity rate of thyroid peroxidase antibody(TPOAb) and thyroglobulin antibody(TgAb) was 56.9%(33/58) and 36.2%(21/58), respectively. APCA positive rate was 98.8%(81/82), IFA positive rate was 34.1%(28/82), and dual-antibody rate was 32.9%(27/82). Anemia was present in 25.7%(26/101) of the patients. Gastric neuroendocrine tumors(NET) were found in 12.2%(14/114), intraepithelial neoplasia in 5.3%(6/114), and gastric adenocarcinoma in 0.9%(1/114). Among colonoscopy-examined patients, tubular adenomas occurred in 25.0%(13/52) and colorectal malignancies in 3.4%(2/58). There were 18.4%(21/114) patients having gallbladder-related diseases, 7.9%(9/114) having diabetes mellitus, and 1.8%(2/114) of subacute combined degeneration of the spinal cord.

AIG is frequently associated with diagnostic delay. The reverse pattern of atrophy on endoscopy serves as a critical diagnostic clue, necessitating enhanced recognition in endoscopists. Patients with recurrent H. pylori eradication failure (≥2 attempts) should be evaluated for AIG.

To investigate the influencing factors for low anterior resection syndrome (LARS) at one year after ileostomy reversal in patients who have undergone radical resection for rectal cancer, and to inform clinical interventions.

A retrospective cohort study was conducted on 312 patients who successfully underwent ileostomy reversal after radical resection for rectal cancer between January 2023 and January 2024 at 3 tertiary hospitals in Chongqing. Based on LARS scores at 1-year after stoma reversal, they were divided into a LARS group (score ≥21) and a non-LARS group (score≤20). Clinical data were collected from the medical record system, including age, body mass index (BMI), sex, tumor size, tumor distance from the anal verge, T stage, N stage, date of low anterior resection, neoadjuvant therapy, postoperative chemotherapy, anastomotic leakage, and date of ileostomy reversal. Univariate analysis was used to screen potential influencing factors, and variables with P<0.2 were included in a multivariate logistic regression model. Binary stepwise regression analysis was applied to further analyze significant influencing factors for LARS at 1 year after ileostomy reversal.

In the cohort, there were 127 patients assigned into the LARS group and 185 into the non-LARS group. The incidence of LARS at 1 year after ileostomy reversal was 40.70%, with mild cases accounting for 21.79% and severe ones for 18.91%, and a mean LARS score of 14.52±11.64. Multivariate logistic regression analysis showed that neoadjuvant therapy (yes vs no: OR=1.830, 95%CI: 1.088~3.089; P=0.023), tumor distance from anal verge ≤5 cm (vs >5 cm: OR=2.044, 95%CI:1.249~3.374; P=0.005), occurrence of anastomotic leakage (yes vs no: OR=7.470, 95%CI: 2.247~34.102; P=0.003), time to reversal (≥181 d vs 91~180 d: OR=2.297, 95%CI:1.363~3.917; P=0.002), and N stage (N1~N2 vs N0: OR=1.650, 95%CI: 1.009~2.717; P=0.047) were significant influencing factors for LARS at 1 year after ileostomy reversal.

Our results suggest that anastomotic leakage, time to reversal ≥181 d, tumor distance from anal verge ≤5 cm, neoadjuvant therapy, and N stage N1~N2 are associated with the occurrence of LARS at 1 year after ileostomy reversal in patients following radical resection of rectal cancer. Clinical healthcare providers should implement early intervention and long-term follow-up for patients with high-risk factors both before and after stoma reversal.

To analyze the dynamic change in placental growth factor (PLGF) level in patients with preeclampsia (PE) and its role in predicting pregnancy outcomes.

A retrospective cohort study was conducted on 198 PE patients admitted to Department of Obstetrics of Tianjin Beichen Hospital from January 2021 to January 2024. Among them, 151 cases were identified as non-severe PE and 47 cases as severe PE. During the same period, another 100 healthy pregnant women were included in the department and served as the control group. According to the final pregnancy status of the PE patients, they were divided into an adverse outcome group (88 cases) and a good outcome group (110 cases). Locally Weighted Scatterplot Smoothing (LOWESS) was used to analyze the relationship between vascular endothelial function indicators and PLGF level. Logistic regression was employed to identify the influencing factors for adverse pregnancy outcomes. Receiver operating characteristic (ROC) curve was plotted to evaluate the value of PLGF level for predicting adverse pregnancy outcomes in patients with non-severe PE and severe PE.

The PLGF level was in a peak shape at different gestational weeks, relatively low at 28~29 ⁺⁶ weeks of gestation, gradually increasing with the increment of gestational weeks, reaching a peak at 30~31 ⁺⁶ weeks of gestation, and then gradually decreased (P<0.05). The PLGF level was gradually reduced in the control group, non-severe PE group, and severe PE group in turn (P<0.05). LOWESS analysis showed that the PLGF level exhibited certain nonlinear relationship with soluble fms-like tyrosine kinase receptor 1 (sFlt-1), vascular endothelial growth factor (VEGF), nitric oxide (NO), thrombomodulin (TM), thromboxane A2 (TXA2), and Von Willebrand factor (VwF). The results of logistic regression analysis indicated that after gradually eliminating collinearity confounding factors and adjusting for each covariate, there was still an independent correlation between the PLGF level at 28~29 ⁺⁶ gestational weeks and pregnancy outcome (OR=0.593, 95%CI: 0.583~0.778, P<0.001). After converting the PLGF level into a binary variable, there was an independent correlation between high PLGF level and pregnancy outcome (OR=0.773, 95%CI: 0.671~0.885, P<0.001). Compared with the quintile with the lowest PLGF (Q1), as the PLGF level gradually increased (Q2 to Q5), the correlation effect values were (OR=0.765, 95%CI: 0.639~0.837, P=0.092), (OR=0.752, 95%CI: 0.624~0.818, P=0.056), (OR=0.696, 95%CI: 0.615~0.813, P=0.027), and (OR=0.642, 95%CI: 0.591~0.733, P<0.001), and the trend test was statistically significant (P_trend<0.001). ROC curve analysis revealed that the area under the ROC curve (AUC) of serum PLGF level at 28-29⁺⁶ gestational weeks in predicting adverse pregnancy outcomes in non-severe PE patients was 0.830 (95%CI: 0.635~0.917), the optimal critical threshold was 75.47 ng/L, the sensitivity was 88.37%, the specificity was 71.30%, the positive predictive value was 55.07%, and the negative predictive value was 93.90%. Its AUC value of the level for the prediction in patients with severe PE was 0.874 (95%CI: 0.677~0.923), the optimal critical threshold was 38.53 ng/L, the sensitivity was 88.89%, the specificity was 50.00%, the positive predictive value was 97.56%, and the negative predictive value was 16.67%.

At 28~29⁺⁶ gestational weeks, PLGF has an independent correlation with pregnancy outcomes and shows a good predictive performance for adverse pregnancy outcomes in patients with non-severe PE and severe PE.

To analyze the characteristics of real-world adverse drug events (ADEs) of trabectedin based on the FDA Adverse Event Reporting System (FAERS) database in order to provide references for clinical drug safety management.

A total of 1 349 trabectedin-related reports were extracted from the FAERS database from Q1 2007 to Q4 2024. Using the MedDRA coding classification system for system organ class (SOC) and preferred term (PT), signal detection was performed through 4 proportional imbalance methods, including reporting odds ratio (ROR) and proportional reporting ratio (PRR). Subgroup analyses by gender, age, and temporal trends were also conducted.

Hematological and lymphatic system disorders and hepatobiliary system disorders were the primary SOCs involved. High-frequency PTs included neutropenia (123 cases) and anemia (117 cases). Eight potential ADEs that have not been listed in the drug product instruction were identified. The median onset time of ADEs was 21 d, showing an early failure pattern, with differences observed by gender (females more prone to hematological toxicity) and age (elderly more susceptible to febrile neutropenia).

Trabectedin requires close attention to hematological toxicity, hepatotoxicity, and newly identified multi-system potential risks. Clinically, monitoring should be strengthened based on time windows and population characteristics to optimize drug regimens. Countermeasure　It is recommended to strengthen the full cycle monitoring of anti-tumor drugs, standardize the reporting of adverse reactions, and establish a multi-departmental collaborative research platform.

To investigate the potential causal associations between 3 common subjective sleep problems, daytime sleepiness, insomnia, and sleep apnea, and epigenetic age acceleration.

A two-sample Mendelian randomization (MR) study was conducted the publicly available genome-wide association study (GWAS) data to assess the causal effects of self-reported sleep problems on 4 indicators of epigenetic age acceleration, including intrinsic epigenetic age acceleration (IEAA), GrimAge acceleration, HannumAge acceleration, and PhenoAge acceleration. The primary analytical method was inverse-variance weighting (IVW), supplemented by sensitivity analyses using MR-Egger regression and the weighted median (WM) method to examine the robustness of the findings.

IVW showed that daytime sleepiness was significantly positively associated with IEAA (β=1.83, 95%CI: 0.17~2.49, P=0.031) and HannumAge acceleration (β=1.81, 95%CI: 0.21~2.42, P=0.027), suggesting a potential accelerating effect on epigenetic aging. Insomnia also showed significant positive associations with IEAA (β=1.57, 95%CI: 0.40~2.73, P=0.009) and GrimAge acceleration (β=1.37, 95%CI: 0.18~2.56, P=0.024). No significant causal relationship was observed between sleep apnea and any indicator of epigenetic age acceleration (P>0.05).

Daytime sleepiness and insomnia may accelerate epigenetic aging, indicating their potential biological role in the aging process. The impact of sleep apnea remains unclear and warrants further investigation.