Background Studies have shown that benzo(a)pyrene (BaP) exhibits neurotoxicity and can induce cognitive dysfunction. Olfactory dysfunction is an early marker of mild cognitive impairment; however, the mechanism by which BaP exposure causes this impairment is still unclear. Objective To investigate the effects of BaP exposure on olfactory function in mice. Methods Thirty 5-month-old male C57BL/6 mice were randomly assigned to five groups (n=6 per group): blank control, solvent control (olive oil), and low, medium and high doses (0.72, 1.44, and 2.89 mg·kg⁻¹, respectively). Following one week of acclimatization, BaP was administered intranasally every other day. Behavioral changes were assessed using the buried food test and Morris water maze (MWM). Olfactory bulb tissues were subsequently harvested for analysis. Hematoxylin-eosin (HE) staining was used to evaluate pathological changes, while immunofluorescence and quantitative polymerase chain reaction (qPCR) were employed to examine the expression and distribution of protein and mRNA expressions and distributions of olfactory marker protein (OMP), membrane-spanning 4-pass A1 (MS4A1), trace amine-associated receptor1 (TAAR1). Results The buried food test revealed that BaP exposure significantly prolonged the time taken to find food in a dose-dependent manner (F=56.753, P< 0.01). MWM results showed significant main effects for both time (F=128.5, P<0.01) and dose (F=3.889, P<0.05), with a significant interaction effect between them (F=2.128, P<0.05). HE staining showed that in the 2.89 mg·kg⁻¹ group, although granule remained abundant, mitral cell layer neurons exhibited structural atrophy and deep staining. Immunofluorescence demonstrated a decreased distribution of OMP, MS4A1, and TAAR1 in the olfactory nerve layer and glomerular layers in the 2.89 mg·kg⁻¹ group compared with the blank control group (F=11.590, P<0.01; F=12.807, P<0.01; F=7.436, P<0.01). Furthermore, mRNA expression levels of OMP, MS4A1, and TAAR1 in the 2.89 mg·kg⁻¹ group were also significantly downregulated compared to the control group (F=6.720, P<0.01; F=16.931, P<0.01; F=48.060, P<0.01). Conclusion BaP exposure leads to olfactory dysfunction in mice by inducing pathological damage to mitral cells and reducing the expression of key olfactory receptors and markers in the olfactory bulb.

Background Studies have shown that benzo(a)pyrene (BaP) exhibits neurotoxicity and can induce cognitive dysfunction. Olfactory dysfunction is an early marker of mild cognitive impairment; however, the mechanism by which BaP exposure causes this impairment is still unclear. Objective To investigate the effects of BaP exposure on olfactory function in mice. Methods Thirty 5-month-old male C57BL/6 mice were randomly assigned to five groups (n=6 per group): blank control, solvent control (olive oil), and low, medium and high doses (0.72, 1.44, and 2.89 mg·kg⁻¹, respectively). Following one week of acclimatization, BaP was administered intranasally every other day. Behavioral changes were assessed using the buried food test and Morris water maze (MWM). Olfactory bulb tissues were subsequently harvested for analysis. Hematoxylin-eosin (HE) staining was used to evaluate pathological changes, while immunofluorescence and quantitative polymerase chain reaction (qPCR) were employed to examine the expression and distribution of protein and mRNA expressions and distributions of olfactory marker protein (OMP), membrane-spanning 4-pass A1 (MS4A1), trace amine-associated receptor1 (TAAR1). Results The buried food test revealed that BaP exposure significantly prolonged the time taken to find food in a dose-dependent manner (F=56.753, P< 0.01). MWM results showed significant main effects for both time (F=128.5, P<0.01) and dose (F=3.889, P<0.05), with a significant interaction effect between them (F=2.128, P<0.05). HE staining showed that in the 2.89 mg·kg⁻¹ group, although granule remained abundant, mitral cell layer neurons exhibited structural atrophy and deep staining. Immunofluorescence demonstrated a decreased distribution of OMP, MS4A1, and TAAR1 in the olfactory nerve layer and glomerular layers in the 2.89 mg·kg⁻¹ group compared with the blank control group (F=11.590, P<0.01; F=12.807, P<0.01; F=7.436, P<0.01). Furthermore, mRNA expression levels of OMP, MS4A1, and TAAR1 in the 2.89 mg·kg⁻¹ group were also significantly downregulated compared to the control group (F=6.720, P<0.01; F=16.931, P<0.01; F=48.060, P<0.01). Conclusion BaP exposure leads to olfactory dysfunction in mice by inducing pathological damage to mitral cells and reducing the expression of key olfactory receptors and markers in the olfactory bulb.

Objectives: . The prognostic value of the pretreatment albumin-to-alkaline phosphatase ratio (AAPR) in head and neck cancer (HNC) remains uncertain. This meta-analysis aimed to evaluate the predictive role of AAPR for survival outcomes in patients with HNC. Methods: . A comprehensive search of the Cochrane Library, PubMed, and Embase databases was conducted to identify relevant studies published up to July 30, 2024. We included studies on AAPR and survival outcomes in HNC patients. Results: . Eight studies comprising 1,737 HNC patients were analyzed using random-effects models. Lower AAPR values were significantly correlated with worse overall survival (hazard ratio [HR], 2.08), progression-free survival (HR, 2.00), and disease-free survival (HR, 2.18). Sensitivity analyses confirmed the robustness of these results, with no significant publication bias detected. Conclusion . Our findings suggest that pretreatment AAPR could serve as a valuable and cost-effective prognostic indicator in HNC, potentially aiding clinicians in risk stratification and treatment decision-making. However, additional validation studies are warranted to confirm its clinical applicability.

Objective To investigate the probability and dosimetric risk factors of lung injury after sequential immune checkpoint inhibitors (ICIs) and thoracic radiotherapy. Methods A retrospective analysis was conducted on 139 patients who received sequential ICIs and thoracic radiotherapy in Xuzhou Cancer Hospital and Affiliated Hospital of Xuzhou Medical University between February 2020 and February 2024. The relationships of clinical factors and lung and heart volume dose parameters with grade ≥ 2 acute lung injury (ALI) in patients with thoracic tumors were studied using univariable (χ² test, t test, nonparametric test) and multivariable (binary logistic regression analysis) methods. The thresholds of dosimetric risk factors were determined using the receiver operating characteristic curves. Clinical factors included age, gender, smoking history, type of ICIs, cycle of ICI application, and the interval between ICI application and thoracic radiotherapy. Dose parameters included total radiotherapy dose, single dose, planning target volume, maximum dose of planning target volume, average dose of planning target volume, total lung volume, heart volume, and the V₅, V₁₀, V₁₅, V₂₀, V₂₅, V₃₀, V₃₅, and V₄₀ of lung and heart. Results The incidence of grade ≥ 2 ALI in the included cases was 36% (50/139). The χ² test did not find any statistically significant clinical factors. In the univariable and binary Logistic regression analysis, lung V₁₅ and V₂₀, heart V₁₅ and V₂₀, and lung volume were independent risk factors for the occurrence of grade ≥ 2 ALI in sequential ICIs and thoracic radiotherapy. The thresholds were 18.51% for lung V₁₅, 14.43% for lung V₂₀, 32.41% for heart V₁₅, and 17.74% for heart V₂₀. Conclusion For patients who are going to receive thoracic radiotherapy after ICIs, the thresholds of lung V₁₅ and V₂₀ and heart V₁₅ and V₂₀ in the radiotherapy plan are recommended to be less than 18.51%, 14.43%, 32.41%, and 17.74%, respectively, which can effectively reduce the occurrence of grade ≥ 2 ALI.

This paper reported a type 1 diabetes patient who had severe diabetic nephropathy, retinopathy, hypertension, and hypothyroidism before pregnancy. The patient's blood glucose control was poor before pregnancy, and the complications were not properly treated. This was an unintended pregnancy, with a pre-pregnancy glycated hemoglobin A1c of 7.8% and early pregnancy urine protein of 3.81-4.53 g/24 h. Considering the patient's poor blood glucose control before pregnancy and the lack of proper treatment for multiple complications including nephropathy, a multidisciplinary consultation at an external hospital recommended termination of the pregnancy. However, the patient was determined to continue the pregnancy and was referred to Peking University First Hospital. Through strict blood glucose control, monitoring and evaluation of complications, and comprehensive management, the patient's blood glucose and blood pressure were well controlled during pregnancy. Regular monitoring of urine protein, renal function, and ocular fundus was conducted. At 31 weeks and 4 days of gestation, the patient's 24-hour urine protein significantly increased. After promoting fetal lung maturity, a cesarean section was performed at 34 weeks and 1 day of gestation, resulting in a successful delivery with good maternal and neonatal outcomes. At the 42-day postpartum follow-up, the patient's blood glucose and blood pressure were stable, urine protein returned to pre-pregnancy levels, and the infant was in good general condition.

Objective:As medical demands rose rapidly and innovative pharmaceuticals continuously launched onto the market,the National Essential Medicines List(NEML)confronted a novel challenge whether or not to include new medicines.The practice of WHO including new medicines in the WHO Essential Medicines List(WHO EML)was analyzed to provide references for the adjustment of NEML.Methods:Based on the theory of the right to life and health,it explored the theoretical basis of WHO incorporating new medicines into WHO EML.The cancer medicines were taken as the examples to investigate evaluation criteria.Results:For the selection of new medicines,WHO refined multi-dimensional evaluation criteria and took targeted measures to improve selection process and management system.Conclusion:When China attempted to include new drugs in the NEML,it was necessary to adjust selection concept,optimize selection process,improve NEML structure and content,improve selection criteria and strengthen the construction of selection and management guarantee system.

Objective:To investigate the influencing factors and perinatal outcomes associated with monozygotic twins (MZT) following elective single embryo transfer (eSET) via in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET). Methods:A retrospective cohort study was conducted on 12 079 patients who achieved pregnancy after undergoing IVF/ICSI-eSET at Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University between January 2015 and September 2023. Patients were stratified into two groups based on ultrasound findings 30 d post-transfer: singleton pregnancy group and MZT pregnancy group. Finally, 300 MZT and 1 500 single pregnancies, which were randomly matched according to 1∶5 were included by study period. General patients' characteristics, embryo-related factors, and perinatal outcomes were compared between the two groups. A multivariate logistic regression model was employed to identify risk factors for MZT after single embryo transfer, adjusting for potential confounding variables.Results:The incidence of twin pregnancy following single embryo transfer was 2.48% (300/12 079), which was higher than that of naturally conceived monozygotic twin pregnancy. No significant difference was found in baseline characteristics between the two groups (all P>0.05). The blastocyst transfer rate was higher in the MZT pregnancy group [93.3% (280/300)] than in the singleton pregnancy group [88.8% (1 332/1 500), P=0.022]. Multivariate logistic regression analysis also showed that blastocyst transfer was associated with an increased risk of MZT ( OR=0.552, P=0.016, 95% CI: 0.341-0.894). Analysis of blastocyst cycles showed that the risk of MZT was higher when transferring high-quality blastocysts [79.6% (223/280) vs. 67.8% (903/1 332), P<0.001], where as a trophectoderm (TE) grading of C [20.4% (57/280) vs. 32.2% (429/1 332), P<0.001] had a lower risk of MZT. After adjusting for confounding factors, the risk of MZT was found to increase with the transfer of blastocysts with a B-grade inner cell mass (ICM) ( OR=0.601, P=0.001, 95% CI: 0.442-0.819) and A/B grade TE (grade A: OR=2.951, P<0.001, 95% CI: 1.980-4.399; grade B: OR=1.840, P<0.001, 95% CI: 1.315-2.576). The risk of complications during pregnancy [47.7% (143/300) vs. 19.3% (289/1 500), P<0.001], preterm labor [55.1% (140/254) vs. 7.4% (101/1 368), P<0.001], and the risk of stillbirth [3.7% (11/300) vs. 1.5% (22/1 500), P=0.016] were significantly higher in the MZT pregnancy group than in the singleton pregnancy group. Conclusion:Assisted reproductive technology may contribute to the risk of MZT. Transfer of blastocysts, particularly those with loose ICM arrangement and dense TE arrangement, appears to increase the risk of MZT in patients undergoing eSET.

This paper reported a type 1 diabetes patient who had severe diabetic nephropathy, retinopathy, hypertension, and hypothyroidism before pregnancy. The patient's blood glucose control was poor before pregnancy, and the complications were not properly treated. This was an unintended pregnancy, with a pre-pregnancy glycated hemoglobin A1c of 7.8% and early pregnancy urine protein of 3.81-4.53 g/24 h. Considering the patient's poor blood glucose control before pregnancy and the lack of proper treatment for multiple complications including nephropathy, a multidisciplinary consultation at an external hospital recommended termination of the pregnancy. However, the patient was determined to continue the pregnancy and was referred to Peking University First Hospital. Through strict blood glucose control, monitoring and evaluation of complications, and comprehensive management, the patient's blood glucose and blood pressure were well controlled during pregnancy. Regular monitoring of urine protein, renal function, and ocular fundus was conducted. At 31 weeks and 4 days of gestation, the patient's 24-hour urine protein significantly increased. After promoting fetal lung maturity, a cesarean section was performed at 34 weeks and 1 day of gestation, resulting in a successful delivery with good maternal and neonatal outcomes. At the 42-day postpartum follow-up, the patient's blood glucose and blood pressure were stable, urine protein returned to pre-pregnancy levels, and the infant was in good general condition.

Ferroptosis is an emerging form of regulated cell death characterized by iron-dependent lipid peroxidation and the failure of the antioxidant system，which results in iron-dependent oxidative damage to the cell membrane. Ferroptosis is implicated in various biological processes，including cell proliferation，aging，and differentiation. The regulation of oxidative stress by ferroptosis is closely associated with the inactivation of glutathione peroxidase 4（Gpx4），dysfunction of the cysteine/glutamate antiporter System Xc-，the production of reactive oxygen species derived from oxidized polyunsaturated fatty acids，and alterations in lipid metabolism. Oxidative stress is a critical mechanism underlying the onset and progression of benign prostatic hyperplasia（BPH）and plays a pivotal role in its pathogenesis. Ferroptosis may regulate the occurrence and development of BPH by mediating lipid oxidative stress response.

In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.