Objective 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.Methods 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.Results 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).Conclusion 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.

Objective To observe the efficacy and safety of mechanical thrombectomy in acute ischemic stroke patients after vertebral-basilar artery stent implantation.Methods From May 2018 to October 2022,patients with acute vertebral basilar artery occlusion who underwent mechanical thrombectomy were retrospectively analyzed.The patients were divided into two groups:stent occlusion group and acute atherosclerotic stenosis occlusion(ICAS)group.The baseline characteristics of the two groups were balanced by propensity score matching method.The successful recanalization rate,90-day good outcome rate,90-day mortality rate,and symptomatic intracranial hemorrhage rate were compared.Results We enrolled 107 patients,with 14 cases in stent occlusion group and 93 cases in ICAS group.We analyzed 14 pairs by propensity score matching,including 14 cases in stent occlusion group and 27 cases in ICAS group.The successful recanalization rate and 90-day good outcome rate was lower in stent occlusion group than in ICAS group[(78.6％(11/14)vs.100％(27/27),P=0.062,28.6％(4/14)vs.44.4％(12/27),X2=0.976,P=0.323],but there was no statistical difference.The 90-day mortality rate in the stent occlusion group was significantly higher than that in the ICAS group[57.1％(8/14)vs.25.9％(7/27),x2=3.873,P=0.049].The incidence of symptomatic intracranial hemorrhage was higher in the stent occlusion group than in the ICAS group,with no statistical difference[35.7％(5/14)vs.14.8％(4/27),x2=1.289,P=0.256].Conclusion The successful recanalization rate,90-day good outcome rate,and incidence of symptomatic intracranial hemorrhage in stent occlusion group did not significantly differ from those in ICAS group,but the 90-day mortality rate was significantly higher in the former group.

Objective:To describe the current status of responsive caregiving behavior of infant mothers,to analyze their influencing factors and pathways using the information-motivation-behavioral skills(IMB)model,and to provide a basis for further interventions related to responsive caregiving be-haviors and comprehensive promotion of early childhood development.Methods:This study was a cross-sectional survey using convenience sampling.Questionnaires were used to collect basic information about mothers and their infants,as well as data on mothers' responsive caregiving behavior,knowledge of re-sponsive caregiving,social support,and parenting self-efficacy.Multivariate linear regression models were employed to analyze the influencing factors of responsive caregiving behavior,and structural equa-tion modeling was used to analyze the pathways of these influencing factors.The criterion for inadequate responsive caregiving is defined as scores not exceeding the lower quartile(P25)of the total score.Results:Among 510 mothers of aged 0-12 months infants in Weifang City,the average score for respon-sive caregiving behavior was 16.41±3.99.The proportion of inadequate responsive caregiving was 25.7％.Mothers in the insufficient responsive caregiving group had lower scores in knowledge(7.70±1.41),social support(57.92±15.16),and parenting self-efficacy(30.36±6.48)compared with those in the sufficient group,with statistically significant differences(P＜0.001).Logistic regres-sion analysis indicated that the influencing factors for responsive caregiving included the level of know-ledge about responsive parenting[adjusted OR(aOR)=0.795,95％CI:0.566-0.838],social support(aOR=0.979,95％CI:0.961-0.996),and parenting self-efficacy(aOR=0.894,95％CI:0.857-0.932).Structural equation modeling revealed that knowledge of responsive caregiving(β=0.089,P=0.031),social support(β=0.153,P=0.001),and parenting self-efficacy(β=0.296,P＜0.001)were directly related to responsive caregiving behavior.Additionally,knowledge of responsive caregiving indirectly affected responsive caregiving behavior through parenting self-efficacy(β=0.095,P=0.014),and social support indirectly affected responsive caregiving behavior through parenting self-efficacy(β=0.497,P＜0.001).Conclusion:The current level of responsive caregiving behavior among mothers of 0-1-year-old infants in Weifang City is not satisfactory.Future development of responsive care-giving interventions should focus on providing caregivers with relevant knowledge of responsive caregiving based on their needs.Additionally,it is essential to offer social support from multiple aspects to enhance caregivers' parenting self-efficacy,thereby promoting improvements in responsive caregiving behavior.

Objective:To evaluate the efficacy and long-term outcomes of fludarabine, cyclophosphamide, and rituximab (FCR) in treatment-na?ve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) .Methods:Clinical data from 68 CLL/SLL patients treated with FCR at Jiangsu Province Hospital (August 2008–May 2021) were retrospectively analyzed to assess efficacy, safety, and survival outcomes.Results:Among 68 patients [46 males, 22 females; median age 55 (47, 60) years], 13.1% (8/61) had a complex karyotype, 32.3% (20/62) had immunoglobulin heavy variable region mutated (IGHV-M) type, 6.6% (4/61) had del (17p), and 14.8% (8/54) had del (11q). Patients received a median of 6 (4, 6) FCR cycles. The overall response rate was 88.2% (60/68), including 47.0% (32/68) complete remissions. Over a median follow-up of 82 (59, 98) months, 66.2% (45/68) experienced disease progression. Median progression-free survival was 56 (21, 123) months, while median overall survival was not reached. The 5- and 10-year PFS rates were 42.6% (95% CI: 31.9–56.8% ) and 28.7% (95% CI: 19.0–43.4% ), respectively. Poor PFS was associated with del (17p) ( HR=5.04, 95% CI: 1.72–14.74, P=0.003), del (11q) ( HR=5.27, 95% CI: 2.11–13.15, P<0.001), IGHV unmutated (IGHV-UM) ( HR=4.11, 95% CI: 1.72–9.79, P=0.001), complex karyotype (CK) ( HR=3.53, 95% CI: 1.58–7.85, P=0.002), β 2-microglobulin >3.5 mg/L ( HR=2.87, 95% CI: 1.37–6.01, P=0.005). In multivariate analysis, IGHV-UM remained an independent predictor of PFS ( HR=8.63, 95% CI: 1.09–68.40, P=0.042). Sixteen patients with IGHV-M and lacking del (17p) or CK had a median PFS of 123 (58,123) months and a 5-year PFS rate of 70.7% (95% CI: 49.7–99.1% ), reaching a plateau after 5 years with no recurrences by 10 years. Common grade 3–4 adverse events included hematologic toxicity (44.1%, 30/68), infection (36.7%, 25/68), and liver dysfunction (4.4%, 3/68). Among 25 patients receiving single-agent BTK inhibitors after FCR progression, median follow-up was 45 (26, 64) months; 36% (9/25) experienced disease progression, with a median PFS time of 55 (27, 55) months. Conclusion:First-line FCR provides durable long-term benefits for patients with IGHV-M CLL without del (17p) or CK.

Objective To analyze the current quality of treatment for hospitalized cancer patients in Bei-jing,identify major issues in treatment practices,and propose improvements.Methods Nine hospitals in Beijing were selected for examination.Expert on-site interviews and medical record sampling were conducted.The"Bei-jing Cancer Diagnosis and Treatment Quality Control Checklist"was used to assess the hardware,management,anti-cancer drug therapy,radiation therapy,and surgical treatment during cancer treatment at these hospitals from January to October 2023.The relevant problems were analyzed.Results Among the nine hospitals,two(22.2％)were equipped with laminar flow rooms,and three(33.3％)had intravenous drug preparation centers.In terms of institutional management,seven hospitals(77.8％)had standardized anti-cancer drug prescription authority management,eight(88.9％)had complete emergency plans,and five(55.6％)had oncology specialist pharmacists.Regarding anti-cancer drug therapy,the areas with higher completion rates included pathology diag-nosis support(97.6％),routine pre-treatment examinations(96.3％),adverse reaction evaluation(92.7％),discharge summaries(95.1％),and admission records(91.5％).However,the accuracy of tumor staging before treatment(70.7％)and the evaluation of therapeutic efficacy after drug treatment(76.9％)needed improvement.The oncology specialty significantly outperformed the non-oncology specialty in terms of the accuracy rate of TNM staging(86.0％vs.46.9％,P＜0.001),the completeness of informed consent forms(100％vs.68.8％,P＜0.001),the completeness of drug indication evaluation(96.0％vs.78.1％,P=0.025),the completeness of admission medical history records(98.0％vs.81.3％,P=0.008),the rationality of drug dosage(96.0％vs.75.0％,P=0.005),the rationality of drug infusion time(100％vs.62.5％,P＜0.001),and the rationality of the order of drug infusion(100％vs.87.5％,P=0.010).Although the quality of radiation therapy was high,the subsequent evaluation of therapeutic efficacy(39.3％)requires enhancement.In surgical treatment,the preoper-ative pathology diagnosis support rate(78.1％)and the accuracy of tumor staging(37.5％)were relatively low,indicating issues with incomplete preoperative evaluation and the absence of multidisciplinary discussions.Conclusions There remains significant room for improvement in the quality of cancer treatment in China.It is recommended to standardize tumor staging assessment processes,strengthen entry assessments for non-oncology departments,promote the implementation of multidisciplinary treatment models,and establish a multi-department collaborative management model.Continuous monitoring of cancer diagnosis and treatment quality indicators is es-sential to promote ongoing improvements in cancer treatment quality.

Objective To observe the efficacy and safety of mechanical thrombectomy in acute ischemic stroke patients after vertebral-basilar artery stent implantation.Methods From May 2018 to October 2022,patients with acute vertebral basilar artery occlusion who underwent mechanical thrombectomy were retrospectively analyzed.The patients were divided into two groups:stent occlusion group and acute atherosclerotic stenosis occlusion(ICAS)group.The baseline characteristics of the two groups were balanced by propensity score matching method.The successful recanalization rate,90-day good outcome rate,90-day mortality rate,and symptomatic intracranial hemorrhage rate were compared.Results We enrolled 107 patients,with 14 cases in stent occlusion group and 93 cases in ICAS group.We analyzed 14 pairs by propensity score matching,including 14 cases in stent occlusion group and 27 cases in ICAS group.The successful recanalization rate and 90-day good outcome rate was lower in stent occlusion group than in ICAS group[(78.6％(11/14)vs.100％(27/27),P=0.062,28.6％(4/14)vs.44.4％(12/27),X2=0.976,P=0.323],but there was no statistical difference.The 90-day mortality rate in the stent occlusion group was significantly higher than that in the ICAS group[57.1％(8/14)vs.25.9％(7/27),x2=3.873,P=0.049].The incidence of symptomatic intracranial hemorrhage was higher in the stent occlusion group than in the ICAS group,with no statistical difference[35.7％(5/14)vs.14.8％(4/27),x2=1.289,P=0.256].Conclusion The successful recanalization rate,90-day good outcome rate,and incidence of symptomatic intracranial hemorrhage in stent occlusion group did not significantly differ from those in ICAS group,but the 90-day mortality rate was significantly higher in the former group.

Objective:To describe the current status of responsive caregiving behavior of infant mothers,to analyze their influencing factors and pathways using the information-motivation-behavioral skills(IMB)model,and to provide a basis for further interventions related to responsive caregiving be-haviors and comprehensive promotion of early childhood development.Methods:This study was a cross-sectional survey using convenience sampling.Questionnaires were used to collect basic information about mothers and their infants,as well as data on mothers' responsive caregiving behavior,knowledge of re-sponsive caregiving,social support,and parenting self-efficacy.Multivariate linear regression models were employed to analyze the influencing factors of responsive caregiving behavior,and structural equa-tion modeling was used to analyze the pathways of these influencing factors.The criterion for inadequate responsive caregiving is defined as scores not exceeding the lower quartile(P25)of the total score.Results:Among 510 mothers of aged 0-12 months infants in Weifang City,the average score for respon-sive caregiving behavior was 16.41±3.99.The proportion of inadequate responsive caregiving was 25.7％.Mothers in the insufficient responsive caregiving group had lower scores in knowledge(7.70±1.41),social support(57.92±15.16),and parenting self-efficacy(30.36±6.48)compared with those in the sufficient group,with statistically significant differences(P＜0.001).Logistic regres-sion analysis indicated that the influencing factors for responsive caregiving included the level of know-ledge about responsive parenting[adjusted OR(aOR)=0.795,95％CI:0.566-0.838],social support(aOR=0.979,95％CI:0.961-0.996),and parenting self-efficacy(aOR=0.894,95％CI:0.857-0.932).Structural equation modeling revealed that knowledge of responsive caregiving(β=0.089,P=0.031),social support(β=0.153,P=0.001),and parenting self-efficacy(β=0.296,P＜0.001)were directly related to responsive caregiving behavior.Additionally,knowledge of responsive caregiving indirectly affected responsive caregiving behavior through parenting self-efficacy(β=0.095,P=0.014),and social support indirectly affected responsive caregiving behavior through parenting self-efficacy(β=0.497,P＜0.001).Conclusion:The current level of responsive caregiving behavior among mothers of 0-1-year-old infants in Weifang City is not satisfactory.Future development of responsive care-giving interventions should focus on providing caregivers with relevant knowledge of responsive caregiving based on their needs.Additionally,it is essential to offer social support from multiple aspects to enhance caregivers' parenting self-efficacy,thereby promoting improvements in responsive caregiving behavior.

Objective:To evaluate the efficacy and long-term outcomes of fludarabine, cyclophosphamide, and rituximab (FCR) in treatment-na?ve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) .Methods:Clinical data from 68 CLL/SLL patients treated with FCR at Jiangsu Province Hospital (August 2008–May 2021) were retrospectively analyzed to assess efficacy, safety, and survival outcomes.Results:Among 68 patients [46 males, 22 females; median age 55 (47, 60) years], 13.1% (8/61) had a complex karyotype, 32.3% (20/62) had immunoglobulin heavy variable region mutated (IGHV-M) type, 6.6% (4/61) had del (17p), and 14.8% (8/54) had del (11q). Patients received a median of 6 (4, 6) FCR cycles. The overall response rate was 88.2% (60/68), including 47.0% (32/68) complete remissions. Over a median follow-up of 82 (59, 98) months, 66.2% (45/68) experienced disease progression. Median progression-free survival was 56 (21, 123) months, while median overall survival was not reached. The 5- and 10-year PFS rates were 42.6% (95% CI: 31.9–56.8% ) and 28.7% (95% CI: 19.0–43.4% ), respectively. Poor PFS was associated with del (17p) ( HR=5.04, 95% CI: 1.72–14.74, P=0.003), del (11q) ( HR=5.27, 95% CI: 2.11–13.15, P<0.001), IGHV unmutated (IGHV-UM) ( HR=4.11, 95% CI: 1.72–9.79, P=0.001), complex karyotype (CK) ( HR=3.53, 95% CI: 1.58–7.85, P=0.002), β 2-microglobulin >3.5 mg/L ( HR=2.87, 95% CI: 1.37–6.01, P=0.005). In multivariate analysis, IGHV-UM remained an independent predictor of PFS ( HR=8.63, 95% CI: 1.09–68.40, P=0.042). Sixteen patients with IGHV-M and lacking del (17p) or CK had a median PFS of 123 (58,123) months and a 5-year PFS rate of 70.7% (95% CI: 49.7–99.1% ), reaching a plateau after 5 years with no recurrences by 10 years. Common grade 3–4 adverse events included hematologic toxicity (44.1%, 30/68), infection (36.7%, 25/68), and liver dysfunction (4.4%, 3/68). Among 25 patients receiving single-agent BTK inhibitors after FCR progression, median follow-up was 45 (26, 64) months; 36% (9/25) experienced disease progression, with a median PFS time of 55 (27, 55) months. Conclusion:First-line FCR provides durable long-term benefits for patients with IGHV-M CLL without del (17p) or CK.

Objective To explore the effect of physical exercise on semen quality in order to provide basic data and theoretical basis for the improvement of male reproductive health.Methods A cross-sectional study was conducted on 1 059 males who visited the Reproductive Medicine Center of Shandong Maternal and Child Health Hospital for medical treatment and physical examination during July 2022 and April 2023.Their demographic data and physical exercise data were surveyed with questionnaires.Total sperm count,sperm concentration,total sperm motility,forward movement and normal sperm morphology were analyzed with computer aided analysis.Logistic regression model and multiple linear regression model were applied to analyze the effects of physical exercise on semen quality.Results After adjustment for confounding factors such as age,body mass index,alcohol consumption and smoking,logistic regression analysis showed that the risk of abnormal semen quality was increased in patients with moderate and heavy exercise intensity(OR=2.103,OR=2.229).Compared with the participants with physical exercise ≤10 min per session,those with＞20 min per session had a lower risk of abnormal semen quality(OR=0.357,0.256,0.289 for exercise time for＞20～30,＞30～60,＞60 min,respectively).There was no statistical significance between physical exercise frequency and semen quality(P＞0.05).The participants having exercise well were at a lower risk for abnormal semen quality(OR=0.711).Multiple linear regression analysis revealed that the frequency of physical exercise was an influencing factor of sperm concentration(β=7.474,95％CI:4.800～10.149,P＜0.05);the time of physical exercise per session was an influencing factor for total sperm count(β=20.632,95％CI:7.634～33.629);the intensity of physical exercise(β=-1.461,95％CI:-2.392～-0.530)and time of physical exercise per session(β=2.608,95％CI:1.404～3.812,P＜0.05)were influencing factors for percentage of forward motility sperm(P＜0.05);and physical exercise intensity(β=-1.934,95％CI:-3.238～-0.630),time of physical exercise per session(β=4.211,95％CI:2.525～5.897)and frequency of physical exercise(β=-2.008,95％CI:-3.480～-0.536)were influencing factors of total sperm motility(P＜0.05).Conclusion Physical exercise may affect semen quality,greater intensity of physical exercise may be a risk factor for abnormal semen quality,and longer physical exercise time may be related to improving semen quality.Therefore,proper physical exercise can help improve semen quality.

Objective To explore the role and mechanism of RNA demethylase fat mass and obesity-associated protein(FTO)in the ferroptosis in testicular interstitial cells induced by di(2-ethylhexyl)phthalate(DEHP).Methods Forty 3-week-old C57BL/6 male mice were randomly divided into a control group(corn oil)and 3 dosed DEHP treatment groups(5,250 and 500 mg/kg),and received an intragastric infusion of corresponding agents for 35 d,respectively.After mouse testicular interstitial TM3 cells was treated with 0,100,200 and 400 μmol/L mono-2-ethylhexyl phthalate(MEHP)for 24 h,corresponding plasmids were transfected to construct Fto overexpressing TM3 cells.Serum testosterone level was detected by ELISA,expression of testicular proteins was detected with immunohistochemical assay,and contents of Fe2+,malondialdehyde(MDA)and lipid peroxides in the testicle were detected by colorimetry.Methylated RNA immunoprecipitation,RT-PCR,and Western blotting were used to detect the level of N6-methyladenosine(m6A)modification.Results In the mice exposed to 250 and 500 mg/kg DEHP,the serum testosterone level was significantly reduced(P＜0.01),contents of Fe2+,MAD and lipid peroxides in testicular tissue were obviously increased(P＜0.01),and protein levels of RNA demethylase FTO,and ferroptosis related molecules ferritin heavy chain 1(FTH1)and glutathione peroxidase 4(GPX4)were significantly down-regulated(P＜0.05),while those of transferrin receptor(TFRC),ferroportin(FPN),cyclooxygenase-2(COX-2),and acyl-CoA synthetase long-chain family member 4(ACSL4)were notably up-regulated(P＜0.05).MEHP treatment for 24 h resulted in remarkably decreased cell viability in the TM3 cells,increased production of intracellular reactive oxygen species(ROS),reduced mitochondrial membrane potential(MMP)(P＜0.01),down-regulated mRNA and protein levels of Fto(P＜0.01),and the changes in other ferroptosis related proteins were consistent with the trend in testicular tissue,indicating ferroptosis in testicular interstitial cells.Intervention with ferroptosis inhibitor Fer-1 or overexpression of Fto significantly inhibited MEHP-induced toxicity and ferroptosis in TM3 cells(P＜0.05),and overexpression of Fto reduced the m6A modification of Gpx4 and Fth1 mRNA(P＜0.05).Conclusion Abnormal m6A modification of Gpx4 and Fth1 caused by inhibiting FTO expression may be the mechanism of ferroptosis in testicular interstitial cells induced by DEHP.