Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

Objective:To investigate the clinical efficacy of autologous costal cartilage rhinoplasty combined with costal cartilage block grafting to the alar base in the correction of saddle nose deformity with alar-columellar base depression.Methods:A retrospective analysis was performed on patients who underwent autologous costal cartilage rhinoplasty combined with alar base augmentation at the Department of Plastic Surgery, Zhejiang Provincial People’s Hospital, from January 2022 to December 2023. All patients presented with alar-columellar base depression combined with saddle nose deformity. Through bilateral marginal incisions of the lower lateral cartilage and an inverted V-shaped columellar incision, the 6th costal cartilage near the sternal end was harvested and sculpted into two alar base grafts, one columellar strut graft in an inverted V shape, two septal extension grafts, and one cap graft. On the basis of block costal cartilage grafting to the alar base, a nasal tip support framework and septal extension graft were constructed, combined with implantation of an expanded polytetrafluoroethylene (ePTFE) prosthesis, to correct the aesthetic defects of saddle nose with alar-columellar base depression. Postoperative complications and recovery were recorded. Standardized pre- and 6-month postoperative photographs were analyzed using Adobe Photoshop and Image J to measure nasal base elevation, nasolabial angle, nasofrontal angle, nasal tip angle, nasal tip projection-to-length ratio, and columella-lobule angle. Patient satisfaction was evaluated preoperatively and at 6 months postoperatively using the visual analogue scale (VAS, 0-10 points; higher scores indicate greater satisfaction) and the rhinoplasty outcome evaluation (ROE) questionnaire (total score 0-24; higher scores indicate greater satisfaction). Paired t-tests were used for statistical analysis, with P<0.05 considered statistically significant. Results:A total of 48 patients were enrolled, including 3 males and 45 females, aged from 19 to 37 years (27.3±5.9 years). The postoperative follow-up period ranged from 6 to 12 months. No infections, hemorrhage, or other complications occurred. Swelling subsided substantially within 4-5 weeks postoperatively, and no significant nasal airway obstruction, sensory abnormalities, or olfactory disturbances were observed. Patients were satisfied with their postoperative appearance and outcomes. At 6 months postoperatively, the nasal base elevation was increased compared with preoperative measurements (6.08 ± 0.85) mm. Compared with preoperative values, significant improvements were observed at 6 months postoperatively in nasolabial angle (84.69° ± 4.24° vs. 96.81° ± 5.80°), nasofrontal angle (143.91° ± 3.91° vs. 136.24° ± 2.66°), nasal tip angle (84.13° ± 5.25° vs. 78.20° ± 5.40°), nasal tip projection-to-length ratio (0.45 ± 0.05 vs. 0.53 ± 0.07), columella-lobule angle (49.22° ± 5.29° vs. 44.25° ± 3.52°), VAS score (4.69 ± 0.90 vs. 8.45 ± 0.80), and ROE score (11.99 ± 1.47 vs. 21.50 ± 1.31) (all P<0.05). Conclusion:Autologous costal cartilage rhinoplasty combined with costal cartilage block grafting to the alar base can effectively correct saddle nose deformity with alar-columellar base depression, achieving comprehensive improvement in midfacial aesthetics.

Objective To investigate the benefits and challenges of the reform in evidence-based obstetric nursing practice in clinical nursing,therefore to provide a reference for initiating and keeping the reform in evidence-based nursing practices.Methods A method of descriptive phenomenological research was conducted between January and February 2024 in our hospital on 10 selected clinical nurses by purposive sampling.An outline for interviews was developed based on literature review and expert interviews,followed by semi-structured interviews with the nurses.Core themes were extracted with Colaizzi's seven-step analysis.Results Three themes and 12 sub-themes were summarised in this study.The 3 core themes that were identified among the nurses included:acceptance of evidence-based nursing practice reform(with 3 domains regarding knowledge,decision-making and action),perception of the benefits of the reform in evidence-based nursing practice(with 5 domains regarding the professionalism and scientific nature of clinical nursing,improvement of patient experience and nursing outcomes,enhancement of nursing quality and safety,promotion of innovation in on-the-job training and education,and facilitation of collaboration within the nursing team),and perception in the challenges of reform in evidence-based nursing practice(with 4 domains regarding the stress and challenges,doubts and resistance,poor cooperation between doctors and nurses,and risks in clinical decision-making).Conclusion The acceptance regarding reform in evidence-based nursing practice varies among the nurses.It is necessary to promote the acceptance,provide the targeted guidance and intervene in the factors of benefits and challenges among the nurses,hence to facilitate a smooth implementation of the reform in evidence-based nursing practice.

OBJECTIVE To analyze the results of speech-evoked auditory brainstem response(s-ABR)tests in patients with presbycusis and explore the mechanisms of speech coding in these patients.METHODS Thirty patients with presbycusis(presbycusis group),30 elderly individuals with normal hearing(elderly normal group),and 30 young adults with normal hearing(young control group)were recruited.The s-ABR was elicited using a 40 ms duration complex speech stimulus/da/,and the characteristics of s-ABR were analyzed in each group.RESULTS The latencies of waves V and A in the presbycusis group were significantly prolonged compared to both the elderly normal group and the young control group(P<0.05).However,there was no statistically significant difference in the latencies of waves between the elderly normal group and the young control group(P>0.05).The amplitude of wave A and the slope of the V-A complex wave in the presbycusis group were significantly lower than those in the young control group(P<0.05),while no statistically significant differences were observed in the amplitudes of other waves.CONCLUSION The characteristics of s-ABR in patients with presbycusis suggest that these patients have poor synchronization in response to stimulus timing and deficiencies in coding high-frequency and rapidly changing auditory information,which may be one of the mechanisms underlying the decline in speech abilities in patients with presbycusis.

Objective:To explore the correlation between erythropoiesis-stimulating agents (ESAs) and seizures.Methods:Drug target Mendelian randomization (MR) and multivariate MR analysis were employed to evaluate the causal correlation between ESAs and seizures as well as status epilepticus. The data were sourced from published genome-wide association studies (GWAS) in the UK Biobank and Finland FinnGen databases. The instrumental variables were ESA-related single-nucleotide polymorphisms (SNPs) with F>10, the exposure factor was ESAs treatment, and outcome measures were seizures and status epilepticus. The methods of inverse variance weighted (IVW), weighted median estimator (WME) and MR-Egger regression were applied in the drug-target MR analysis, and the methods of IVW, MR-Egger regression and MR-LASSO were applied in the multivariate MR analysis. Adverse event reports from January 2004 to June 2024 in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database were collected. The signals of ESA-related seizures and status epilepticus were detected by reporting odds ratio (ROR) method and proportional reporting ratio (PRR) method. Results:A total of 15 SNPs were included in the MR analysis. Drug-target MR analysis showed that ESAs were significantly associated with the risk of seizures [IVW odds ratio ( OR)=1.575, 95% confidence interval ( CI): 1.055-2.353, P=0.026], but not associated with the risk of status epilepticus ( OR=1.818, 95 %CI: 0.403-8.207, P=0.437). Multivariate MR analysis showed that the above significant association was not found after correcting the risk factors of seizures such as stroke, pulmonary embolism, brain tumor, and dementia ( OR=0.359, 95 %CI: -0.014- 0.732, P=0.059). No risk signals of seizures and status epilepticus caused by 3 ESAs (recombinant human erythropoietin, darbepoetin alfa, methoxy polyethylene glycol-epoetin beta) were detected in FAERS database. Conclusion:ESAs may not lead to an increase in risk of seizures.

Objective:To develop the Puerperal Delivery Trauma Perception Scale and test its reliability and validity.Methods:Based on the theory of unpleasant symptoms and combining literature review, semi-structured interview, and group discussion, an item pool was created. The initial version of the scale was formed through Delphi expert consultation and pre-investigation. A convenience sampling method was used to select 304 puerperal women from seven Grade-A tertiary hospitals in Wuhan for reliability and validity testing of the scale in January and February 2024.Results:The Puerperal Delivery Trauma Perception Scale includes seven dimensions and 34 items. The Cronbach's α coefficient of the scale was 0.929, the split-half reliability was 0.874, and the test-retest reliability was 0.932. Exploratory factor analysis extracted seven common factors, with a cumulative variance contribution rate of 71.221%.Conclusions:The Puerperal Delivery Trauma Perception Scale has good reliability and validity and can be used to assess the trauma perception of puerperal women in China.

Objective To investigate the benefits and challenges of the reform in evidence-based obstetric nursing practice in clinical nursing,therefore to provide a reference for initiating and keeping the reform in evidence-based nursing practices.Methods A method of descriptive phenomenological research was conducted between January and February 2024 in our hospital on 10 selected clinical nurses by purposive sampling.An outline for interviews was developed based on literature review and expert interviews,followed by semi-structured interviews with the nurses.Core themes were extracted with Colaizzi's seven-step analysis.Results Three themes and 12 sub-themes were summarised in this study.The 3 core themes that were identified among the nurses included:acceptance of evidence-based nursing practice reform(with 3 domains regarding knowledge,decision-making and action),perception of the benefits of the reform in evidence-based nursing practice(with 5 domains regarding the professionalism and scientific nature of clinical nursing,improvement of patient experience and nursing outcomes,enhancement of nursing quality and safety,promotion of innovation in on-the-job training and education,and facilitation of collaboration within the nursing team),and perception in the challenges of reform in evidence-based nursing practice(with 4 domains regarding the stress and challenges,doubts and resistance,poor cooperation between doctors and nurses,and risks in clinical decision-making).Conclusion The acceptance regarding reform in evidence-based nursing practice varies among the nurses.It is necessary to promote the acceptance,provide the targeted guidance and intervene in the factors of benefits and challenges among the nurses,hence to facilitate a smooth implementation of the reform in evidence-based nursing practice.

Objective:To investigate the clinical efficacy of autologous costal cartilage rhinoplasty combined with costal cartilage block grafting to the alar base in the correction of saddle nose deformity with alar-columellar base depression.Methods:A retrospective analysis was performed on patients who underwent autologous costal cartilage rhinoplasty combined with alar base augmentation at the Department of Plastic Surgery, Zhejiang Provincial People’s Hospital, from January 2022 to December 2023. All patients presented with alar-columellar base depression combined with saddle nose deformity. Through bilateral marginal incisions of the lower lateral cartilage and an inverted V-shaped columellar incision, the 6th costal cartilage near the sternal end was harvested and sculpted into two alar base grafts, one columellar strut graft in an inverted V shape, two septal extension grafts, and one cap graft. On the basis of block costal cartilage grafting to the alar base, a nasal tip support framework and septal extension graft were constructed, combined with implantation of an expanded polytetrafluoroethylene (ePTFE) prosthesis, to correct the aesthetic defects of saddle nose with alar-columellar base depression. Postoperative complications and recovery were recorded. Standardized pre- and 6-month postoperative photographs were analyzed using Adobe Photoshop and Image J to measure nasal base elevation, nasolabial angle, nasofrontal angle, nasal tip angle, nasal tip projection-to-length ratio, and columella-lobule angle. Patient satisfaction was evaluated preoperatively and at 6 months postoperatively using the visual analogue scale (VAS, 0-10 points; higher scores indicate greater satisfaction) and the rhinoplasty outcome evaluation (ROE) questionnaire (total score 0-24; higher scores indicate greater satisfaction). Paired t-tests were used for statistical analysis, with P<0.05 considered statistically significant. Results:A total of 48 patients were enrolled, including 3 males and 45 females, aged from 19 to 37 years (27.3±5.9 years). The postoperative follow-up period ranged from 6 to 12 months. No infections, hemorrhage, or other complications occurred. Swelling subsided substantially within 4-5 weeks postoperatively, and no significant nasal airway obstruction, sensory abnormalities, or olfactory disturbances were observed. Patients were satisfied with their postoperative appearance and outcomes. At 6 months postoperatively, the nasal base elevation was increased compared with preoperative measurements (6.08 ± 0.85) mm. Compared with preoperative values, significant improvements were observed at 6 months postoperatively in nasolabial angle (84.69° ± 4.24° vs. 96.81° ± 5.80°), nasofrontal angle (143.91° ± 3.91° vs. 136.24° ± 2.66°), nasal tip angle (84.13° ± 5.25° vs. 78.20° ± 5.40°), nasal tip projection-to-length ratio (0.45 ± 0.05 vs. 0.53 ± 0.07), columella-lobule angle (49.22° ± 5.29° vs. 44.25° ± 3.52°), VAS score (4.69 ± 0.90 vs. 8.45 ± 0.80), and ROE score (11.99 ± 1.47 vs. 21.50 ± 1.31) (all P<0.05). Conclusion:Autologous costal cartilage rhinoplasty combined with costal cartilage block grafting to the alar base can effectively correct saddle nose deformity with alar-columellar base depression, achieving comprehensive improvement in midfacial aesthetics.

Objective:To explore the correlation between erythropoiesis-stimulating agents (ESAs) and seizures.Methods:Drug target Mendelian randomization (MR) and multivariate MR analysis were employed to evaluate the causal correlation between ESAs and seizures as well as status epilepticus. The data were sourced from published genome-wide association studies (GWAS) in the UK Biobank and Finland FinnGen databases. The instrumental variables were ESA-related single-nucleotide polymorphisms (SNPs) with F>10, the exposure factor was ESAs treatment, and outcome measures were seizures and status epilepticus. The methods of inverse variance weighted (IVW), weighted median estimator (WME) and MR-Egger regression were applied in the drug-target MR analysis, and the methods of IVW, MR-Egger regression and MR-LASSO were applied in the multivariate MR analysis. Adverse event reports from January 2004 to June 2024 in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database were collected. The signals of ESA-related seizures and status epilepticus were detected by reporting odds ratio (ROR) method and proportional reporting ratio (PRR) method. Results:A total of 15 SNPs were included in the MR analysis. Drug-target MR analysis showed that ESAs were significantly associated with the risk of seizures [IVW odds ratio ( OR)=1.575, 95% confidence interval ( CI): 1.055-2.353, P=0.026], but not associated with the risk of status epilepticus ( OR=1.818, 95 %CI: 0.403-8.207, P=0.437). Multivariate MR analysis showed that the above significant association was not found after correcting the risk factors of seizures such as stroke, pulmonary embolism, brain tumor, and dementia ( OR=0.359, 95 %CI: -0.014- 0.732, P=0.059). No risk signals of seizures and status epilepticus caused by 3 ESAs (recombinant human erythropoietin, darbepoetin alfa, methoxy polyethylene glycol-epoetin beta) were detected in FAERS database. Conclusion:ESAs may not lead to an increase in risk of seizures.

Objective:To develop the Puerperal Delivery Trauma Perception Scale and test its reliability and validity.Methods:Based on the theory of unpleasant symptoms and combining literature review, semi-structured interview, and group discussion, an item pool was created. The initial version of the scale was formed through Delphi expert consultation and pre-investigation. A convenience sampling method was used to select 304 puerperal women from seven Grade-A tertiary hospitals in Wuhan for reliability and validity testing of the scale in January and February 2024.Results:The Puerperal Delivery Trauma Perception Scale includes seven dimensions and 34 items. The Cronbach's α coefficient of the scale was 0.929, the split-half reliability was 0.874, and the test-retest reliability was 0.932. Exploratory factor analysis extracted seven common factors, with a cumulative variance contribution rate of 71.221%.Conclusions:The Puerperal Delivery Trauma Perception Scale has good reliability and validity and can be used to assess the trauma perception of puerperal women in China.