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 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 anatomic mechanism and risk factors of intracranial embolism caused by injection at temporal region.Methods:(1) Latex perfusion was performed on the vessels of 8 cranial specimens. The vessels from the superficial temporal artery to the carotid artery were dissected to measure the length, the diameter of starting point and ending point and the volume of vessels (drainage method). (2) Cranial CT angiography of 20 patients (excluding patients with cervical diseases) were obtained from the database of Zhejiang Provincial People’s Hospital from January 2021 to December 2022. The length, the diameter of starting point and ending point, and the volume of vessels were measured. (3) 5 plastic surgeons used pressure simulation measuring equipment to vigorously press the temporal region of the real skull model according to the clinical practice and maintain 2 s to obtain the maximum pressure value. The additional pressure on the temporal region was obtained by subtracting the common carotid artery base pressure [set at 90, 120, 150 and 200 mmHg (1 mmHg = 0.133 kPa)] from the maximum pressure.Results:(1) 8 arteries were collected from 4 skull specimens. The length of vessels was (169.5±7.2) mm, the diameter of the starting point of vessel was (4.29±0.28) mm, the diameter of the ending point of vessel was (1.31±0.15) mm, and the volume was (1.56±0.21) ml. (2) There were 11 males and 9 females among 20 patients aged 23-53 years. The length of vessels was (172.2±7.6) mm, the diameter of the starting point of vessel was (5.63±0.43) mm, the diameter of the ending point of vessel was (1.77±0.16) mm, and the volume was (1.59±0.23) ml. (3) The mean value of additional pressure generated by local pressure on the temporal region by 5 physicians was (127.2±10.1) mmHg (113.8-138.6 mmHg).Conclusion:When the injection volume into the superficial temporal artery was more than 1.6 ml, the artery was damaged, and the temporal area was pressed strongly (the local pressure was more than 110 mmHg above the basic pressure), the injection material might flow into the intracranial from the junction of the common carotid artery and into the internal carotid artery, which was the possible mechanism of the temporal filling leading to intracranial embolism.

Objective:To investigate the anatomic mechanism and risk factors of intracranial embolism caused by injection at temporal region.Methods:(1) Latex perfusion was performed on the vessels of 8 cranial specimens. The vessels from the superficial temporal artery to the carotid artery were dissected to measure the length, the diameter of starting point and ending point and the volume of vessels (drainage method). (2) Cranial CT angiography of 20 patients (excluding patients with cervical diseases) were obtained from the database of Zhejiang Provincial People’s Hospital from January 2021 to December 2022. The length, the diameter of starting point and ending point, and the volume of vessels were measured. (3) 5 plastic surgeons used pressure simulation measuring equipment to vigorously press the temporal region of the real skull model according to the clinical practice and maintain 2 s to obtain the maximum pressure value. The additional pressure on the temporal region was obtained by subtracting the common carotid artery base pressure [set at 90, 120, 150 and 200 mmHg (1 mmHg = 0.133 kPa)] from the maximum pressure.Results:(1) 8 arteries were collected from 4 skull specimens. The length of vessels was (169.5±7.2) mm, the diameter of the starting point of vessel was (4.29±0.28) mm, the diameter of the ending point of vessel was (1.31±0.15) mm, and the volume was (1.56±0.21) ml. (2) There were 11 males and 9 females among 20 patients aged 23-53 years. The length of vessels was (172.2±7.6) mm, the diameter of the starting point of vessel was (5.63±0.43) mm, the diameter of the ending point of vessel was (1.77±0.16) mm, and the volume was (1.59±0.23) ml. (3) The mean value of additional pressure generated by local pressure on the temporal region by 5 physicians was (127.2±10.1) mmHg (113.8-138.6 mmHg).Conclusion:When the injection volume into the superficial temporal artery was more than 1.6 ml, the artery was damaged, and the temporal area was pressed strongly (the local pressure was more than 110 mmHg above the basic pressure), the injection material might flow into the intracranial from the junction of the common carotid artery and into the internal carotid artery, which was the possible mechanism of the temporal filling leading to intracranial embolism.

Objective:To investigate the clinical effect of "mutual support" framework in costal cartilage rhinoplasty.Methods:From June 2020 to December 2021, the patients were enrolled and undergone rhinoplasty with bilateral lower lateral cartilage margin incision combined with nasal columnar incision in the Department of Plastic & Reconstructive Surgery of Zhejiang Provincial People’s Hospital. During the operation, the sixth costal cartilage was made into the nasal columella support graft(strut) and the nasal tip graft integrated scaffold, and the septal extension grafts (SEG). The strut and SEG were sutured in the same plane to construct the framework to correct the aesthetic defects of the nose. Abode Photoshop CS 6.0 was used to measure a series of aesthetics index before and 6 months after surgery, including nasofrontal angle, nasorostral angle, nasolabial angle, columella lobular angle, ratio of tip projection to the length of the nose and ratio of the length of the infratip lobule to the length of the nasal columella to evaluate the surgical effect. Visual analogue scale (VAS) and rhinoplasty outcome evaluation (ROE) were used to investigate the patients’ satisfaction. Paired t-test was used for data analysis and P<0.05 was considered statistically significant. Results:A total of 53 patients were enrolled, including 4 males and 49 females, aged from 18 to 45 years (average age: 25.6 years). Forty-nine cases were primary rhinoplasty and 4 cases were secondary rhinoplasty. No short-term complications including hemorrhage and infection occurred in 53 patients. All patients were followed up for 6-12 months. There were statistically significant differences in nasofrontal angle, nasorostral angle, nasolabial angle, columella lobular angle, ratio of tip projection to the length of the nose and ratio of the length of the infratip lobule to the length of the nasal columella( P<0.01), which sugguested that aesthetic defects of the nose were corrected and no obvious deflection and rotation of nasal tip occured. VAS score and ROE score postoperatively were 7.6±0.4 and 21.3±2.1, respectively, which were significantly higher than preoperatively( 6.1±0.5, 10.5±1.6)( P< 0.01). Postoperative satisfaction survey showed that swelling disappeared within 4-6 weeks after surgery, and no obvious ventilatory disorder, paresthesia and hyposmia symptoms occurred. Most patients were satisfied with the aesthetic and functional results. Conclusions:The "mutual support" framework in costal cartilage rhinoplasty can reduce the risk of framework deflection and nasal tip rotation and obtain satisfactory nasal columella shape.

Objective:To investigate the clinical effect of "mutual support" framework in costal cartilage rhinoplasty.Methods:From June 2020 to December 2021, the patients were enrolled and undergone rhinoplasty with bilateral lower lateral cartilage margin incision combined with nasal columnar incision in the Department of Plastic & Reconstructive Surgery of Zhejiang Provincial People’s Hospital. During the operation, the sixth costal cartilage was made into the nasal columella support graft(strut) and the nasal tip graft integrated scaffold, and the septal extension grafts (SEG). The strut and SEG were sutured in the same plane to construct the framework to correct the aesthetic defects of the nose. Abode Photoshop CS 6.0 was used to measure a series of aesthetics index before and 6 months after surgery, including nasofrontal angle, nasorostral angle, nasolabial angle, columella lobular angle, ratio of tip projection to the length of the nose and ratio of the length of the infratip lobule to the length of the nasal columella to evaluate the surgical effect. Visual analogue scale (VAS) and rhinoplasty outcome evaluation (ROE) were used to investigate the patients’ satisfaction. Paired t-test was used for data analysis and P<0.05 was considered statistically significant. Results:A total of 53 patients were enrolled, including 4 males and 49 females, aged from 18 to 45 years (average age: 25.6 years). Forty-nine cases were primary rhinoplasty and 4 cases were secondary rhinoplasty. No short-term complications including hemorrhage and infection occurred in 53 patients. All patients were followed up for 6-12 months. There were statistically significant differences in nasofrontal angle, nasorostral angle, nasolabial angle, columella lobular angle, ratio of tip projection to the length of the nose and ratio of the length of the infratip lobule to the length of the nasal columella( P<0.01), which sugguested that aesthetic defects of the nose were corrected and no obvious deflection and rotation of nasal tip occured. VAS score and ROE score postoperatively were 7.6±0.4 and 21.3±2.1, respectively, which were significantly higher than preoperatively( 6.1±0.5, 10.5±1.6)( P< 0.01). Postoperative satisfaction survey showed that swelling disappeared within 4-6 weeks after surgery, and no obvious ventilatory disorder, paresthesia and hyposmia symptoms occurred. Most patients were satisfied with the aesthetic and functional results. Conclusions:The "mutual support" framework in costal cartilage rhinoplasty can reduce the risk of framework deflection and nasal tip rotation and obtain satisfactory nasal columella shape.

Objective:To explore predictors of overall survival (OS) in Chinese patients with polycythemia vera (PV) .Methods:A total of 906 consecutive newly diagnosed patients with PV seen at the Blood Diseases Hospital, Chinese Academy of Medical Sciences, from June 2007 to February 2020 were included, and their data were collected. PV was diagnosed according to 2016 World Health Organization (WHO) diagnostic definitions. OS and prognostic factors were retrospectively analyzed.Results:Among the 906 patients, 439 were male (48.5%) and 467 were female (51.5%) . The median age was 57 years (range: 18-91 years) . 31.6% (276/874) of the patients had a thrombosis history at diagnosis, and 4.6% (25/541) of the patients had abnormal cytogenetics. The median follow-up was 54 months (95% confidence interval [ CI] 8-130 months) . The 5- and 10-year cumulative deaths were 5.8% (95% CI 4.8%-6.7%) and 11.1% (95% CI 9.3%-12.9%) , respectively. Univariate analysis showed that age ≥60 years, thrombosis history, white blood cells (WBC) ≥15×10 9/L, platelet (PLT) ≥450×10 9/L, and platelet distribution width (PDW) ≥15 fl significantly correlated with worse OS, and palpable spleen correlated with better OS. Multivariate analysis showed that age ≥60 years ( HR=4.3, 95% CI 2.1-9.2, P<0.001) and PDW ≥15 fl ( HR=2.1, 95% CI 1.1-4.0, P=0.023) were independent prognostic factors for worse OS. The 5-year cumulative death for patients with PDW ≥15 fl or PDW<15 fl was 8.6% (95% CI 5.9%-11.3%) or 4.4% (95% CI 3.4%-5.4%) , respectively. The 5-year cumulative death for patients defined as low-, intermediate-, and high-risk patients by international working group score system for PV (IWG-PV) were 0.8% (95 CI 0.2%-1.4%) , 4.0% (95% CI 2.7%-5.3%) , and 12% (95% CI 9.6%-14.4%) , respectively, with a significant difference among the three cohorts ( P<0.05) . PDW ≥ 15 fl significantly affected OS for intermediate- and high-risk patients ( HR=2.3, 95% CI 1.2-4.2, P=0.009) defined by IWG-PV score system, but not for low-risk patients ( HR=3.1, 95% CI 0.2-52.0, P=0.405) . Conclusions:Age ≥60 years and PDW ≥15 fl were independent prognostic factors for worse OS in PV. IWG-PV score system effectively predicted OS for Chinese patients with PV.

Objective To study the prevalence situation of chronic diseases among teachers from some middle and primary schools in Chongqing City.Methods The physical examination data of 6969 teachers in 52 middle and primary schools in a district of Chongqing major city were collected.The survey data of overweight,obesity,hyperlipidemia,osteoporosis,fatty liver and hyperuricemia were statistically analyzed.Results The total morbidity rates of overweight,obesity,hyperlipidemia,osteoporosis,fatty liver and hyperuricemia were 31.3 ％,7.5 ％,35.1％,34.7 ％,22.4 ％ and 22.2 ％ respectively.The incidence rates of above diseases had difference among the age periods of ≤44 year old,＞44 ＜60 years old and ≥60 year old (P＜0.05).The incidence rate was significantly increased with age increase (P＜0.05).The incidence rate of osteoporosis in females was higher than that in males(P＜ 0.01);while the incidence rate of fatty liver and hyperuricemia in males were higher that in females (P＜0.01).Conclusion The incidence of chronic diseases among teachers in middle and primary schools is worth attention.Therefore it is necessary to carry out the health education aiming at the teacher population characteristics,strengthen their heath management and behavior intervention for increasing their health level.

Objective To compare the sensitivity of four kinds of drug susceptibility test method in detecting sensitivity of tigecycline against Acinetobacter baumannii.Methods The susceptibility of 72 clinically isolated strains of carbapenemase-resistant Acinetobacter baumannii(CRAB) to tigecycline in vitro was detected with disk diffusion method,VITEK 2 Compact system,E-test and MIC test strip(MTS) test strip respectively,according to FDA standards,and the differences of four kinds of drug susceptibility test methods were compared.Results The susceptibility rates of 72 strains of CRAB to tigecycline by disk diffusion method,VITEK 2 Compact system,E-test and MIC test strip were 50.00%,69.44%,36.11% and 98.61% respectively,the intermediate rates were 48.61%,29.17%,26.39% and 1.39% respectively,the resistant rates were 1.39%,1.39%,37.50% and 0.00% respectively.Compared with MTS,the classification consistency rates of E-test,disk diffusion method and VITEK 2 Compact system were 36.11%,51.39% and 70.83% respectively.Conclusion There is difference among four kinds of method for conducting the drug susceptibility testing of tigecycline against CRAB,the consistency of disk diffusion method,VITEK 2 Compact system and E-test is lower.Detecting mediation or drug resistant strains of CRAB by disk diffusion method,VITEK 2 Compact system and E-test needs to be verified by MTS or Broth dilution method.