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 analyze the clinicopathological characterization of primary esophageal benign tumor (EBT). Methods:A total of 1,058 EBTs were enrolled from 500,000 cases in an esophageal and cardiac tumor biological sample and clinical information data-base of Henan Key Laboratory for Esophageal Cancer Research (1973-2015) in the First Affiliated Hospital of Zhengzhou University. SPSS 21.0 software was applied for data analysis. Results:In this database, 1,058 cases with primary EBTs among the 249,246 esopha-geal tumor patients with detailed clinical and pathological information were identified with an incidence of 0.42%(1,058/249,246). A total of 544 patients were male with an average age of 50±11 years old, whereas 514 patients were female, with an average age of 52± 11 years old. Among the 10 types of EBTs, leiomyoma was the most common type (84.50%, 894/1,058), followed by papilloma (6.90%, 73/1058). Adenoma (0.38%, 4/1,058) was the rarest type. Leiomyoma, gastrointestinal stromal tumor, and neurofibroma mainly oc-curred in male patients. By contrast, lipoma, granulosa cell tumor, schwannoma, and hemangioma mainly occurred in female patients.All five cases of hamartoma occurred only in female patients. Given the incidence of≥50%as the common standard, the common EBT in sequence in young male patients was leiomyoma and gastrointestinal stromal tumor, whereas that in young female patients was granulosa cell tumor and lipoma. The common EBT in sequence in older male patients was papilloma, gastrointestinal stromal tumor, and leiomyoma, whereas that in older female patients was schwannoma, papilloma, leiomyoma, gastrointestinal stromal tumor, and hamartoma. Additionally, lipoma, hemangioma, neurofibroma, and adenoma in male patients and neurofibroma in female patients oc-curred in older patients. The different ages of patients with EBTs (P=0.034) and leiomyoma (P=0.004) had a statistical significance. In these EBTs, leiomyoma, papilloma, gastrointestinal stromal tumor, and schwannoma mainly occurred in the middle esophagus, where-as lipoma mainly occurred in the lower esophagus. The major treatment for EBT in the present study was surgery (57.54%, 492/855), which was followed by endoscopic resection (38.01%, 325/855) and others (4.45%, 38/855). Conclusion:The incidence of EBT is low, with a couple of different histological types. Gender, age, and predilection sites are different depending on the histological types of EBTs. Surgery and endoscopic resection are the major treatment methods.

Objective To investigate the significance of monitoring P(c-a)CO2 (the gradients between transcutaneous PCO2 and arterial PCO2) in patients with septic shock.Method 31 patients with early septic shock were enrolled as the study group and 20 patients with stable hemodynamics as the control group from Fab.2013 to Sept.2014 in our Intensive Care Unit (ICU).The patients with septic shock were treated guided by early goal directed therapy (EGDT) within 6 hours since hospitalization.The differences of baseline P(c-a) CO2 levels and other index as arterial lactate (LAC) concentration between two groups and the variations of these indexes after EGDT in the study group were compared respectively.Results The baseline levels of P(c-a)CO2 and LAC in patients with septic shock were significantly higher than in patients of control group: (21.2 ± 10.1) mmHg vs.(7.5 ±4.6), P =0.000, and (4.0±2.4) mmol/ Lvs.(1.6 ± 0.5), P =0.000.The areas under receiver operator characteristic (ROC) curve (AUC) for baselineP(c-a)CO2 and LAC were 0.918 (95％ CI: 0.843-0.992) and 0.840 (95％ CI: 0.719-0.962) respectively.A threshold of 14.0 mmHg for P(c-a)CO2 and 2.1 mmol/L for LAC discriminated patients with septic shock from without shock with the same sensibility of 83.9％ and the same specificity of 90.0％, respectively.With regard to prognosis (Day 28), AUC for baseline P(c-a)CO2 and LAC were 0.739 (95％ CI: 0.562-0.917) and0.702 (95％ CI: 0.514-0.889) respectively.A threshold of 21.5 mmHg for P(c-a) CO2 and 3.9 mmol/L for LAC discriminated survivors from nonsurvivors with the same sensibility of 71.4％ and the same specificity of 70.6％ respectively.31 patients in the study group completed EGDT within 6 hours after the admission, 16 (51.6％) passed EGDT and 13 (81.3％) survived, 15 (48.4％) failed EGDT and 4 (26.7％) survived, and survival rates were significantly different, F =9.314, P =0.004.After EGDT, P(c-a) CO2 (18.8 ± 9.4) mmHg and LAC (3.3 ± 2.4) mmol/Lreduced significantly compared with the baselines, all P =0.000.AUC then for P(c-a) CO2 and LAC were 0.742 (95％ CI: 0.562-0.921) and 0.769 (95％ CI: 0.593-0.945), respectively.A threshold of 18.3 mmHg for P(c-a)CO2 and 3.1 mmol/L for LAC discriminated survivors from nonsurvivors with the same sensibility of 71.4％ and the specificity of 71.4％ and of 76.5％ respectively.P(c-a) CO2 and LAC of patients passed EGDT reduced significantly compared with those failed EGDT: (14.8 ± 7.5) mmHgvs.(23.6±9.6) mmHg (P=0.012)、 (2.5±1.5) mmol/L vs.(4.3±2.9) mmol/L (P=0.038), and so did with their baseline : (14.8±7.5) mmHgvs.(18.0±8.1) mmHg, (P=0.042)、 (2.5±1.5) mmol/Lvs.(3.2±1.8) mmol/L, P=0.043.In patients failed EGDT, P(c-a)CO2 and LAC changed little after EGDT, from (24.6 ± 9.2) to (23.6 ± 9.6) mmHg (P =0.238) and from (4.8 ± 2.5) mmol/L to (4.3 ± 2.9) mmol/L (P =0.629).When baseline levels were compared between patients passed EGDT with those failed EGDT, P(c-a) CO2 was (18.0 ±8.1) mmHg vs.(24.6 ± 9.2) mmHg (P =0.042), LAC was (3.2 ± 1.8) mmol/L vs.(4.8 ± 2.5) mmol/L (P =0.050).Conclusions P(c-a) CO2 ＞ 14.0 mmHg could play a role in recognizing early septic shock.EGDT was an effective therapy for the disease and P(c-a)CO2 level could reflect the efficacy of EGDT.P(c-a)CO2 ＞ 21.5mmHg before EGDT and P(c-a) CO2 ＞ 19.3 mmHg after EGDT both could predict the prognosis of patients with septic shock.All above correlated well with LAC and represented a new efficient technique to assess tissue microperfusion.

Objective Our study was performed to design a drug-sustained capsular tension ring (CTR) to evaluate its potentiality on prevention of PCO in the swine capsular bag model in vitro.Methods Following the continuous capsule curvilinear capsulorhexis ( CCCC),Phacomulsification with capsular tension ring implantation was pedormed.CTR-supported swine capsular bag models were prepared and divided into two groups,group CTR ( n =13 ) implanted with the original CTR without any modification and group CTR-PLGA-MG132 ( n =13) implanted with the CTR covered with PLGA and MG132.The CTRsupported capsular bags were cultured in vitro for up to 3 weeks.The area of lens epithelial cells (LEC) coverage over the posterior capsule surface was quantified every day under microscope.The capsules were treated for histological examination.The change of fibronectin was assessed by ELISA assay kit.Results After 2 ～ 3 days,outgrowth of LEC across the posterior capsule was observed,and the posterior capsule was totally covered by a confluent monolayer of cell after (9.06 ± 1.61 ) days in group CTR.Capsular wrinkles became increasingly apparent as time progressed.An increase in capsular thickness was also observed.In contrast,there was less LEC deposition in group CTR-PLGA-MG132.Histological examination showed LEC layers were closely arranged on the posterior capsular surface in group CTR.In group CTR-PLGA-MG132,there was comparatively looser cell arrangement.Compared with group CTR,the mean fibronectin level of posterior capsule by week 3 in group CTR-PLGA-MG132 was 25.14 μg/ml and 106.09 μg/ml respectively.Statistical analysis showed a significant difference ( P ＜ 0.01 ).Conclusions LEC migration,proliferation,and synthesis of EMT markers were inhibited in Group CTR-PLGA-MG132,compared with Group CTR.Drug-sustained capsular tension rings can effectively inhibit the migration,proliferation of LEC and the change of EMT ( epithelial-to-mesenchymal transition) in swine capsular bag models.Drug-sustained capsular tension rings might be a potential therapy to prevent the posterior capsular opacification in the future.