Triple-negative breast cancer (TNBC) is a highly aggressive malignancy predominantly managed via chemotherapy. Our clinical sample analysis revealed a significant correlation between elevated CD24 expression in TNBC tumor cells and patient survival rates. We developed a novel antibody-drug conjugate (ADC), named HN03, consisting of an antibody with engineered cysteines for site-specific conjugation with a low toxic nitric oxide (NO) precursor as its payload through a novel Pt(IV)-mediated bioorthogonal self-cleavable linker. HN03 specifically targets tumor cells expressing high levels of CD24, concurrently generating cisplatin and releasing NO upon activation. HN03 also exhibited potent in vitro and in vivo antitumor activity. It significantly reduced tumor growth at various doses, prevented tumor metastasis, with markedly lower toxicity than traditional chemotherapy agents. We found that a key mechanism of its action involved inducing apoptosis and endoplasmic reticulum stress, substantially decreasing the number of M2-type macrophages. Overall, HN03 stands out as a promising therapeutic option for TNBC, offering a targeted treatment with reduced side effects and the potential for improved outcomes. Furthermore, using Pt(IV) in the linker and an NO precursor as the payload enhances the versatility of the Antibody-NO donor Conjugate (ANC), offering new avenues for the design of the next generation of ADCs.

Objective:To explore the heterogeneity of alienation among adolescents and examine the impact of child psychological maltreatment, childhood bullying, online social exclusion, and demographic variables.Methods:In October 2023, the alienation scale was administered to 1 316 adolescents. Latent profile analysis was conducted using Mplus 8.3, and multinomial Logistic regression analysis was performed using SPSS 26.0 to explore the factors associated with the heterogeneity of adolescent alienation.Results:(1) The score of adolescent alienation was 22.00 (17.00, 29.00). The results of latent profile analysis showed that there was heterogeneity in adolescent alienation, which could be divided into two categories as low alienation (66.79%, 879/1 316) and high alienation (33.21%, 437/1 316).(2) Binary Logistic regression analysis showed that gender ( B=0.57, OR=1.77, P<0.01), being an only child ( B=-0.34, OR=0.71, P<0.05) were significantly associated with adolescent alienation. Additionally, child psychological maltreatment( B=1.61, OR=5.02, P<0.01), childhood bullying ( B=1.09, OR=2.98, P<0.01), and online social exclusion ( B=1.64, OR=5.17, P<0.01) were identified as critical factors influencing adolescent alienation. Conclusion:There is heterogeneity in alienation among adolescents. Child psychological maltreatment, child bullying, online social exclusion and demographic variables are the main influencing factors of alienation among adolescents.

Objective:To evaluate the reliability and validity of the Chinese version of the Oxford agoraphobic avoidance scale (OAAS-C) in Chinese college students.Methods:A total of 1 030 college students were surveyed with OAAS-C, general anxiety disorder-7(GAD-7), the center for epidemiological studies depression scale-10 (CESD-10) and the symptom checklist-90(SCL-90). Sample 1( n=30) was carried out for popularity test. Sample 2( n=503) was carried out for item analysis and exploratory factor analysis. Sample 3( n=497) was carried out for confirmatory factor analysis. Two weeks later, 60 college students who came from sample 2 were asked to retest OAAS-C. SPSS 26.0 and Mplus 8.3 were used for data analysis. Results:According to exploratory factor analysis, the OAAS-C was a single dimension scale included with 8 items, and explained 60.75% of the total variance.The confirmatory factor analysis showed that the single factor model fitted the data well( χ2/ df=1.41, CFI=0.99, TLI=0.98, RMSEA=0.05). The score of OAAS-C was positively correlated with the scores of GAD-7, CESD-10 and the agoraphobic subscale of SCL-90 ( r=0.72, 0.71, 0.87, all P<0.01). In addition, the composite reliability coefficient was 0.91 and average variance extracted coefficient was 0.55.The Cronbach's α coefficient of the OAAS-C was 0.93, the retest reliability coefficients(ICC) was 0.86, and the split-half reliability coefficient was 0.90. Conclusion:OAAS-C has a good reliability and validity in Chinese college students and it can be used as a research tool for agoraphobic study.

Objective:To explore the heterogeneity of alienation among adolescents and examine the impact of child psychological maltreatment, childhood bullying, online social exclusion, and demographic variables.Methods:In October 2023, the alienation scale was administered to 1 316 adolescents. Latent profile analysis was conducted using Mplus 8.3, and multinomial Logistic regression analysis was performed using SPSS 26.0 to explore the factors associated with the heterogeneity of adolescent alienation.Results:(1) The score of adolescent alienation was 22.00 (17.00, 29.00). The results of latent profile analysis showed that there was heterogeneity in adolescent alienation, which could be divided into two categories as low alienation (66.79%, 879/1 316) and high alienation (33.21%, 437/1 316).(2) Binary Logistic regression analysis showed that gender ( B=0.57, OR=1.77, P<0.01), being an only child ( B=-0.34, OR=0.71, P<0.05) were significantly associated with adolescent alienation. Additionally, child psychological maltreatment( B=1.61, OR=5.02, P<0.01), childhood bullying ( B=1.09, OR=2.98, P<0.01), and online social exclusion ( B=1.64, OR=5.17, P<0.01) were identified as critical factors influencing adolescent alienation. Conclusion:There is heterogeneity in alienation among adolescents. Child psychological maltreatment, child bullying, online social exclusion and demographic variables are the main influencing factors of alienation among adolescents.

Objective:To evaluate the reliability and validity of the Chinese version of the Oxford agoraphobic avoidance scale (OAAS-C) in Chinese college students.Methods:A total of 1 030 college students were surveyed with OAAS-C, general anxiety disorder-7(GAD-7), the center for epidemiological studies depression scale-10 (CESD-10) and the symptom checklist-90(SCL-90). Sample 1( n=30) was carried out for popularity test. Sample 2( n=503) was carried out for item analysis and exploratory factor analysis. Sample 3( n=497) was carried out for confirmatory factor analysis. Two weeks later, 60 college students who came from sample 2 were asked to retest OAAS-C. SPSS 26.0 and Mplus 8.3 were used for data analysis. Results:According to exploratory factor analysis, the OAAS-C was a single dimension scale included with 8 items, and explained 60.75% of the total variance.The confirmatory factor analysis showed that the single factor model fitted the data well( χ2/ df=1.41, CFI=0.99, TLI=0.98, RMSEA=0.05). The score of OAAS-C was positively correlated with the scores of GAD-7, CESD-10 and the agoraphobic subscale of SCL-90 ( r=0.72, 0.71, 0.87, all P<0.01). In addition, the composite reliability coefficient was 0.91 and average variance extracted coefficient was 0.55.The Cronbach's α coefficient of the OAAS-C was 0.93, the retest reliability coefficients(ICC) was 0.86, and the split-half reliability coefficient was 0.90. Conclusion:OAAS-C has a good reliability and validity in Chinese college students and it can be used as a research tool for agoraphobic study.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective:To investigate the prognosis and risk factors of IgA vasculitis nephritis (IgAVN) in children.Methods:A retrospective cohort study was conducted. Clinical data were collected from 264 children who were pathologically diagnosed with IgAVN at Department of Pediatric Nephrology, Tongji Hospital, affiliated with Tongji Medical College, Huazhong University of Science and Technology, between January 2011 and December 2017. All patients had a follow-up period of more than 3 years. Clinical characteristics, renal pathology, 3-year and 5-year prognosis were analyzed. The patients were grouped based on gender, age of onset (≤6 years, >6-9 years, and >9 years), pathological classification (≤Ⅲ and>Ⅲ),whether the prognosis was complete remission at 3 and 5 years. Independent sample t-tests, ANOVA or chi-squared test were used for intergroup comparisons. Spearman correlation analysis was applied for ordinal data, and multivariate Logistic regression was used to analyze factors affecting the prognosis. Receiver operating characteristic (ROC) curve was utilized to evaluate the predictive value of these factors. Results:Of the 264 children with IgAVN, 153 were male and 111 were female, the age of onset was 8.3 (6.7, 10.3) years, 118 patients (45%) with onset age >6-9 years accounted for the highest proportion. All patients presented with skin purpura and renal involvement, primarily manifesting as hematuria and/or proteinuria. Microscopic hematuria was observed in 253 patients (95.8%), while 246 patients (93.2%) showed proteinuria. In 256 patients (97.0%), hematuria or proteinuria urinalysis was detected within 6 months of skin purpura onset, and 243 patients (92.0%) underwent renal biopsy within 6 months of renal involvement. The most common clinical subtype in 264 IgAVN children was hematuria and proteinuria (204 cases, 77.3%), with grade Ⅲ being the predominant pathological classification (181 cases, 68.6%). Among children ≤6 years old, the 3-year complete remission rate was higher in males than in females (83.9% (26/31) vs. 7/16, χ2=8.12, P=0.012). Factors independently associated with poor 5-year prognosis included time from hematuria or proteinuria urinalysis to renal biopsy >6 months, elevated serum cholesterol levels, and incomplete remission 3 years post-biopsy ( OR=5.41, 1.39, 6.02, 95% CI 1.40-20.86, 1.04-1.84, 2.61-13.88, all P<0.05). The serum cholesterol has a predictive value for 5-year prognosis ( P=0.020, AUC=0.62, 95% CI 0.52-0.71, Youden index=0.27, cutoff=4.37). Conclusions:For children with IgAVN aged≤6 years, the 3-year prognosis is better in males than in females. Time from hematuria or proteinuria urinalysis to renal biopsy >6 months, elevated serum cholesterol levels, and incomplete remission at 3 years post-biopsy may be independent risk factors for poor 5-year prognosis in children with IgAVN.

Objective:To explore the risk factors and outcomes of central nervous system(CNS)complications associated with hematopoietic stem cell transplantation(HSCT).Methods:A total of 550 recipient after HSCT in the department of hematology of Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology from January 1 2019 to August 31 2021were enrolled.According to the occurrence of CNS complications, they were divided into the CNS group(24 cases)and the non CNS group(526 cases). The clinical information and prognosis were compared.We further analyzed the risk factors associated with CNS complications, and conducted multivariate logistic regression on statistically significant indicators.Cox regression analysis is conducted on prognostic factors such as age, gender and risk degree.Results:A total of 550 recipients were enrolled, of which 330 underwent allo-HSCT, and others received auto-HSCT.A total of 24 cases (4.36%)had CNS complications, of which 4 cases had 2 types of CNS complications.The type of CNS complications included intracranial infection(8 cases, 28.57%), transplantation-associated thrombotic microangiopathy(TA-TMA)(6 cases, 21.43%), central tumor invasion(4 cases, 14.29%), intracranial hemorrhage(4 cases, 14.29%), leucodystrophy(2 cases, 7.14%)and unexplained encephalopathy(4 cases, 14.29%). Logistic regression analysis of risk factors related to CNS complications showed that, Platelet implantation time( β=0.084, OR=1.088, P=0.048), CMV infection( β=1.295, OR=3.65, P=0.008)is positively correlated with the occurrence of CNS complications in HSCT recipients but age( β=-0.052, OR=0.949, P=0.004)is negatively correlated with it.Nine of the 24 cases(37.50%)who experienced CNS complications died, including 3 cases of intracranial infection, 3 cases of cerebral hemorrhage, 2 cases of TMA, and 1 case of unexplained encephalopathy.Platelet implantation time is an independent risk factor for poor prognosis of CNS complications in HSCT recipients. Conclusions:Our results indicated that, age, CMV infection and platelet implantation time were associated with the occurrence of CNS complications after HSCT.Platelet implantation time is an independent risk factor for poor prognosis of CNS complications in HSCT recipients.

Objective:To analyze the clinical characteristics, risk factors for critical illness and death of severe adenovirus pneumonia in children, so as to provide clinical evidences for early diagnosis and reliable treatment.Methods:A total of 75 pediatric cases with severe adenovirus pneumonia admitted to Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January to October 2019 were studied. The clinical features, laboratory and imaging data, therapeutic approaches, efficacy of the treatments and prognosis were investigated retrospectively. Patients were divided into severe group and critical group. Chi square test and Mann-Whitney U rank sum test were used to analyze the data of the two groups. The risk factors for critical illness and death were analyzed by univariate and multivariate Logistic regression. Results:Among the 75 children, there were 52 males and 23 females, aged from 3 months to 8 years, including 30 of severe cases and 45 of critical case. The positive rate of adenovirus antigen in nasopharyngeal swab was 21% (15/72), and the positive rate of serum adenovirus IgM antibody was only 13% (10/75). However, the positive rate of adenovirus nucleic acid in nasopharyngeal swab was 75% (21/28). What is more, the positive rates of metagenomics next generation sequencing (mNGS) in plasma and bronchoalveolar lavage fluid were 92% (33/36) and 96% (54/56), respectively, of which 95% (63/66) were confirmed as adenovirus type 7. Relatively high dose of ribavirin and integrated therapeutic approaches (respiratory support, glucocorticoids, immunoglobulin and organ supportive therapies) were used. The recovery rate was 77% (58/75), the improvement rate was 8% (6/75) and the mortality rate was 15% (11/75). The proportion of children with the duration of fever longer than 3 days after ribavirin treatment in the critical group was significantly higher than that in the severe group(51% (18/35) vs. 8% (2/26), χ 2=12.949, P<0.05). The risk factors for critical illness were younger than 4 years, longer duration of fever before and after admission to PICU, oxygenation index<300 mmHg (1 mm Hg=0.133 kPa), ferritin>1 000 μg/L, lactate dehydrogenase (LDH)>1 500 U/L, 5 lung lobes involvement, pleural effusion and (or) air leakage (all P<0.05). Among them, 5 lung lobes involvement was the independent risk factor for critical illness (adjusted OR=49.641, 95% CI 4.186-588.618, P=0.002). Risk factors for death included longer duration of fever after being admitted to PICU, oxygenation index<100 mmHg, ferritin>2 000 μg/L, interleukin (IL)-6>100 ng/L, LDH>1 500 U/L, pleural effusion and (or) air leakage (all P<0.05). Among them, IL-6>100 ng/L was the independent risk factor for the mortalities of critically ill children (adjusted OR=16.094, 95% CI2.059-25.787, P=0.008). Conclusions:The mortality rate of severe pediatric adenovirus pneumonia caused by adenovirus type 7 is high. High positive rates of adenovirus nucleic acid in nasopharyngeal swabs and mNGS in plasma or bronchoalveolar lavage fluid contribute to early diagnosis, and mNGS can also be used for serotyping. Younger children under 4 years of age, persistent fever, extensive pulmonary lesions and significantly increased inflammatory cytokines such as IL-6 are warning indicators for critical illness and poor prognosis. Relatively high dose of ribavirin combined with integrated therapeutic approaches are beneficial for prognosis.

Objective To evaluate the clinical efficacy of our self-made minimally invasive pelvic channel instrument in the treatment of pelvic ring fracture-dislocation.Methods A retrospective study was conducted of the 35 patients who had been treated for pelvic ring fracture-dislocation from December 2015 to November 2017 and fully followed up at Department I of Orthopaedis,Beijing Chaoyang Emergency Rescue Center.They were 25 males and 10 females,aged from 20 to 73 years (average,41.3 years).According to the Tile classification for pelvic fractures,there were 26 cases of type B (type B1 in 8,type B2 in 12 and type B3 in 6) and 9 cases of type C(type C1 in 5,type C2 in 3 and type C3 in 1).Infix or anterior plate combined with percutaneous internal fixation with sacroiliac cannulated screws was used in 11 patients,sacroiliac triangle fixation combined with percutaneous internal fixation with anterior ring cannulated screws in 5 ones,and internal fixation with cannulated screws for anterior and posterior rings in 19 ones.All the channels were established using our self-made minimally invasive pelvic channel instrument for internal fixation with cannulated screws.The time for each screw placement and the number of X-ray projection were recorded.Postoperative reduction,pelvic function at the final follows-ups and complications were recorded.Results A total of 84 cannulated screws were inserted in the 35 patients.The time for each cannulated screw placement ranged from 5 to 13 minutes (average,8.1 minutes);the number of X-ray projection for each screw placement ranged from 7 to 15 times (average,10.3 times).Postoperative CT showed that all the cannulated screws were located in the preset channels.According to the Matta radiological criteria,postoperative reduction quality was excellent in 29,good in 4 and fair in 2,giving a good to excellent rate of 94.3％.The follow-up time for the 35 patients ranged from 6 to 15 months (average,12.3 months).At the final follow-ups,all the patients showed fine fracture union.There was no loosening or breakage of screws in all but one patient in whom one sacroiliac screw became loose 3 months after surgery.By the Majeed criteria,the pelvic function was excellent in 27 cases,good in 5,fair in 3 and poor in one,giving a good to excellent rate of 91.4％.Conclusion Our self-made minimally invasive pelvic channel instrument can be used to establish pelvic channels,leading to more accurate placement,shorter operative time and less X-ray projection.