Objective To analyze the proportion and clinicopathological characteristics of HER2-positive breast cancer patients with BRCA1/2 pathogenic variants, and their response to neoadjuvant anti-HER2 targeted therapy. Methods The clinicopathological data of 531 breast cancer patients with germline BRCA1/2 pathogenic variants (201 with BRCA1 variants and 330 with BRCA2 variants) were analyzed. Results Among the 201 BRCA1 and 330 BRCA2 variants, 17 (8.5%) and 42 (12.7%) HER2-positive breast cancer cases were identified, respectively, accounting for 11.1% of all BRCA1/2-mutated breast cancers. Compared with BRCA1/2-mutated HR-positive/HER2-negative patients, HER2-positive patients did not present any significant differences in clinicopathological features; however, compared with triple-negative breast cancer patients, HER2-positive patients had a later onset age and lower tumor grade. Among the 17 patients who received neoadjuvant anti-HER2 targeted therapy, 10 cases achieved pCR (58.8%), whereas 7 cases did not (41.2%). Conclusion HER2-positive breast cancer accounts for more than 10% of BRCA1/2-mutated patients. Approximately 40% of these patients fail to achieve pCR after neoadjuvant targeted therapy. This phenomenon highlights the possibility of combining anti-HER2 targeted agents with poly (adenosine diphosphate-ribose) polymerase inhibitors.

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

OBJECTIVE To systematically evaluate the incidence of anti-tuberculosis drug-induced liver injury （ATB-DILI） and its risk factors. METHODS PubMed， Embase， the Cochrane Library， Web of Science， China Knowledge Network， VIP， Wanfang data and China Biomedical Literature Database were searched to collect cohort studies and case-control studies on the incidence and risk factors of ATB-DILI from the establishment of the database to 31 May 2024. After screening literature， extracting data and evaluating the quality of literature， meta-analysis was performed using Stata 17.0 and RevMan 5.3 software. RESULTS A total of 26 literature involving 38 971 patients were included， of which 4 106 patients suffered from ATB-DILI. Meta-analysis showed that the incidence of ATB-DILI was 12.94% [95%CI （10.82%，15.06%）， P＜0.001]； subgroup analysis showed that the incidence of ATB-DILI in cohort studies， Chinese studies and pediatric patients was higher （P＜0.001）. Age≥60 years， abnormal body mass index， alcoholism， smoking， history of liver disease， hepatitis B surface antigen positivity， extrapulmonary tuberculosis， malnutrition， hypoproteinemia， cardiovascular disease， diabetes mellitus， systemic lupus erythematosus， no prophylactic use of hepatoprotective drugs， and high baseline alanine transaminase levels were risk factors for developing ATB-DILI （P＜0.05）. Sensitivity analysis and publication bias analysis showed that the results obtained in this study were relatively robust. CONCLUSIONS The incidence of ATB-DILI in tuberculosis patients is 12.94%. Age≥60 years， abnormal body mass index， alcoholism， smoking， history of liver disease， hepatitis B surface antigen positivity， extrapulmonary tuberculosis， malnutrition， hypoproteinaemia， cardiovascular disease， diabetes mellitus， systemic lupus erythematosus， non-prophylactic use of hepatoprotective medications， and high baseline levels of alanine transaminase are the risk factors for developing ATB-DILI.

Objective To investigate the potential significance of FOXP3 expression in BRCA1/2-mutant breast cancer.Methods A total of 48 BRCA mutation carriers(16 with BRCA1 and 32 with BRCA2)and 78 age-matched non-carriers were included in this study.Immunohistochemistry was used to detect the expression of FOXP3 in breast cancer tissues.The FOXP3 RNA expression in 39 BRCA1,36 BRCA2,and 948 non-carrier breast cancer patients from TCGA-BRCA and the correlation with homologous recombin-ation deficiency scores were evaluated to validate the immunohistochemistry results.Results The FOXP3 positive rate was 43.8%(7/16)in BRCA1 mutation carriers,59.4%(19/32)in BRCA2 mutation carriers,and 9.0%(7/78)in non-carriers.The FOXP3 positive rates in patients with BRCA1/2 mutant breast cancer were significantly higher than those in non-carriers(P=0.002;P<0.001).TCGA-BRCA results showed that the FOXP3 RNA level in BRCA1/2 mutant breast cancer was significantly higher than that in non-carriers(P=0.02,P=0.004).The FOXP3 RNA level was positively correlated with the homologous recombination deficiency score(Spearman R=0.30,P<2.2e-16).Conclusion Patients with BRCA1/2 mutant breast cancers have higher FOXP3expression than non-carriers,and may be more sensitive to immunotherapy.

Glioma is the most common primary tumor of the brain,accounting for 81%of central nervous system(CNS)malignant tumors.The degree of malignancy is high,and the current treatment methods are limited.In recent years,with the in-depth study of intestinal flora and brain-gut axis,it has been found that the diversity of gut microbiota plays an important role in the regulation of glioma.The mechanism is that the intestinal flora affects the development of glioma through the role of immune regulation and metabolites.In addition,it has been con-firmed that there is a certain correlation between some probiotics and glioma,which provides a new application prospect for the treatment of glioma.This paper discusses the main intestinal bacteria that regulate gliomas as well as the role and regulatory mechanisms of intestinal flora in the development of gliomas,and provides ideas for the discovery of new targets for glioma treatment and further improvement of treatment options.

Objective:To summarize long-term clinical follow-up results of segment instability between the upper instrumented vertebra (UIV) and the adjacent upper vertebra (UIV+1) and to establish the optimal timing for surgery for UIV+1.Methods:A retrospective analysis was conducted on 265 patients with lumbar degenerative diseases who underwent transforaminal lumbar interbody fusion (TLIF) surgery at the Department of Spinal Surgery, Zhongda Hospital, from January 2014 to December 2018. The cohort included 119 male and 146 female patients, with an average age of 64.93 years (range: 32-86 years). Preoperative dynamic imaging measured sagittal angulation (SA) and sagittal translation (ST) of the UIV+1/UIV segment. Patients with SA>10° or ST>2 mm were categorized into the unstable group, further divided into the unstable non-fusion group and the unstable fusion group based on whether UIV+1 expansion fusion was performed. The remaining patients were classified into the stable group. Imaging indicators, Visual Analogue Scale (VAS) scores, Oswestry disability index (ODI) scores, and Japanese Orthopaedic Association (JOA) scores were compared among the groups, with JOA improvement rates calculated to assess clinical efficacy. Pearson correlation coefficient analysis was employed to examine correlations between preoperative imaging indicators and final follow-up JOA improvement rates. Receiver Operating Characteristic (ROC) curves and the maximum Youden index were utilized to determine thresholds for preoperative SA and ST.Results:The follow-up duration for all patients was 73.53±12.92 months (range: 61-108 months). The stable group (124 cases) included 61 males and 63 females, aged 64.31±9.83 years (range: 44-82 years). The unstable non-fusion group (59 cases) included 22 males and 37 females, aged 65.76±11.01 years (range: 32-86 years). The unstable fusion group (82 cases) included 36 males and 46 females, aged 65.26±8.68 years (range: 47-80 years). At the last follow-up, the unstable non-fusion group exhibited ΔSA 0.90°±1.97° and ΔST 0.77±1.27 mm, both significantly higher than the stable group's ΔSA 0.25°±1.57° and ΔST 0.34±0.34 mm ( t=3.564, P<0.001; t=2.311, P=0.022). Clinical improvements were lower in the unstable non-fusion group compared to the other two groups: VAS (2.28±0.83), ODI (5.91%±3.46%), JOA (24.11±1.78), with a JOA improvement rate of 60%. The stable group showed VAS (1.51±0.69), ODI (3.71%±1.75%), JOA (27.33±1.91), with a JOA improvement rate of 83%. The unstable fusion group had VAS (1.46±0.83), ODI (3.46%±1.81%), JOA (26.48±1.66), with a JOA improvement rate of 78%. These differences were statistically significant ( F=32.117, P<0.001; F=24.827, P<0.001; F=92.658, P<0.001; F=93.341, P<0.001). The JOA improvement rate was negatively correlated with preoperative SA ( r=-0.363, P<0.001) to a low extent, and with preoperative ST ( r=-0.596, P<0.001) to a moderate extent. ROC curve analysis determined the preoperative SA threshold as 11.5° and the preoperative ST threshold as 1.85 mm. Conclusion:Pre-existing instability of the responsible segment UIV and UIV+1 (SA>10° or ST>2 mm) may worsen during long-term follow-up after TLIF. When preoperative SA exceeds 11.5° and ST exceeds 1.85 mm between UIV and UIV+1, performing an extended fusion involving UIV+1 can ensure surgical efficacy over long-term follow-up.

Objective To compare the clinicopathological characteristics between primary and contralateral cancers in patients with metachronous bilateral breast cancer (MBBC) who carried a BRCA1/2 germline pathogenic variant. Methods A total of 496 BRCA1/2 carriers with primary unilateral breast cancer were included (196 with BRCA1 and 300 with BRCA2). Clinicopathological information of patients was collected, and the median follow-up for the entire cohort was 10.4 years (0.4-20.8 years). Results Among all patients, 31 (15.8%) of the 196 BRCA1 carriers and 49 (16.3%) of the 300 BRCA2 carriers had MBBC, respectively. Among the 31 BRCA1 carriers who developed MBBC, the proportion of triple-negative breast cancer (TNBC) in primary cancer and contralateral cancer was 61.3% and 67.7%, respectively. If the primary cancer of BRCA1-mutated MBBC was TNBC, the probability of the contralateral breast cancer with TNBC was 89.5% (17/19), which was significantly higher than that if the primary cancer was non-TNBC (33.3%, 4/12) (P=0.004). Among the 49 BRCA2 carriers who developed MBBC, the predominant molecular phenotype of the primary and contralateral cancers was HR+ & HER2- (77.6% and 67.3%, respectively; P=0.53). Conclusion Approximately 60% of BRCA1 carriers exhibit TNBC. If a BRCA1 carrier with a TNBC primary breast cancer had an MBBC, the probability of the contralateral breast cancer being TNBC phenotype is almost 89.5%.

Humans ; Pregnancy ; Female ; Umbilical Cord/diagnostic imaging* ; Pregnancy Outcome ; Ultrasonography ; Ultrasonography, Prenatal

Objective:To examine the difference of long-term recurrence rate and survivals between the young patients and the old patients undergoing breast conserving therapy (BCT).Methods:Women with primary invasive breast cancer receiving BCT between December 1999 and December 2014 were selected retrospectively from the database of Breast Cancer Center, Peking University Cancer Hospital & Institute. The median age of all patients was 47 years (range: 21 to 91 years). The cases were categorized according to age at diagnosis into two subgroups: the ≤40 years group and the>40 years group. A total of 2 778 patients were included: 677 patients in the ≤40 years group and 2 101 patients in the >40 years group. Clinicopathological characteristics between two groups were compared. The recurrence rate and survival were calculated using the Kaplan-Meier method. The differences of outcomes were compared in different aged groups using the Log-rank test. Factors affecting local recurrence, distant disease-free survival (DDFS), disease-free survival (DFS), and breast cancer-specific survival (BCSS) were assessed by multivariable Cox proportional hazard models.Results:Proportions of T1 (301/677 vs. 1 160/2 101, χ2=37.660, P<0.01), involved lymph node (314/677 vs. 713/2 101, χ2=34.966, P<0.01) hormone receptor-negative (490/677 vs. 1 581/2 101, χ2=6.981, P=0.030) and neoadjuvant chemotherapy (413/677 vs. 1 010/2 101, χ 2=34.272, P<0.01)in the ≤40 years group were higher than that in the>40 years group. Median follow-up duration was 102 months. No significant difference in 10-year local recurrence was found between the two groups (2.5% vs. 1.6%, P=0.147). Ten-year DDFS rate in the ≤40 years group and in the>40 years group was 90.6% and 95.3%, respectively ( P<0.01). Ten-year DFS rate in the ≤40 years group and in the>40 years group was 86.5% and 91.1%, respectively ( P=0.001). Ten-year BCSS rate in the ≤40 years group and in the >40 years group was 91.0% and 93.7%, respectively ( P=0.105). Age was not the prognosis factor of local recurrence. Lymph node status (positive vs. negative: HR=2.73, 95%CI: 1.94 to 3.84, P<0.01), age (≤40 years vs.>40 years: HR=1.73, 95%CI: 1.24 to 2.42, P=0.001) and T stage (>2 cm vs. ≤2 cm: HR=1.61, 95%CI: 1.14 to 2.28, P=0.001) were the prognosis factors of DDFS, and also for DFS. Hormone receptor status (positive vs. negative: HR=0.54, 95%CI: 0.39 to 0.74, P<0.01), lymph node status (positive vs. negative: HR=2.94, 95%CI: 2.12 to 4.07, P<0.01) and T stage (>2 cm vs. ≤2 cm: HR=1.45, 95%CI: 1.05 to 2.01, P=0.025) were the prognosis factors of BCSS. Conclusions:The risk of local recurrence was similar between ≤40 years patient and >40 years patients receiving breast conserving therapy. Worse survivals in the ≤40 years group were found comparing to those in the >40 years group.

Objective:To examine the difference of long-term recurrence rate and survivals between the young patients and the old patients undergoing breast conserving therapy (BCT).Methods:Women with primary invasive breast cancer receiving BCT between December 1999 and December 2014 were selected retrospectively from the database of Breast Cancer Center, Peking University Cancer Hospital & Institute. The median age of all patients was 47 years (range: 21 to 91 years). The cases were categorized according to age at diagnosis into two subgroups: the ≤40 years group and the>40 years group. A total of 2 778 patients were included: 677 patients in the ≤40 years group and 2 101 patients in the >40 years group. Clinicopathological characteristics between two groups were compared. The recurrence rate and survival were calculated using the Kaplan-Meier method. The differences of outcomes were compared in different aged groups using the Log-rank test. Factors affecting local recurrence, distant disease-free survival (DDFS), disease-free survival (DFS), and breast cancer-specific survival (BCSS) were assessed by multivariable Cox proportional hazard models.Results:Proportions of T1 (301/677 vs. 1 160/2 101, χ2=37.660, P<0.01), involved lymph node (314/677 vs. 713/2 101, χ2=34.966, P<0.01) hormone receptor-negative (490/677 vs. 1 581/2 101, χ2=6.981, P=0.030) and neoadjuvant chemotherapy (413/677 vs. 1 010/2 101, χ 2=34.272, P<0.01)in the ≤40 years group were higher than that in the>40 years group. Median follow-up duration was 102 months. No significant difference in 10-year local recurrence was found between the two groups (2.5% vs. 1.6%, P=0.147). Ten-year DDFS rate in the ≤40 years group and in the>40 years group was 90.6% and 95.3%, respectively ( P<0.01). Ten-year DFS rate in the ≤40 years group and in the>40 years group was 86.5% and 91.1%, respectively ( P=0.001). Ten-year BCSS rate in the ≤40 years group and in the >40 years group was 91.0% and 93.7%, respectively ( P=0.105). Age was not the prognosis factor of local recurrence. Lymph node status (positive vs. negative: HR=2.73, 95%CI: 1.94 to 3.84, P<0.01), age (≤40 years vs.>40 years: HR=1.73, 95%CI: 1.24 to 2.42, P=0.001) and T stage (>2 cm vs. ≤2 cm: HR=1.61, 95%CI: 1.14 to 2.28, P=0.001) were the prognosis factors of DDFS, and also for DFS. Hormone receptor status (positive vs. negative: HR=0.54, 95%CI: 0.39 to 0.74, P<0.01), lymph node status (positive vs. negative: HR=2.94, 95%CI: 2.12 to 4.07, P<0.01) and T stage (>2 cm vs. ≤2 cm: HR=1.45, 95%CI: 1.05 to 2.01, P=0.025) were the prognosis factors of BCSS. Conclusions:The risk of local recurrence was similar between ≤40 years patient and >40 years patients receiving breast conserving therapy. Worse survivals in the ≤40 years group were found comparing to those in the >40 years group.