Objective:To compare the clinical value of digital breast tomosynthesis (DBT) localization and stereotactic positioning biopsy of breast lesions.Methods:This study was a cross-sectional study. Totally of 250 patients who underwent breast biopsy at Shenzhen People′s Hospital, Luohu District People′s Hospital and Peking University Shenzhen Hospital between August 2021 to October 2023 was analyzed retrospectively, including 136 cases of DBT-guided biopsy (DBT-guided group) and 114 cases of stereotactic-guided biopsy (stereotactic-guided group). The stereotactic-guided biopsy methods included core needle biopsy (CNB) and wire positioning. The DBT-guided biopsy methods included CNB, wire positioning and vacuum-assisted breast biopsy (VABB). The χ2 test or Mann-Whitney U test was used to compare the puncture success rate, operation time, localization time, puncture time, number of first valid localization phases obtained, number of exposures, and complications of different biopsy methods between 2 groups. Results:In the wire positioning biopy, the puncture success rate was 100% (33/33) in DBT-guided group and 96% (48/50) in the stereotactic-guided group, with no statistically significant difference between the two groups ( P=0.515). Compared to the stereotactic-guided group, the operation time and localization time were shorter, and the number of first valid localization phases obtained, number of exposures were fewer in the DBT-guided group( P<0.05). The incidence of complications was lower in both the DBT-guided group and the stereotactic-guided group, with no statistically significant difference ( P=0.871). In CNB, both the DBT-guided group and the stereotactic-guided group had higher puncture success rates, with no statistically significant difference ( P=0.080). Compared to the stereotactic-guided group, the operation time, localization time and puncture time were shorter, and the number of first valid localization phases obtained, number of exposures were lower in the DBT-guided group, and the difference between the two groups were statistically significant ( P<0.05). The incidence of complications was lower in both the DBT-guided group and the stereotactic-guided group, with no statistically significant difference ( P=0.627). Twenty-one cases received DBT-guided VABB, with an operation time of (19.90±3.38) min, a localization time of 6.00 (6.00, 7.00) min, a puncture time of (13.42±3.28) min, the number of first effective localization phases obtained was 1.00 (1.00, 1.00) time, the number of exposures was 4.00 (3.50, 5.00) times, and one case experienced severe pain after puncture. Conclusion:Compared with stereotactic-guided biopsy, DBT-guided biopsy can reduce operation time and exposure times, and can target more types of breast lesions, with higher clinical application value.

Objective: To elucidate clinical characteristics and build a prognostic nomogram for patients with vulvar cancer. Methods: The study population was drawn from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly assigned to training and validation sets. Cox proportional hazards model and competing risk model were used to identify the prognostic parameters of overall survival (OS) and cancer-specific survival (CSS) to construct a nomogram. The nomogram was assessed by concordance index (C-index), area under the curve (AUC), calibration plot, and decision curve analysis (DCA). Results: A total of 20,716 patients were included in epidemiological analysis, of whom 7,025 patients were selected in survival analysis, including 4,215 and 2,810 in training and validation sets, respectively. The multivariate Cox model showed that the predictors for OS were age, marital status, histopathology, differentiation and tumor node metastasis (TNM) stages, whether to undergo surgery and chemotherapy. However, the predictors for CSS were age, race, differentiation and TNM stages, whether to undergo surgery and radiation. The C-index for OS and CSS in the training set were 0.76 and 0.80. The AUC in the training set for 1-, 3- and 5-year OS and CSS were 0.84, 0.81, 0.80 and 0.88, 0.85, 0.83, respectively, which was similar in the validation set. The calibration curves showed good agreement between prediction and actual observations. DCA revealed that the nomogram had a better discrimination than TNM stages. Conclusions The nomogram showed accurate prognostic prediction in OS and CSS for vulvar cancer, which could provide guidance to clinical practice.

Objective:To retrospectively analyze the relationship between patterns of local recurrence and radiotherapy target dose after adjuvant radiotherapy for the pancreatic ductal adenocarcinoma(PDAC), aiming to provide reference for exploring reasonable target and dosage.Methods:Clinical data of 138 patients with T 1-4N 0-2M 0 PDAC who underwent adjuvant radiotherapy after radical resection from April 2012 to December 2020 were analyzed retrospectively. The influencing factors of local recurrence and the correlation between local recurrence site and radiotherapy target dose were analyzed. Results:The median follow-up time was 37.2 months. The median overall survival (mOS) was 29.9 months. The 5-year OS rate was 27.4%. And the median progression-free survival (mPFS) was 13.9 months. There were 24 cases of local recurrence (17.4%), and 10 cases of local recurrence complicated with distant metastasis (7.2%). The correlation between local recurrence site and radiotherapy target dose could be evaluated in 19 patients with complete clinical data. The first local recurrence occurred near the para-aortic (Ao), the celiac axis (CA) and the superior mesenteric artery (SMA) were 8, 5 and 4 cases, respectively. The radiotherapy doses of 8 patients with local recurrence only in the PTV field were above 45 Gy. There were 8 cases of local recurrence both in and out of the PTV field, including 3 cases with dose line between 40 and 52 Gy, 2 cases with dose line between 20 and 47.5 Gy, and 3 cases with dose line between 0.5 and 52.5 Gy. There were 3 cases of local recurrence out of the PTV field, and the dose line ranged from 0 to 20 Gy.Conclusions:The local recurrence rate of PDAC after radical surgery combined with postoperative radiotherapy is low, but a small number of patients have recurrence in the high-dose range of radiation field and regional recurrence out of the field. For these patients, it may be necessary to explore a more appropriate target dose and range for adjuvant radiotherapy.

Objective:To analyze clinical phenotypes and pathogenic mutations of a patient with classic tuberous sclerosis complex.Methods:Clinical data was collected from a patient with classic tuberous sclerosis complex. Next-generation sequencing was performed to screen pathogenic gene variants, and Sanger sequencing to verify the mutations. Minigene plasmids were constructed and transfected into the human renal epithelial cell line 293T, and RNA was extracted for transcriptional analysis.Results:The patient clinically presented with recurrent epileptic seizures, facial angiofibroma, periungual fibroma, pulmonary lymphangioleiomyomatosis, renal angiomyolipoma and multiple osteosclerosis. Next-generation sequencing revealed a suspected pathogenic variant in the TSC2 gene in the patient. Sanger sequencing identified a heterozygous mutation c.336_336+15delGGTAAGGCCCAGGGCG in exon 4 of the TSC2 gene in the patient, but not in his parents or 100 unrelated healthy controls. Moreover, this mutation had not been previously reported. The minigene experiment showed changed mRNA sequence of the TSC2 gene in this patient with loss of the authentic splice site in exon 4 and insertion of a 74-bp intron, which shifted the splice site 90 bp downstream (r.336delins336+16_336+90) .Conclusion:The novel heterozygous mutation c.336_336+15delGGTAAGGCCCAGGGCG in exon 4 of the TSC2 gene can lead to aberrant splicing, and may contribute to tuberous sclerosis complex in this patient.

[This corrects the article DOI: 10.1016/j.apsb.2020.05.004.].

Antibody-drug conjugates(ADCs)are commonly heterogeneous and require extensive assessment of exposure-efficacy and exposure-safety relationships in preclinical and clinical studies.In this study,we report the generation of a monoclonal antibody against monomethyl auristatin E(MMAE)and the development,validation,and application of sensitive and high-throughput enzyme-linked immunosor-bent assays(ELISA)to measure the concentrations of MMAE-conjugated ADCs and total antibodies(tAb,antibodies in ADC plus unconjugated antibodies)in cynomolgus monkey sera.These assays were suc-cessfully applied to in vitro plasma stability and pharmacokinetic(PK)studies of SMADC001,an MMAE-conjugated ADC against trophoblast cell surface antigen 2(TROP-2).The plasma stability of SMADC001 was better than that of similar ADCs coupled with PEG4-Val-Cit,Lys(m-dPEG24)-Cit,and Val-Cit linkers.The developed ELISA methods for the calibration standards of ADC and tAb revealed a correlation be-tween serum concentrations and the OD450 values,with R2 at 1.000,and the dynamic range was 0.3-35.0 ng/mL and 0.2-22.0 ng/mL,respectively;the intra-and inter-assay accuracy bias％ranged from-12.2％to-5.2％,precision ranged from-12.4％to-1.4％,and the relative standard deviation(RSD)was less than 6.6％and 8.7％,respectively.The total error was less than 20.4％.The development and validation steps of these two assays met the acceptance criteria for all addressed validation parameters,which suggested that these can be applied to quantify MMAE-conjugated ADCs,as well as in PK studies.Furthermore,these assays can be easily adopted for development of other similar immunoassays.

Tropomyosin receptor kinase A, B and C (TRKA, TRKB and TRKC), which are well-known members of the cell surface receptor tyrosine kinase (RTK) family, are encoded by the neurotrophic receptor tyrosine kinase 1, 2 and 3 (

OBJECTIVE: To explore the genetic basis for a patient diagnosed with tuberous sclerosis complex (TSC). METHODS: Peripheral blood samples of the patient and his parents were collected for the extraction of genomic DNA. Next generation sequencing (NGS) was carried out to detect potential variant, and the result was verified by Sanger sequencing. RESULTS: The patient was found to harbor a heterozygous c.1053delG (p.Glu352SerfsX10) frameshifting variant of the TSC2 gene. The same variant was not found in his unaffected parents and 100 unrelated healthy controls. Based on the American College of Medical Genetics and Genomics guidelines, the variant was predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION The novel c.1053delG (p.Glu352SerfsX10) frameshifting variant of the TSC2 gene probably underlay the TSC in this patient.
Genomics ; Heterozygote ; Humans ; Mutation ; Tuberous Sclerosis/genetics* ; Tuberous Sclerosis Complex 2 Protein/genetics*

Parkinson's disease (PD), known as one of the most universal neurodegenerative diseases, is a serious threat to the health of the elderly. The current treatment has been demonstrated to relieve symptoms, and the discovery of new small-molecule compounds has been regarded as a promising strategy. Of note, the homeostasis of the autolysosome pathway (ALP) is closely associated with PD, and impaired autophagy may cause the death of neurons and thereby accelerating the progress of PD. Thus, pharmacological targeting autophagy with small-molecule compounds has been drawn a rising attention so far. In this review, we focus on summarizing several autophagy-associated targets, such as AMPK, mTORC1, ULK1, IMPase, LRRK2, beclin-1, TFEB, GCase, ERR