Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.

Objectives:To evaluate the clinical value of the Paris system for reporting urinary cytology (TPS) in the diagnosis of urothelial carcinoma (UC).Methods:A total of 1 744 cytological diagnostic records (from 751 cases) were collected retrospectively. All specimens were voided urines and histopathology as the gold standard. The sensitivity and specificity of urinary cytological diagnosis of UC and risk of high grade malignant (ROHM) in each diagnostic category were compared.Results:There were 360 cases with histopathology. The percentage of negative for high-grade urothelial carcinoma (NHGUC) was 30.1% (226/751), atypical urothelial cells (AUC) was 29.8% (224/751), suspicious for high-grade urothelial carcinoma (SHGUC) was 16.8% (126/751), high grade urothelial carcinoma (HGUC) was 21.2% (159/751), and non-urothelial malignancy (NUM) was 2.1% (16/751). The histpathologic ROHM corresponding to each cytological diagnosis category were 27.3% for NHGUC, 32.7% for AUC, 74.7% for SHGUC, 96.6% for HGUC and 100.0% for NUM, respectively. ROHM of SHGUC was significantly higher than that of AUC group, and the difference between the two groups was statistically significant ( P＜0.001). ROHM of HGUC group was significantly higher than that of SHGUC group, and the difference was statistically significant ( P＜0.001). With SHGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 76.7% (165/215) and 85.7% (18/21), and with HGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 53.0% (114/215) and 100.0% (21/21), respectively. Conclusions:Urine cytology has high sensitivity and specificity in the diagnosis of HGUC. The malignant risk of TPS varies with different diagnosis category. The high malignant risk population in cancer hospital leads to the relatively high malignant proportion and ROHM in each diagnosis category. Urinary cytology TPS reporting system is helpful to clinical management and has good clinical application value.

Objective:To evaluate the utility of the 9-gene panel as a differential diagnostic method for thyroid nodules within determinate cytological diagnosis and as a parallel diagnostic method for thyroid fine-needle aspiration (FNA) cytology.Methods:579 liquid-based cytology samples from 544 patients were collected after thyroid FNA diagnosis in our hospital from December 2014 to April 2021. Mutations at any site of 9 genes, namely, BRAF, NRAS, HRAS, KRAS, GNAS, RET, TERT, TP53, and PIK3CA as recorded by the Catalogue of Somatic Mutations in Cancer (COSMIC), were analyzed by next-generation sequencing. Taking postoperative histopathology and cytology results with definite benign or malignant diagnosis as the gold standard, the diagnostic efficacy of the 9-gene panel as a reclassified method for thyroid nodules with indeterminate cytological diagnosis and as a parallel diagnostic method for thyroid FNA cytology were evaluated and compared with that of the BRAF V600E single-gene detection method.Results:Of the 579 thyroid nodules, 196 (33.85%) were Bethesda Ⅱ, 11 (1.90%) were Bethesda Ⅲ, 31 (5.35%) were Bethesda Ⅳ, 27 (4.66%) were Bethesda Ⅴ, and 314 (54.23%) were Bethesda Ⅵ, as diagnosed by thyroid FNA cytology. Among these 579 thyroid nodules, 275 were tested positive for 9-gene mutations, with a mutation rate of 47.5%. Of the 329 thyroid nodules surgically removed, 30 (9.12%) were benign, 5 (1.52%) were borderline, and 294 (89.36%) were malignant. Regarding borderline nodules as malignant nodules, the mutation rates of the 9 genes in the 299 malignant thyroid nodules from high to low were BRAF 62.21% (186/299), NRAS 5.02% (15/299), HRAS 1.00% (3/299), PIK3CA 0.67% (2/299), GNAS 0.67% (2/299), KRAS 0.33% (1/299), TP53 0.33% (1/299), TERT 0.33% (1/299) and RET 0.00% (0/299). The malignant risks of the 9 genes from high to low were BRAF 100% (186/186), PIK3CA 100.00% (2/2), GNAS 100.00% (2/2), TERT 100.00% (1/1), TP53 100.00% (1/1), NRAS 78.95% (15/19), HRAS 75.00% (3/4), and KRAS 50.00% (1/2). For thyroid nodules of Bethesda Ⅲ-Ⅳ (indeterminate diagnosis), the sensitivity (SN) of the 9-gene panel in diagnosing thyroid cancer is 34.48% (10/29), the specificity (SP) is 61.54% (8/13), and the accuracy is 42.86% (18/42); whereas the SN of the BRAF V600E detection method is 0%. Therefore, the diagnostic efficiency of the 9-gene panel is significantly better than that of BRAF V600E single gene detection. For thyroid nodules of Bethesda Ⅱ-Ⅵ, the SN of the 9-gene panel in diagnosing thyroid cancer was 68.83% (254/369), the SP was 90.00% (189/210), the accuracy was 76.51% (443/579), and the area under the curve (AUC) was 0.79; whereas the SN of BRAF V600E single-gene detection in diagnosing thyroid cancer was 63.69% (235/369), the SP was 99.52% (209/210), the accuracy was 76.68% (444/579), and the AUC was 0.82. The SP of BRAF V600E detection is higher than that of the 9-gene panel ( P＜0.01), but there is no significant difference in SN, accuracy (both P＞0.05), and AUC ( Z=0.85, P=0.396) between them. Gene mutations indicating poor prognosis were detected in 4 nodules of papillary thyroid carcinoma and 1 nodules of follicular thyroid carcinoma, including 2 nodules with TERT and BRAF V600E co-mutations, 1 nodule with TP53 mutation, and 2 nodules with PIK3CA mutation. Conclusions:As a reclassified method for thyroid lesions with indeterminate cytological diagnosis, the 9-gene panel is better than BRAF V600E single gene detection. As a parallel diagnostic method of thyroid FNA cytology, the 9-gene panel has similar diagnostic efficacy as BRAF V600E single-gene detection. The 9-gene panel can detect individual cases with gene mutations indicating poor prognosis. The identification of patients with these special gene mutations has certain implications for the clinical management of them.

Objectives:To evaluate the clinical value of the Paris system for reporting urinary cytology (TPS) in the diagnosis of urothelial carcinoma (UC).Methods:A total of 1 744 cytological diagnostic records (from 751 cases) were collected retrospectively. All specimens were voided urines and histopathology as the gold standard. The sensitivity and specificity of urinary cytological diagnosis of UC and risk of high grade malignant (ROHM) in each diagnostic category were compared.Results:There were 360 cases with histopathology. The percentage of negative for high-grade urothelial carcinoma (NHGUC) was 30.1% (226/751), atypical urothelial cells (AUC) was 29.8% (224/751), suspicious for high-grade urothelial carcinoma (SHGUC) was 16.8% (126/751), high grade urothelial carcinoma (HGUC) was 21.2% (159/751), and non-urothelial malignancy (NUM) was 2.1% (16/751). The histpathologic ROHM corresponding to each cytological diagnosis category were 27.3% for NHGUC, 32.7% for AUC, 74.7% for SHGUC, 96.6% for HGUC and 100.0% for NUM, respectively. ROHM of SHGUC was significantly higher than that of AUC group, and the difference between the two groups was statistically significant ( P＜0.001). ROHM of HGUC group was significantly higher than that of SHGUC group, and the difference was statistically significant ( P＜0.001). With SHGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 76.7% (165/215) and 85.7% (18/21), and with HGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 53.0% (114/215) and 100.0% (21/21), respectively. Conclusions:Urine cytology has high sensitivity and specificity in the diagnosis of HGUC. The malignant risk of TPS varies with different diagnosis category. The high malignant risk population in cancer hospital leads to the relatively high malignant proportion and ROHM in each diagnosis category. Urinary cytology TPS reporting system is helpful to clinical management and has good clinical application value.

Objective:To evaluate the utility of the 9-gene panel as a differential diagnostic method for thyroid nodules within determinate cytological diagnosis and as a parallel diagnostic method for thyroid fine-needle aspiration (FNA) cytology.Methods:579 liquid-based cytology samples from 544 patients were collected after thyroid FNA diagnosis in our hospital from December 2014 to April 2021. Mutations at any site of 9 genes, namely, BRAF, NRAS, HRAS, KRAS, GNAS, RET, TERT, TP53, and PIK3CA as recorded by the Catalogue of Somatic Mutations in Cancer (COSMIC), were analyzed by next-generation sequencing. Taking postoperative histopathology and cytology results with definite benign or malignant diagnosis as the gold standard, the diagnostic efficacy of the 9-gene panel as a reclassified method for thyroid nodules with indeterminate cytological diagnosis and as a parallel diagnostic method for thyroid FNA cytology were evaluated and compared with that of the BRAF V600E single-gene detection method.Results:Of the 579 thyroid nodules, 196 (33.85%) were Bethesda Ⅱ, 11 (1.90%) were Bethesda Ⅲ, 31 (5.35%) were Bethesda Ⅳ, 27 (4.66%) were Bethesda Ⅴ, and 314 (54.23%) were Bethesda Ⅵ, as diagnosed by thyroid FNA cytology. Among these 579 thyroid nodules, 275 were tested positive for 9-gene mutations, with a mutation rate of 47.5%. Of the 329 thyroid nodules surgically removed, 30 (9.12%) were benign, 5 (1.52%) were borderline, and 294 (89.36%) were malignant. Regarding borderline nodules as malignant nodules, the mutation rates of the 9 genes in the 299 malignant thyroid nodules from high to low were BRAF 62.21% (186/299), NRAS 5.02% (15/299), HRAS 1.00% (3/299), PIK3CA 0.67% (2/299), GNAS 0.67% (2/299), KRAS 0.33% (1/299), TP53 0.33% (1/299), TERT 0.33% (1/299) and RET 0.00% (0/299). The malignant risks of the 9 genes from high to low were BRAF 100% (186/186), PIK3CA 100.00% (2/2), GNAS 100.00% (2/2), TERT 100.00% (1/1), TP53 100.00% (1/1), NRAS 78.95% (15/19), HRAS 75.00% (3/4), and KRAS 50.00% (1/2). For thyroid nodules of Bethesda Ⅲ-Ⅳ (indeterminate diagnosis), the sensitivity (SN) of the 9-gene panel in diagnosing thyroid cancer is 34.48% (10/29), the specificity (SP) is 61.54% (8/13), and the accuracy is 42.86% (18/42); whereas the SN of the BRAF V600E detection method is 0%. Therefore, the diagnostic efficiency of the 9-gene panel is significantly better than that of BRAF V600E single gene detection. For thyroid nodules of Bethesda Ⅱ-Ⅵ, the SN of the 9-gene panel in diagnosing thyroid cancer was 68.83% (254/369), the SP was 90.00% (189/210), the accuracy was 76.51% (443/579), and the area under the curve (AUC) was 0.79; whereas the SN of BRAF V600E single-gene detection in diagnosing thyroid cancer was 63.69% (235/369), the SP was 99.52% (209/210), the accuracy was 76.68% (444/579), and the AUC was 0.82. The SP of BRAF V600E detection is higher than that of the 9-gene panel ( P＜0.01), but there is no significant difference in SN, accuracy (both P＞0.05), and AUC ( Z=0.85, P=0.396) between them. Gene mutations indicating poor prognosis were detected in 4 nodules of papillary thyroid carcinoma and 1 nodules of follicular thyroid carcinoma, including 2 nodules with TERT and BRAF V600E co-mutations, 1 nodule with TP53 mutation, and 2 nodules with PIK3CA mutation. Conclusions:As a reclassified method for thyroid lesions with indeterminate cytological diagnosis, the 9-gene panel is better than BRAF V600E single gene detection. As a parallel diagnostic method of thyroid FNA cytology, the 9-gene panel has similar diagnostic efficacy as BRAF V600E single-gene detection. The 9-gene panel can detect individual cases with gene mutations indicating poor prognosis. The identification of patients with these special gene mutations has certain implications for the clinical management of them.

Humans ; East Asian People ; Nausea/drug therapy* ; Vomiting/drug therapy* ; Antineoplastic Agents/adverse effects* ; Neoplasms/drug therapy*

Objective:To investigate the molecular testing of liquid-based cytology (LBC) specimens from advanced non-small cell lung cancer (NSCLC) patients and the reliability of guiding targeted therapy.Methods:The LBC specimens and clinical data of 412 advanced NSCLC patients from March 2015 to April 2017 in the Cancer Hospital, Chinese Academy of Medical Sciences were collected, of which 32 patients had postoperative or biopsy specimens. The real-time quantitative polymerase chain reaction was used to detect mutations of EGFR, KRAS and BRAF, and analyze the correlation between gene mutations and clinicopathological characteristics. The results of genetic testing of LBC specimens and histology specimens were examined for concordance. Clinical efficacy was evaluated in 142 patients treated with EGFR-tyrosine kinase inhibitor (TKI) drugs, and survival analysis was performed using the Kaplan-Meier method.Results:Of the 412 LBC specimens, 216 (52.4%) had EGFR mutations, 36 (8.7%) had KRAS gene mutations, and 3 (0.7%) had BRAF gene mutations. EGFR mutation was associated with gender, pathology type, and specimen source, with a higher EGFR mutation rate in female patients (63.0%) than in male patients (40.8%, P<0.001) and a higher EGFR mutation rate in adenocarcinoma (54.3%) than in non-adenocarcinoma (0.0%, P<0.001). KRAS mutation was related to gender, with a higher EGFR mutation rate in male patients (12.2%) than in female patients (5.6%, P=0.016). The three cases with multiple co-mutations were all stage Ⅳ male adenocarcinoma patients. Thirty-two patients with both LBC specimens and histology specimens had concordant genetic results between LBC specimens and histology specimens in 30 patients ( Kappa=0.91). Twelve patients with both histology and LBC specimens from metastases had identical genetic results ( Kappa=1.00). Nineteen patients with histology specimens from primary foci in lungs and LBC specimens from metastases had concordant genetic results between two specimens in 18 patients ( Kappa=0.92). The disease control rate (DCR) for EGFR mutation-positive patients treated with EGFR-TKI was 89.0% (89/100) and the progression-free survival time (PFS) was 13.8 months, both higher than those of EGFR mutation-negative patients [DCR of 30.8% (4/13) and median PFS of 1.4 months, P<0.01]. Conclusions:The results of molecular testing of LBC specimens and histological specimens are highly consistent, which demonstrates LBC specimens can be a crucial source of gene testing for advanced NSCLC. Molecular typing of advanced NSCLC based on the results of genetic testing of LBC specimens and guiding EGFR-TKI drug-targeted therapy can achieve high DCR and PFS, which has important clinical value.

Objective:To investigate the molecular testing of liquid-based cytology (LBC) specimens from advanced non-small cell lung cancer (NSCLC) patients and the reliability of guiding targeted therapy.Methods:The LBC specimens and clinical data of 412 advanced NSCLC patients from March 2015 to April 2017 in the Cancer Hospital, Chinese Academy of Medical Sciences were collected, of which 32 patients had postoperative or biopsy specimens. The real-time quantitative polymerase chain reaction was used to detect mutations of EGFR, KRAS and BRAF, and analyze the correlation between gene mutations and clinicopathological characteristics. The results of genetic testing of LBC specimens and histology specimens were examined for concordance. Clinical efficacy was evaluated in 142 patients treated with EGFR-tyrosine kinase inhibitor (TKI) drugs, and survival analysis was performed using the Kaplan-Meier method.Results:Of the 412 LBC specimens, 216 (52.4%) had EGFR mutations, 36 (8.7%) had KRAS gene mutations, and 3 (0.7%) had BRAF gene mutations. EGFR mutation was associated with gender, pathology type, and specimen source, with a higher EGFR mutation rate in female patients (63.0%) than in male patients (40.8%, P<0.001) and a higher EGFR mutation rate in adenocarcinoma (54.3%) than in non-adenocarcinoma (0.0%, P<0.001). KRAS mutation was related to gender, with a higher EGFR mutation rate in male patients (12.2%) than in female patients (5.6%, P=0.016). The three cases with multiple co-mutations were all stage Ⅳ male adenocarcinoma patients. Thirty-two patients with both LBC specimens and histology specimens had concordant genetic results between LBC specimens and histology specimens in 30 patients ( Kappa=0.91). Twelve patients with both histology and LBC specimens from metastases had identical genetic results ( Kappa=1.00). Nineteen patients with histology specimens from primary foci in lungs and LBC specimens from metastases had concordant genetic results between two specimens in 18 patients ( Kappa=0.92). The disease control rate (DCR) for EGFR mutation-positive patients treated with EGFR-TKI was 89.0% (89/100) and the progression-free survival time (PFS) was 13.8 months, both higher than those of EGFR mutation-negative patients [DCR of 30.8% (4/13) and median PFS of 1.4 months, P<0.01]. Conclusions:The results of molecular testing of LBC specimens and histological specimens are highly consistent, which demonstrates LBC specimens can be a crucial source of gene testing for advanced NSCLC. Molecular typing of advanced NSCLC based on the results of genetic testing of LBC specimens and guiding EGFR-TKI drug-targeted therapy can achieve high DCR and PFS, which has important clinical value.

Objective:To compare the diagnostic values of C-TIRADS, ACR-TIRADS and EU-TIRADS.Methods:According to the classification methods of the 3 guidelines, the ultrasonographic features of 283 thyroid nodules from 266 patients in Sir Run Run Shaw Hospital from January 2019 to June 2020 were analyzed retrospectively. The pathological results were taken as the gold standard, the malignant percentage of different classification was calculated, the ROC curve was plotted, the area under the ROC curve (AUC) and the best diagnostic cut-off value were calculated, and the diagnostic values of the three guidelines were compared. According to the FNA recommendations of the guidelines, the recommended number of thyroid nodules and the detection rate of malignant nodules in different guidelines were analyzed.Results:The AUCs of C-TIRADS, ACR-TIRADS and EU-TIRADS were 0.80, 0.66, 0.61, respectively. The AUC of C-TIRADS was higher than those of ACR-TIRADS and EU-TIRADS ( P<0.001, P<0.001). The best diagnostic cutoff values of C-TIRADS, ACR-TIRADS and EU-TIRADS were 4C, 5 and 5, respectively. Under the critical points, the sensitivities of the 3 guidelines were 95.27%, 98.10%, 99.53%, the specificities were 54.17%, 33.33%, 20.83%, respectively. There was no significant difference in the number of FNA recommendations among the 3 guidelines(all P>0.05), their FNA recommendations were highly consistent (Kappa>0.9). Conclusions:The diagnostic value of C-TIRADS in the classification of benign and malignant thyroid nodules is higher than those of ACR-TIRADS and EU-TIRADS. The best critical value for diagnosis of thyroid nodules is C-TIRADS 4C. The three guidelines are similar in the number of FNA recommendations and the detection rate of malignancy.

The rapid development of point-of-care testing (POCT) in clinical laboratories has brought challenges to the unified management in the hospital. There are many problems, such as how to ensure the ability and qualification of POCT operators, how to improve the quality management awareness of human, machines, materials, methods and environment in the process of POCT in clinical laboratories, how to help the clinical laboratories in the hospital to carry out POCT comparison, and how to strengthen the information construction of POCT in the hospital. Thus, this article reviews the practice and experience of POCT management in our hospital on POCT quality assurance and the problems existing in POCT in clinical departments, proposes suggestions and solutions to strengthen the unified management of POCT in clinical laboratories and establish POCT quality management documents and to improve quality awareness. We hope to provide references for hospital administrators, medical departments, nursing departments, quality control departments and other functional departments on the quality management of POCT in the hospital, and find helpful answers to the puzzles of clinical laboratory in POCT, so as to make joint efforts to standardize the quality management of POCT in the hospital to ensure the accuracy of testing results.