The dual induction therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has resulted in a cure rate exceeding 90% for patients with acute promyelocytic leukemia (APL). However, relapse due to ATO resistance remains a pressing clinical challenge. This article reviews recent research progress of PML mutations, metabolic adaptation, ATO metabolism, miRNA, snoRNA, the pathogenic mechanisms of the PML::RARA fusion protein and resistance mechanisms of autophagy. Additionally, the paper also discusses the clinical application of new treatment strategies such as venetoclax and gemtuzumab ozogamicin based on the drug-resistance mechanisms.

Drug-induced liver injury(DILI),induced by drugs and/or their reactive metabolites,is a common and challenging clinical issue.Bile acid profiles reflect both the species and contents of biolog-ical bile acids,and the perturbation of bile acid homeostasis is considered one of the early pathogene-sis events in DILI.This review summarizes the synthesis,transport and regulation of bile acids,the roles of bile acids in early warning,the relationships between different bile acids,clinical prognosis of DILI,and the potential therapeutic targets for DILI in the bile acid metabolic pathway,such as the path-ways based on the farnesoid X receptor(FXR)and G-protein coupled bile acid receptor 1(GPBAR1),as well as the balance of the gut microbiota.This study is expected to provide data for the application of bile acid metabolism in the early diagnosis,prediction,and clinical treatment of DILI.

Drug-induced liver injury(DILI),induced by drugs and/or their reactive metabolites,is a common and challenging clinical issue.Bile acid profiles reflect both the species and contents of biolog-ical bile acids,and the perturbation of bile acid homeostasis is considered one of the early pathogene-sis events in DILI.This review summarizes the synthesis,transport and regulation of bile acids,the roles of bile acids in early warning,the relationships between different bile acids,clinical prognosis of DILI,and the potential therapeutic targets for DILI in the bile acid metabolic pathway,such as the path-ways based on the farnesoid X receptor(FXR)and G-protein coupled bile acid receptor 1(GPBAR1),as well as the balance of the gut microbiota.This study is expected to provide data for the application of bile acid metabolism in the early diagnosis,prediction,and clinical treatment of DILI.

Objective:To explore the prognostic value of BRCA1-associated protein 1 (BAP1) expression loss in patients with malignant mesothelioma (MM) .Methods:A total of 82 MM patients from January 1998 to December 2017 in Zhejiang Province were selected to detect the expression of BAP1 protein by immunohistochemical analysis. Kaplan-Meier method was used to draw the survival curve, and multivariate Cox proportional risk model was used to analyze the factors affecting the survival rate.Results:Among 82 MM patients, 61 (74.4%) were female, aged (57±11) years. BAP1 protein expression was deficient in 39 patients (47.6%). The survival rate was correlated with the loss of BAP1 protein expression and age (χ 2=5.27, 5.66, P=0.022, 0.017). Subgroup analysis showed that loss of BAP1 protein expression was associated with better prognosis in MM patients <57 years of age, female, pleural MM, epithelial MM, and treated with drugs or surgery ( P<0.05). Multivariate model results showed that positive expression of BAP1 protein ( HR=3.75, 95% CI: 2.23-6.30, P<0.001) and age ≥57 years ( HR=1.66, 95% CI: 1.01-2.72, P=0.049) were risk factors for survival in patients with MM. Conclusion:Loss of BAP1 protein expression may be an independent prognostic factor in patients with MM, which is associated with longer survival.

Objective:To explore the prognostic value of BRCA1-associated protein 1 (BAP1) expression loss in patients with malignant mesothelioma (MM) .Methods:A total of 82 MM patients from January 1998 to December 2017 in Zhejiang Province were selected to detect the expression of BAP1 protein by immunohistochemical analysis. Kaplan-Meier method was used to draw the survival curve, and multivariate Cox proportional risk model was used to analyze the factors affecting the survival rate.Results:Among 82 MM patients, 61 (74.4%) were female, aged (57±11) years. BAP1 protein expression was deficient in 39 patients (47.6%). The survival rate was correlated with the loss of BAP1 protein expression and age (χ 2=5.27, 5.66, P=0.022, 0.017). Subgroup analysis showed that loss of BAP1 protein expression was associated with better prognosis in MM patients <57 years of age, female, pleural MM, epithelial MM, and treated with drugs or surgery ( P<0.05). Multivariate model results showed that positive expression of BAP1 protein ( HR=3.75, 95% CI: 2.23-6.30, P<0.001) and age ≥57 years ( HR=1.66, 95% CI: 1.01-2.72, P=0.049) were risk factors for survival in patients with MM. Conclusion:Loss of BAP1 protein expression may be an independent prognostic factor in patients with MM, which is associated with longer survival.

Objective:To develop a convolutional neural network based model for assisting pathological diagnoses on thyroid liquid-based cytology specimens.Methods:Seven-hundred thyroid TCT slides were collected, scanned for whole slide imaging (WSI), and divided into training and test sets after labeling the correct diagnosis (benign versus malignant). The extracted regions of interest after noise filtering were cropped into pieces of 512 × 512 patch on 10 × and 40 × magnifications, respectively. A classification model was constructed using deeply learning algorithms, and applied to the training set, then automatically tuned in the test set. After data enhancement and parameters optimization, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the model were calculated. Results The training set with 560 WSI contained 4 926 cell clusters (11 164 patches), while the test set with 140 WSI contained 977 cell clusters (1 402 patches). YOLO network was selected to establish a detection model, and ResNet50 was used as a classification model. With 40 epochs training, results from 10× magnifications showed an accuracy of 90.01%, sensitivity of 89.31%, specificity of 92.51%, positive predictive value of 97.70% and negative predictive value of 70.82%. The area under curve was 0.97. The average diagnostic time was less than 1 second. Although the model for data of 40× magnifications was very sensitive (98.72%), but its specificity was poor, suggesting that the model was more reliable at 10× magnification. Conclusions:The performance of a deep-learning based model is equivalent to pathologists′ diagnostic performance, but its efficiency is far beyond. The model can greatly improve consistency and efficiency, and reduce the missed diagnosis rate. In the future, larger studies should have more morphology diversity, improve model′s accuracy and eventually develop a model for direct clinical use.

Objective:To establish a speech recognition system based on adaptive technology and to evaluate its value in pathological grossing processes.Methods:A total of 600 tissue specimens were collected at the Zhejiang Provincial People's Hospital affiliated to Hangzhou Medical College between October 1, 2020 and December 31, 2020. A speech recognition system based on adaptive technology was used in the pathological grossing processes, and the pathological examination reports were generated and extracted.Results:The speech recognition system based on adaptive technology showed a good recognition rate (overall recognition rate = 77.87%) and helped achieve rapid input and output of pathological examination data.Conclusions:The speech recognition system can reduce the labor costs, improve the work efficiency of pathologists and increase the quality of medical services, which may be valuable for building next-generation smart hospitals.

Objective:To investigate the clinicopathological characteristics and molecular genetics of atypical renal cysts.Methods:Six cases of atypical renal cysts were collected from Zhejiang Provincial People′s Hospital, Hangzhou, China, between February 2014 and February 2019. The clinicopathological characteristics and disease progression were analyzed. The 3p deletion and trisomy of chromosomes 7 and 17 were detected using fluorescence in situ hybridization (FISH).Results:All of the 6 patients were male, aged 43-63 years (median: 52 years). Preoperative Bosniak classification showed 4 cases of grade Ⅱ, 1 case of grade Ⅰ and 1 of grade Ⅲ. Histologically, atypical renal cysts appeared as unilocular or multilocular cysts, lined by multilayered flattened or cuboidal-shaped clear or eosinophilic cells. They often showed short papillary projections, and lacked solid or nodular growth of the lesional cells within the wall or septa of the cysts. Histologically, these cysts could be classified into three categories: acquired cystic disease-associated renal cell carcinoma (ACKD-RCC)-like (3 cases), clear cell type (2 cases), and eosinophilic papillary type (1 case). Two cases of ACKD-RCC-like atypical renal cysts were accompanied by clear cell renal cell carcinomas. On immunohistochemical staining, ACKD-RCC-like atypical renal cysts were focally CK7+/AMACR+/CD57+, the clear-cell type atypical renal cysts were CK7+/CAⅨ+, and eosinophilic papillary type atypical renal cysts were CK7+/AMACR+. FISH analyses showed that one case of ACKD-RCC-like atypical renal cysts had trisomy 17 and one case of clear cell type had 3p deletion, while no signal abnormality was detected in the other cases. The six patients were followed up for 13 to 70 months (median: 27 months), and no evidence of renal cell carcinoma was noted.Conclusion:Atypical renal cysts are a group of lesions that are heterogeneous in clinical, histological and immunophenotypical and molecular genetic features. FISH analyses suggest that a subset of the cases may be precursors of currently known renal cell carcinomas. Extensively sampling and careful observation of the histological characteristics of the cyst wall are important for distinguishing atypical renal cysts from extensively cystic renal cell carcinomas.

Objective: To investigate the clinicopathologic characteristics, immunophenotypes, and differential diagnostic features of extra-pleural solitary fibrous tumor (SFT) with uncommon histology. Methods: Seven cases of extra-pleural SFT with uncommon histology were collected during January 2015 and December 2016 in Zhejiang Provincal People′s Hospital; the clinical and radiologic features, histomorphology, immunophenotype and prognosis were analyzed. EnVision method was used for immunohistochemical staining of STAT6, CD34 and other differential diagnosis associated markers. Results: There were five male and two female patients, age from 23 to 54 years (mean=39 years). Three tumors were located in the soft tissue of head and neck, two in trunk subcutaneous soft tissue, one in sella region, and one in the kidney. Grossly the tumors ranged from 0.4 to 8.0 cm (mean=3.1 cm). Microscopically, all three head and neck cases resembled giant cell angiofibroma/giant cell subtype SFT, and one case showed sheet-like pattern of the multinucleated syncytial cells, creating a biphasic arrangement similar to myofibroma. Both truncal tumor resembled lipomatous type SFT, with one similar to dermatofibrosarcoma protuberans and the other to atypical spindle cell lipomatous tumor. The sella tumor showed morphology of a conventional SFT with high grade sarcomatous transformation. The renal tumor demonstrated a malignant SFT with entrapped benign renal tubules, mimicking a biphase synovial sarcoma or a malignant mixed epithelial and stromal tumor. By immunohistochemistry, all seven SFTs showed diffuse and strong nuclear reactivity to antibody against STAT6. Conclusions Extra-pleural SFTs show a significant heterogeneity of morphology and biological behavior which could cause differential confusion.Careful attention to its characteristic histomorphology with the use of STAT6 immunohistochemistry can help distinguish this tumor from its many mimickers.