Purpose: Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients. Materials and Methods: In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs. Conclusion Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

Purpose: Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients. Materials and Methods: In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs. Conclusion Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

Purpose: Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients. Materials and Methods: In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs. Conclusion Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

Objective To explore the differences in tremor characteristics between patients with primary Parkinson's disease(IPD),essential tremor(ET),and Parkinson's disease developed from essential tremor(ET-PD).Method Thirty IPD patients,30 ETs,and 20 ET-PD patients were included,and the frequency,contraction pattern,and presence of harmonics of static and postural tremors were compared among the three groups.Results There were statistically significant differences(P<0.01)among the IPD group,ET group,and ET-PD group in terms of age of onset,disease course,and the unified Parkinson's disease rating scale(UPDRS)score.There were statistically significant differences(P<0.05)in the average frequency of stationary tremors,average frequency of postural tremors,rate of alternating tremors in stationary state,rate of alternating tremors in postural state,and rate of harmonic occurrence in stationary state among the IPD group,ET group,and ET-PD group,as well as in the rate of harmonic occurrence in postural state(P<0.05).Conclusion The IPD group,ET group,and ET-PD group each have significant differences in tremor characteristics.The ET-PD group has both characteristics and uniqueness,and tremor analysis can help identify this disease.

ObjectiveIn order to improve the recognition accuracy of named entities in medical record texts and realize the effective mining and utilization of medical record knowledge， a Bert-Radical-Lexicon（BRL） neural network model is constructed to recognize medical record entities with respect to the characteristics of medical record texts. MethodWe selected 408 medical records related to hypertension from the the Complete Library of Famous Medical Records of Chinese Dynasties and constructed a dataset consisting of 1 672 medical records by manually labeling. Then， we randomly divided the dataset into three subsets， including the training set（1 004 cases）， the testing set （334 cases） and the validation set（334 cases）. Based on this dataset， we built a BRL model that fused various text features of medical records， as well as its variants BRL-B， BRL-L and BRL-R， and a baseline model Base for experiments. During the model training phase， we trained the above models using the training set to reduce the risk of overfitting. We continuously monitored the performance of each model on the validation set during training and saved the model with the best performance. Finally， we evaluated the performance of these models on the testing set. ResultCompared with other models， the BRL model had the best performance in the medical records named entity recognition task， with an overall recognition precision of 90.09%， a recall of 90.61%， and the harmonic mean of the precision and recall（F1） of 90.35% for eight types of entities， including disease， symptom， tongue manifestation， pulse condition， syndrome， method of treatment， prescription and traditional Chinese medicine（TCM）. Compared with the Base model， the BRL model improved the overall F1 value of entity recognition by 5.22%， and the F1 value of pulse condition entity increased by 6.92%， which was the largest increase. ConclusionBy incorporating a variety of medical record text features in the embedding layer， the BRL neural network model has stronger named entity recognition ability， and thus extracts more accurate and reliable TCM clinical information.

For two young female patients with extramedullary recurrence of reproductive system after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia. And the characteristics of extramedullary relapse of reproductive system are summarized for exploring possible effective treatments.

Retinoic acid (RA) is a metabolic intermediate of vitamin A, which plays an important role in embryonic development and cell growth and differentiation. Cellular retinoic acid-binding proteins 2 (CRABP2) are a group of low-molecular weight intracellular proteins whose primary physiological function is to transport RA to the nucleus. Generally, CRABP2 binds to the retinoic acid receptor (RAR), then regulates specific downstream signaling pathways to function. Abnormal expression of CRABP2 was closely related to several human malignant tumors, and could affect the tumor occurrence and development through regulating multiple growth or apoptosis associated pathways or key biological molecules. Therefore, CRABP2 may be considered as a new diagnostic and prognostic marker for cancer, and a new therapeutic target for malignant tumors. Our present article summarizes the relationship between CRABP2 and tumor progression, drug resistance and prognosis, so as to provide reference for the future research.

Objective:To investigate the distribution of pathogenic bacteria of bloodstream infection after chemotherapy in patients with acute leukemia (AL), to analyze the risk factors for the occurrence of adverse events and to construct a nomogram model to predict the occurrence of adverse events.Methods:The clinical data of 313 AL patients with bloodstream infection who were admitted to the First Hospital of Jilin University from January 2018 to December 2020 were retrospectively analyzed, and the incidence, fatality and distribution characteristics of pathogenic bacteria after chemotherapy in AL patients were analyzed; the occurrence of adverse events (death or infectious shock) in patients with different clinicopathological characteristics were compared. Unconditional logistic binary regression model multifactor analysis was used to screen independent risk factors for the occurrence of adverse events in AL patients with bloodstream infection after chemotherapy; the nomogram model for predicting the occurrence of adverse events was developed by using R software; the Hosmer-Lemeshow test was used to verify the predictive effect of the model.Results:Of the 313 AL patients, the overall fatality rate was 4.2% (13/313), the all-cause fatality rate of bloodstream infection was 3.5% (11/313). Of the 313 cases, 254 cases (81.1%) were Gram-negative bacteria infection, mainly including 115 cases (45.3%) of Escherichia coli, 80 cases (31.5%) of Klebsiella pneumoniae, and 29 cases (11.4%) of Pseudomonas aeruginosa, and 10 cases (3.9%) died; 51 cases (16.3%) were Gram-positive cocci infection, mainly including 22 cases (43.1%) of Streptococcus spp., 20 cases (39.2%) of Staphylococcus spp., 7 cases (13.7%) of Enterococcus faecalis, and 0 case died; 8 cases (2.6%) were fungal infection, including 4 cases (1.3%) of Candida tropicalis, 2 cases (0.6%) of Candida subsmoothis, 1 case (0.3%) of Candida smooth, 1 case (0.3%) of new Cryptococcus, and 3 cases (37.5%) died. The differences in the occurrence rates of adverse events were statistically significant when comparing different treatment stage, risk stratification, timing of sensitive antibiotic use, total duration of fever, and glucocorticoid use in chemotherapy regimen, infecting bacteria carbapenem resistance, and leukemia remission (all P < 0.05). The results of logistic binary regression analysis showed that the use of glucocorticoid in chemotherapy regimen, the total duration of fever ≥7 d, the timing of sensitive antibiotic use ≥24 h, and carbapenem resistance of the infecting bacteria were independent risk factors for the occurrence of adverse events in AL patients with bloodstream infection after chemotherapy (all P < 0.05). A nomogram prediction model for the occurrence of adverse events in AL patients with bloodstream infection was established, and the nomogram model was calibrated and validated with good calibration and discrimination. Conclusions:The pathogenic bacteria of bloodstream infection after chemotherapy in AL patients is mainly Gram-negative bacteria, and the presence of glucocorticoid in chemotherapy regimen, long total duration of fever, poor timing of sensitive antibiotics, and infecting bacteria carbapenem resistance are risk factors for the occurrence of adverse events in AL patients with bloodstream infection after chemotherapy, and the nomogram prediction model based on these factors has a reliable predictive ability for the occurrence of adverse events.

ObjectiveTo achieve high-dimensional prediction of class imbalanced of adverse drug reaction（ADR） of traditional Chinese medicine（TCM） and to classify and identify risk factors affecting the occurrence of ADR based on the post-marketing safety data of TCM monitored centrally in real world hospitals. MethodThe ensemble clustering resampling combined with regularized Group Lasso regression was used to perform high-dimensional balancing of ADR class-imbalanced data， and then to integrate the balanced datasets to achieve ADR prediction and the risk factor identification by category. ResultA practical example study of the proposed method on a monitoring data of TCM injection performed that the accuracy of the ADR prediction， the prediction sensitivity， the prediction specificity and the area under receiver operating characteristic curve（AUC） were all above 0.8 on the test set. Meanwhile， 40 risk factors affecting the occurrence of ADR were screened out from total 600 high-dimensional variables. And the effect of risk factors on the occurrence of ADR was identified by classification weighting. The important risk factors were classified as follows：past history， medication information， name of combined drugs， disease status， number of combined drugs and personal data. ConclusionIn the real world data of rare ADR with a large amount of clinical variables， this paper realized accurate ADR prediction on high-dimensional and class imbalanced condition， and classified and identified the key risk factors and their clinical significance of categories， so as to provide risk early warning for clinical rational drug use and combined drug use， as well as scientific basis for reevaluation of safety of post-marketing TCM.

Objective:To explore the characteristics of BCR-ABL1 kinase domain mutations in imatinib-resistant chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) patients from Northeast China and their impact on prognosis. Methods:The clinical data of 252 CML patients and 49 Ph + ALL patients who were admitted to the First Hospital of Jilin University from January 2013 to October 2018 were retrospectively analyzed. The samples of bone marrow or peripheral blood were collected from patients when imatinib treatment was not effective. Nested polymerase chain reaction (PCR) was used to amplify the BCR-ABL1 kinase domain, and Sequencing Analysis v5.4 software was used to analyze the mutation of BCR-ABL1 kinase domain. Patients were followed up for 6-48 months, and the survival analysis was performed. Results:Among 252 CML patients, the mutations in ABL1 kinase domain were found in 57 patients (22.6%), including 25 patients in the chronic phase, 21 patients in the accelerated phase and 11 patients in the blast crisis; 50 patients had 20 types of single point mutation, and the most common mutation types were E255K (16.0%, 8/50), T315I (14.0%, 7/50), M244V (8.0%, 4/50) and G250E (8.0%, 4/50), which were all concentrated in the P-loop and C-helix domains; 7 patients had double mutations; patients with multiple mutations had the worst prognosis, with a median overall survival (OS) time of 3.2 months. Among 49 Ph + ALL patients, 17 cases (34.7%) were positive for mutations in the BCR-ABL1 kinase domain, 14 patients had 12 types of single point mutation, and 3 patients had multiple mutations; the median OS time of patients with multiple mutations, mutations located in the P-loop and C-helix domains and mutations located in the other domains was 2.0, 8.0 and 18.0 months, and the difference in OS among the three groups was statistically significant ( P < 0.01). Conclusions:Among the imatinib-resistant CML and Ph + ALL patients from Northeast China, point mutations in the P-loop and C-helix domains are most commonly found. Multiple mutations, mutations in the P-loop and C-helix domains are related to the poor prognosis of the patients.