Systemic mastocytosis (SM) with an associated myelodysplastic/myeloproliferative neoplasm (MDS/MPN) is a rare subtype of myeloid neoplasms. Avapritinib, a potent and selective inhibitor of KIT D816V, is approved for treating advanced systemic mastocytosis (AdvSM). We report a case of a patient with SM and an associated MDS/MPN treated with avapritinib. The patient achieved sustained complete remission (CR) of SM, with persistent molecular negativity for the KIT D816V mutation, but ultimately succumbed to disease progression to chronic myelomonocytic leukemia (CMML). Although avapritinib, a novel targeted therapy, has significantly improved outcomes for SM, the efficacy of treatment for the associated hematologic neoplasm in patients with SM-AHN may be the primary determinant of long-term overall survival and progression-free survival. This report includes a review of relevant literature to provide insights into the clinical diagnosis and management of this rare entity.

Objective:To explore the clinical features and molecular characteristics of myeloproliferative neoplasms (MPNs) patients with NFE2 gene mutations.Methods:Gene targeted sequencing was used to detect NFE2 gene mutation in 723 patients diagnosed with MPNs who were admitted to Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College between April 2021 and June 2023. The association between NFE2 gene mutations and clinical features and molecular characteristics of MPNs patients were retrospectively analyzed.Results:Among 723 patients with MPNs, NFE2 gene mutations were found in 41 cases (5.7%) . NFE2 gene mutations were predominantly frameshift mutations (44.4%) , followed by nonsense mutations (33.3%) . The median number of mutations in patients with NFE2 gene mutations (4 [2,5]) was higher compared to the group without NFE2 gene mutations (2, [1,3]) ( P<0.001) . NFE2 gene mutations frequently co-occurred with mutations in MPL, ATM, PPM1D, and TET1. NFE2 gene mutations were mostly sub-clonal events, with 80.5% occurring after MPNs driver mutations (JAK2, CALR, or MPL) . NFE2 mutations were correlated with older age [median age: 60 (54, 67) years vs 54 (41, 63) years, P=0.001]. Patients with NFE2 gene mutations had a higher incidence of pre-diagnosis thrombosis (39.0% vs 22.0%, P=0.012) and pre-diagnosis arterial thrombosis (36.6% vs 20.4%, P=0.014) . Using a logistic regression analysis model adjusting for age and comorbidities (including chronic infections, malignancies, and autoimmune diseases) , NFE2 gene mutation was identified as an independent determinant of elevated tumor necrosis factor-alpha (TNF-α) ( OR=2.747, 95% CI: 1.143-6.605, P=0.024) , interferon-gamma (IFN-γ) ( OR=2.689, 95% CI: 1.191-6.076, P=0.017) , IL-10 ( OR=3.219, 95% CI: 1.343-7.717, P=0.009) , IL-12P70 ( OR=3.397, 95% CI:1.003-11.508, P=0.049) , IL-17 ( OR=2.284, 95% CI: 1.017-5.127, P=0.045) . In polycythaemia vera (PV) patients with the NFE2 gene mutation, the proportion of those classified as high-risk is notably higher in both the IWG-PV and mutation-enhanced international prognostic systems for PV (MIPSS-PV) (66.7% vs 25.3% for IWG-PV, P=0.033; 22.2% vs 2.0% for MIPSS-PV, P=0.013) . Similarly, for essential thrombocythaemia (ET) patients, the proportion in the high-risk group of the mutation-enhanced international prognostic systems for ET (MIPSS-ET) is significantly higher (15.4% vs 6.1%, P=0.021) . No statistically significant differences were observed in overall survival or cumulative incidence of thrombosis between NFE2-mutated (38 cases) and non-mutated MPNs patients (671 cases, P>0.05) . Conclusion:NFE2 gene mutations in MPNs were predominantly frameshift mutations. NFE2 gene mutations were correlated with older age, elevated levels of several inflammatory factors (including TNF-α、IFN-γ、IL-10、IL-12P70、IL-17) , and they mostly occurred in late-stage of MPNs.

Systemic mastocytosis (SM) with an associated myelodysplastic/myeloproliferative neoplasm (MDS/MPN) is a rare subtype of myeloid neoplasms. Avapritinib, a potent and selective inhibitor of KIT D816V, is approved for treating advanced systemic mastocytosis (AdvSM). We report a case of a patient with SM and an associated MDS/MPN treated with avapritinib. The patient achieved sustained complete remission (CR) of SM, with persistent molecular negativity for the KIT D816V mutation, but ultimately succumbed to disease progression to chronic myelomonocytic leukemia (CMML). Although avapritinib, a novel targeted therapy, has significantly improved outcomes for SM, the efficacy of treatment for the associated hematologic neoplasm in patients with SM-AHN may be the primary determinant of long-term overall survival and progression-free survival. This report includes a review of relevant literature to provide insights into the clinical diagnosis and management of this rare entity.

Objective:To explore the clinical features and molecular characteristics of myeloproliferative neoplasms (MPNs) patients with NFE2 gene mutations.Methods:Gene targeted sequencing was used to detect NFE2 gene mutation in 723 patients diagnosed with MPNs who were admitted to Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College between April 2021 and June 2023. The association between NFE2 gene mutations and clinical features and molecular characteristics of MPNs patients were retrospectively analyzed.Results:Among 723 patients with MPNs, NFE2 gene mutations were found in 41 cases (5.7%) . NFE2 gene mutations were predominantly frameshift mutations (44.4%) , followed by nonsense mutations (33.3%) . The median number of mutations in patients with NFE2 gene mutations (4 [2,5]) was higher compared to the group without NFE2 gene mutations (2, [1,3]) ( P<0.001) . NFE2 gene mutations frequently co-occurred with mutations in MPL, ATM, PPM1D, and TET1. NFE2 gene mutations were mostly sub-clonal events, with 80.5% occurring after MPNs driver mutations (JAK2, CALR, or MPL) . NFE2 mutations were correlated with older age [median age: 60 (54, 67) years vs 54 (41, 63) years, P=0.001]. Patients with NFE2 gene mutations had a higher incidence of pre-diagnosis thrombosis (39.0% vs 22.0%, P=0.012) and pre-diagnosis arterial thrombosis (36.6% vs 20.4%, P=0.014) . Using a logistic regression analysis model adjusting for age and comorbidities (including chronic infections, malignancies, and autoimmune diseases) , NFE2 gene mutation was identified as an independent determinant of elevated tumor necrosis factor-alpha (TNF-α) ( OR=2.747, 95% CI: 1.143-6.605, P=0.024) , interferon-gamma (IFN-γ) ( OR=2.689, 95% CI: 1.191-6.076, P=0.017) , IL-10 ( OR=3.219, 95% CI: 1.343-7.717, P=0.009) , IL-12P70 ( OR=3.397, 95% CI:1.003-11.508, P=0.049) , IL-17 ( OR=2.284, 95% CI: 1.017-5.127, P=0.045) . In polycythaemia vera (PV) patients with the NFE2 gene mutation, the proportion of those classified as high-risk is notably higher in both the IWG-PV and mutation-enhanced international prognostic systems for PV (MIPSS-PV) (66.7% vs 25.3% for IWG-PV, P=0.033; 22.2% vs 2.0% for MIPSS-PV, P=0.013) . Similarly, for essential thrombocythaemia (ET) patients, the proportion in the high-risk group of the mutation-enhanced international prognostic systems for ET (MIPSS-ET) is significantly higher (15.4% vs 6.1%, P=0.021) . No statistically significant differences were observed in overall survival or cumulative incidence of thrombosis between NFE2-mutated (38 cases) and non-mutated MPNs patients (671 cases, P>0.05) . Conclusion:NFE2 gene mutations in MPNs were predominantly frameshift mutations. NFE2 gene mutations were correlated with older age, elevated levels of several inflammatory factors (including TNF-α、IFN-γ、IL-10、IL-12P70、IL-17) , and they mostly occurred in late-stage of MPNs.

The multi-campus mode is an important way to give full play to the advantages of public hospitals and promote the expansion of high-quality medical resources and balanced regional layout. The authors summarized the practical experience of the Second Affiliated Hospital Zhejiang University School of Medicine in promoting multi-campus cultural integration, including vertical dimensional initiatives including raising cultural construction to a strategic level, improving the working mechanism of cultural construction, and building a distinctive cultural identity system; horizontal dimensional initiatives including creating equal status and intergroup cooperation conducive to cultural integration, building a variety of forms of the main cultural communication platform, and building a unified and diverse cross-campus communication bridge. Through cultural integration, the internal cohesion of the hospital was enhanced and the influence of the hospital brand was improved. The authors suggested that cultural integration should always be based on the principle of " seeking common ground while preserving minor differences" , focusing on the construction of systems and standards, and focusing on the construction of communication platforms.

Objective:To develop 2 prediction models for anti-tuberculosis drug-induced liver injury (ATB-DILI) based on convolutional neural network (CNN) and multiple logistic regression, and to evaluate and compare the performance of the 2 models.Methods:The clinical and laboratory test data of inpatients in the Third People′s Hospital of Zhenjiang, Jurong People's Hospital, and the Third People′s Hospital of Danyang from January 1, 2019 to October 31, 2022 were collected. According to whether ATB-DILI occurred, patients were divided into with and without ATB-DILI groups, and the clinical characteristics of the 2 groups were compared. The patients were randomly divided into training set and test set according to a ratio of 7∶3 by random number table method. Based on data in the training set, multiple logistic regression and CNN were used to develop ATB-DILI prediction models; based on data in the training and test sets, the accuracy of the 2 models in predicting ATB-DILI was verified. The receiver operating characteristic (ROC) curve was drawn, and the sensitivity, specificity, Youden index and area under the curve (AUC) of the 2 models were compared.Results:A total of 3 012 patients were included in the study, of which 294 (9.76%) were diagnosed with ATB-DILI; 2 108 patients were in the training set and 904 in the test set. The results of multiple logistic regression analysis showed that age, history of liver diseases, hypoalbuminemia, and no preventive use of liver protection drugs were independent risk factors for the occurrence of ATB-DILI. Based on these risk factors, multiple logistic regression model equations were constructed. The results of deep learning and analyzing the patient data of the training set by CNN showed that the top 5 risk factors that had the greatest impact on the occurrence of ATB-DILI were history of liver disease, age, no preventive use of liver protection drugs, hypoalbuminemia, and alcohol consumption. The CNN model was constructed according to the top 5 risk factors. The total accuracy in predicting the occurrence of ATB-DILI in the training and test sets using the multiple logistic regression model was 87.62% and 88.27%, respectively, and the total accuracy of using CNN model was 92.36% and 91.70%, respectively. The sensitivity, specificity, and AUC of the CNN model were all higher than those of the multiple logistic regression model, and the differences were statistically significant (all P<0.05). Conclusion:Both the multiple logistic regression model and CNN model have good predictive performance for the occurrence of ATB-DILI, and the prediction performance of CNN model is better, comparatively.

Objective:To develop 2 prediction models for anti-tuberculosis drug-induced liver injury (ATB-DILI) based on convolutional neural network (CNN) and multiple logistic regression, and to evaluate and compare the performance of the 2 models.Methods:The clinical and laboratory test data of inpatients in the Third People′s Hospital of Zhenjiang, Jurong People's Hospital, and the Third People′s Hospital of Danyang from January 1, 2019 to October 31, 2022 were collected. According to whether ATB-DILI occurred, patients were divided into with and without ATB-DILI groups, and the clinical characteristics of the 2 groups were compared. The patients were randomly divided into training set and test set according to a ratio of 7∶3 by random number table method. Based on data in the training set, multiple logistic regression and CNN were used to develop ATB-DILI prediction models; based on data in the training and test sets, the accuracy of the 2 models in predicting ATB-DILI was verified. The receiver operating characteristic (ROC) curve was drawn, and the sensitivity, specificity, Youden index and area under the curve (AUC) of the 2 models were compared.Results:A total of 3 012 patients were included in the study, of which 294 (9.76%) were diagnosed with ATB-DILI; 2 108 patients were in the training set and 904 in the test set. The results of multiple logistic regression analysis showed that age, history of liver diseases, hypoalbuminemia, and no preventive use of liver protection drugs were independent risk factors for the occurrence of ATB-DILI. Based on these risk factors, multiple logistic regression model equations were constructed. The results of deep learning and analyzing the patient data of the training set by CNN showed that the top 5 risk factors that had the greatest impact on the occurrence of ATB-DILI were history of liver disease, age, no preventive use of liver protection drugs, hypoalbuminemia, and alcohol consumption. The CNN model was constructed according to the top 5 risk factors. The total accuracy in predicting the occurrence of ATB-DILI in the training and test sets using the multiple logistic regression model was 87.62% and 88.27%, respectively, and the total accuracy of using CNN model was 92.36% and 91.70%, respectively. The sensitivity, specificity, and AUC of the CNN model were all higher than those of the multiple logistic regression model, and the differences were statistically significant (all P<0.05). Conclusion:Both the multiple logistic regression model and CNN model have good predictive performance for the occurrence of ATB-DILI, and the prediction performance of CNN model is better, comparatively.

AIM:To investigate the ability of a metal complex ammonium tetrathiomolybdate (ATTM) to re-lease H2 S and its cytoprotective effect on an oxidative injury model .METHODS:Released H2 S was absorbed in a reaction flask from ATTM dissolved in the cell medium .Staining with dichlorodihydrofluorescein diacetate or rhodamine 123 fol-lowed by photofluorography was conducted for the observation of reactive oxygen species ( ROS) and mitochondrial mem-brane potential (ΔΨm) levels, respectively.Cell viability and release of lactate dehydrogenase (LDH) from the cells were measured with commercial kits.RESULTS:Similar to another H2S donor GYY4137, ATTM had an ability to release H2S in the cell medium in a dose-dependent manner .Treatment of human skin HaCaT cells with ATTM at concentrations of 25~400 μmol/L didn’ t significantly alter cell viability .Exposure of the cells to ultraviolet rays or a ROS donor H 2 O2 in-creased the intracellular ROS levels .Treatment with 400 μmol/L H2 O2 significantly reduced the viability of HaCaT cells (P<0.01).However, before the treatment with H2O2, pretreatment with ATTM at 100 and 200 μmol/L markedly pre-vented the H2O2-induced cell injury (P<0.01).In addition, the treatment with H2O2 triggeredΔΨm loss (P<0.01) and LDH release from the cells (P<0.01).Prior to suffering from H2O2 injury, the preconditioning with 200 μmol/L ATTM significantly improved ΔΨm levels ( P<0.05 ) and attenuated LDH release from the cells ( P<0.01 ) .CONCLUSION:ATTM is capable of releasing H 2 S and protecting human skin cells against oxidative injury .

Brucella ; isolation & purification ; Brucellosis ; epidemiology ; China ; epidemiology ; Humans

OBJECTIVETo research the effects of moschus, borneol, styrax and benzoinum on the structure and function of blood brain barrier in cerebral ischemia-reperfusion injury model rats.

METHODFocal middle cerebral artery occlusion (MCAO) was introduced as an in vivo ischemic model in rats. After 2 h MCAO, nylon suture was pulled up 1 cm to give blood reperfusion. After 22 h reperfusion, all animals were decapitated. The ultramicrostructure of blood brain barrier of ischemia hemisphere side in fronto-parietal cortex region by transmission electron microscope, and the content of VEGF and MMP-9 in ischemia side brain tissue were measured by ELISA.

RESULTIn model and solvent group rats, the capillary endothelium cells, astro-glial cells and nerve cells in ischemia hemisphere side in fronto-parietal region were emerged in different degree compared with sham-operated groups, which exhibited tight junction between endothelial cells being opened, basal lamina being dissolved, and permeability increasing, and cellularedema. In borneol (0.2 g x kg(-1)) group rats, the structure of three kinds of cells were nearly normal, which tight junction structure was clear, rough endoplasmic reticulum and polyribosome could be found in cytoplasm. In moschus (66.6 mg x kg(-1)) group rats, the structure of capillary endothelium cells and astrocytes were nearly normal as well as the basal lamina, but the electrons in neurons was maldistribution. In styrax (1.332 g x kg(-1)) group rats, astrocytes were nearly normal, while capillary endothelial cells and neurons exhibited oedema in different degrees. And the basal lamina was discontinuous, augmentation of cell spaces in endothelial cells increased the permeability, some endoplasmic reticulum broadened and ribosome ablated. In benzoinum (1.0 g x kg(-1)) group rats, oedema of capillary endothelial cells and astrocytes was significant, basal lamina broke. Meanwhile endoplasmic reticulum broadened as vacuole, the number of ribosome in rough endoplasmic reticulum decreased, crista mitochondriales in some neurons disappeared as vacuole which hint oedema happened. Results also showed that borneol decrease the level of VEGF in ischemia side brain tissue significantly, while has little influence on the level of MMP-9. Moschus showed the tendency to decrease the level of VEGF and MMP-9 in ischemia side brain tissue.

CONCLUSIONAromatic resuscitation drugs showed the protection effect on blood brain barrier in cerebral ischemia-reperfusion injury rats, which the protection effect of moschus and borneol were better than that of styrax and benzoinum. The mechanism of protection effect maybe related to decrease the level of VEGF and MMP-9.

Animals ; Benzoin ; pharmacology ; Blood-Brain Barrier ; drug effects ; metabolism ; ultrastructure ; Bornanes ; pharmacology ; Brain Ischemia ; drug therapy ; metabolism ; Disease Models, Animal ; Fatty Acids, Monounsaturated ; pharmacology ; Infarction, Middle Cerebral Artery ; drug therapy ; metabolism ; Male ; Matrix Metalloproteinase 9 ; drug effects ; metabolism ; Neuroprotective Agents ; pharmacology ; Plant Extracts ; pharmacology ; Rats ; Reperfusion Injury ; drug therapy ; metabolism ; Styrax ; chemistry ; Vascular Endothelial Growth Factor A ; drug effects ; metabolism