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.

Objective To explore the optimisation path of medical resource allocation efficiency improvement in Traditional Chinese Medicine (TCM) hospitals under the synergistic effect of multiple factors,so as to provide powerful support for the balanced development of medical resources in TCM hospitals.Methods The comprehensive efficiency of resource allocation in TCM hospitals in 31 provinces (cities and districts) of China obtained by Data Envelopment Analysis was taken as the outcome variable,and with the help of Fuzzy-set Qualitative Comparative Analysis,it examined the configurations of efficient medical resource allocation,considering the following conditional variables:per capital Regional GDP,the proportion of fiscal allocation revenue to total income,the ratio of TCM practicing (assistant) physicians to all practicing (assistant) physicians,the average length of hospital stay for discharged patients,the number of total diagnosis and treatments per thousand population,and the number of hospital beds per thousand population.Results By analyzing the conditional patterns of efficient allocation of medical resources in TCM hospitals,three equivalent driving paths can be summarized,which are comprehensive service capacity,TCM advantage and hospitalization driving paths.Conclusion The overall level of medical resource allocation efficiency of TCM hospitals in China needs to be improved.In the future,efforts should be made to improve the comprehensive service capacity and operational efficiency of hospitals,give full play to the advantages of TCM,build a high-quality TCM talent team,reasonably shorten the average hospital stay,and improve the utilization efficiency of hospital beds.

Objective To explore the optimisation path of medical resource allocation efficiency improvement in Traditional Chinese Medicine (TCM) hospitals under the synergistic effect of multiple factors,so as to provide powerful support for the balanced development of medical resources in TCM hospitals.Methods The comprehensive efficiency of resource allocation in TCM hospitals in 31 provinces (cities and districts) of China obtained by Data Envelopment Analysis was taken as the outcome variable,and with the help of Fuzzy-set Qualitative Comparative Analysis,it examined the configurations of efficient medical resource allocation,considering the following conditional variables:per capital Regional GDP,the proportion of fiscal allocation revenue to total income,the ratio of TCM practicing (assistant) physicians to all practicing (assistant) physicians,the average length of hospital stay for discharged patients,the number of total diagnosis and treatments per thousand population,and the number of hospital beds per thousand population.Results By analyzing the conditional patterns of efficient allocation of medical resources in TCM hospitals,three equivalent driving paths can be summarized,which are comprehensive service capacity,TCM advantage and hospitalization driving paths.Conclusion The overall level of medical resource allocation efficiency of TCM hospitals in China needs to be improved.In the future,efforts should be made to improve the comprehensive service capacity and operational efficiency of hospitals,give full play to the advantages of TCM,build a high-quality TCM talent team,reasonably shorten the average hospital stay,and improve the utilization efficiency of hospital beds.

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.

Objective By studying the changes in the institutional distribution of curative care expenditure(CCE)of the elderly population before and after the comprehensive reform medical-pharmaceutical separation and linkage of medical consumption,it provided data reference for the next step of accurately optimizing the elderly patients flow.Methods A multi-stage stratified whole-group sampling survey was used to select the sample.A System of Health Accounts 2011 was used to calculate the CCE of elderly patients in medical institutions.Results The CCE of medical institutions for the elderly population in Beijing increased from 60.457 billion yuan to 797.54 billion yuan,with an average annual growth rate of 6.83%,the fastest growth rate of 24.04%for community-based health treat-ment center.The percentage of CCE in the community increased from 11.31%to 17.71%,while the percentage of CCE in tertiary hospitals decreased by 4.39 percentage points.The flow of CCE for outpatient patients was obviously opti-mized.Younger elderly outpatient patients are more willing to seek treatment in the community,but the flow di-rection of outpatient treatment for elderly patients is more optimized.The CCE fpr elderly outpatient patients with chronic diseases such as endocrine,nutritional and metabolic diseases and nervous system diseases have been substantially transferred to the community-based health center.Conclusion The reform has different impacts on the treatment of elderly patients with different genders,ages and diseases.It is necessary to strengthen the service capacity building of primary medical institutions,highlight the development characteristics of secondary hospitals,and accurately improve the hierarchical diagnosis and treatment system for elderly patients.

Objective:A nationwide multi-center and large sample survey was conducted to compare the validity of the Mini International Neuropsychiatric Interview (Hypo-) Manic Episode with Mixed Features-DSM-5 Module (MINI-M) questionnaire and the Clinically Useful Depression Outcome Scale Supplemented with Questions for the DSM-5 Mixed Features Specifier (CUDOS-M) depression subscale in identifying mixed features in patients experiencing (hypo-) manic episodes.Methods:Using a convenience sampling method, 366 patients with bipolar disorder experiencing acute (hypo-) manic episodes who met the inclusion and exclusion criteria were recruited. The diagnosis of "with mixed features" was based on the DSM-5 criteria for mixed features. The predictive validity of the MINI-M questionnaire and the CUDOS-M depression subscale to screen mixed features was analyzed using the receiver operating characteristic (ROC) curve. Additionally, the difference in area under the ROC curve (AUC) between the two instruments was compared.Results:The AUC for the MINI-M questionnaire and the CUDOS-M depression subscale in screening mixed features were 0.79 (95 %CI=0.75-0.84) and 0.81 (95 %CI=0.77-0.86), respectively. There was no statistically significant difference in AUC between the two measurements ( Z=-1.19, P>0.05). Among patients with acute (hypo-) manic episodes, 45.9% (168/366) presented with mixed features according to the DSM-5 criteria, while the corresponding figures were 43.7% (160/366) using the MINI-M questionnaire (total score≥3) and 42.1% (154/366) using the CUDOS-M depression subscale (total score≥20). Screening results were comparable among the three measures. Conclusion:Mixed features are common among patients experiencing acute (hypo-) manic episodes. The MINI-M questionnaire and the CUDOS-M depression subscale demonstrate equivalent validity in identifying mixed features.

Objective:A nationwide multi-center and large sample survey was conducted to compare the validity of the Mini International Neuropsychiatric Interview (Hypo-) Manic Episode with Mixed Features-DSM-5 Module (MINI-M) questionnaire and the Clinically Useful Depression Outcome Scale Supplemented with Questions for the DSM-5 Mixed Features Specifier (CUDOS-M) depression subscale in identifying mixed features in patients experiencing (hypo-) manic episodes.Methods:Using a convenience sampling method, 366 patients with bipolar disorder experiencing acute (hypo-) manic episodes who met the inclusion and exclusion criteria were recruited. The diagnosis of "with mixed features" was based on the DSM-5 criteria for mixed features. The predictive validity of the MINI-M questionnaire and the CUDOS-M depression subscale to screen mixed features was analyzed using the receiver operating characteristic (ROC) curve. Additionally, the difference in area under the ROC curve (AUC) between the two instruments was compared.Results:The AUC for the MINI-M questionnaire and the CUDOS-M depression subscale in screening mixed features were 0.79 (95 %CI=0.75-0.84) and 0.81 (95 %CI=0.77-0.86), respectively. There was no statistically significant difference in AUC between the two measurements ( Z=-1.19, P>0.05). Among patients with acute (hypo-) manic episodes, 45.9% (168/366) presented with mixed features according to the DSM-5 criteria, while the corresponding figures were 43.7% (160/366) using the MINI-M questionnaire (total score≥3) and 42.1% (154/366) using the CUDOS-M depression subscale (total score≥20). Screening results were comparable among the three measures. Conclusion:Mixed features are common among patients experiencing acute (hypo-) manic episodes. The MINI-M questionnaire and the CUDOS-M depression subscale demonstrate equivalent validity in identifying mixed features.

Eutrophils are the first innate immune cells to reach the site of inflammation. Neutrophils produce neutrophil extracellular traps (NETs) that can quickly capture and limit the spread of pathogens, facilitating the removal of pathogens and their debris. Neutrophils in the oral cavity are specifically transformed from circulating neutrophils in the blood, and the number of NETs released by oral neutrophils is much higher than that of circulating neutrophils, thus better maintaining the balance of the oral microenvironment. As a bimorphic fungus, only the mycelium phase of Candida albicans can induce NETs, which is related to the neutrophils' ability to sense the size of pathogenic microorganisms through neutrophil elastase. However, spherical Staphylococcus aureus are much smaller than Candida albicans, and they can still induce NETs. Porphyromonas gingivalis, as one of the microorganisms in the periodontitis complex, induces fewer NETs than Streptococcus oralis and Actinomycetes, which are two common oral microorganisms, and there may be a mechanism allowing them to escape neutrophilic immunity in the early stage of periodontitis. Although the two main pathways of NET production have been studied in detail, the mechanisms involved in the induction of NETs by different microorganisms, especially from oral neutrophils, are not well understood. This review describes the mechanism of the immune effects of pathogenic microorganisms on neutrophil NETs in the oral cavity, providing a reference for the search for therapeutic targets and the development of key drugs for treating oral infectious diseases.

Objective:This study investigates the difference in the detection rate and symptomatology between ICD-10 and DSM-5 diagnostic criteria for bipolar disorder with mixed states.Methods:Based on the Phase Ⅰ (2012) and Phase Ⅱ (2021) databases of National Bipolar Mania Pathway Survey (BIPAS), patients with bipolar disorder were included. General demographic data, clinical characteristics, symptomatic phenotypes, and mixed characteristics were retrieved. The detection rates and symptomatic performances of patients with or without mixed states in Phase Ⅰ and Ⅱ were compared using the chi-square test.Results:For patients with mixed states, the detection rate during Phase Ⅱ (2021) using DSM-5 (18.79%, 199/1 059) criteria was significantly higher than that during Phase Ⅰ (2012) using ICD-10 (6.78%, 199/2 934; χ 2=125.05, P<0.001). Whether using ICD-10 or DSM-5 criteria, patients with mixed states had a significantly higher frequency of multiple symptomatic manifestations. Conclusion:The DSM-5 diagnostic criteria generate a high detection rate for bipolar disorder with mixed states. The clinical phenotypes of bipolar disorder with mixed states vary significantly using different diagnostic tools.

Objective:This study investigates the difference in the detection rate and symptomatology between ICD-10 and DSM-5 diagnostic criteria for bipolar disorder with mixed states.Methods:Based on the Phase Ⅰ (2012) and Phase Ⅱ (2021) databases of National Bipolar Mania Pathway Survey (BIPAS), patients with bipolar disorder were included. General demographic data, clinical characteristics, symptomatic phenotypes, and mixed characteristics were retrieved. The detection rates and symptomatic performances of patients with or without mixed states in Phase Ⅰ and Ⅱ were compared using the chi-square test.Results:For patients with mixed states, the detection rate during Phase Ⅱ (2021) using DSM-5 (18.79%, 199/1 059) criteria was significantly higher than that during Phase Ⅰ (2012) using ICD-10 (6.78%, 199/2 934; χ 2=125.05, P<0.001). Whether using ICD-10 or DSM-5 criteria, patients with mixed states had a significantly higher frequency of multiple symptomatic manifestations. Conclusion:The DSM-5 diagnostic criteria generate a high detection rate for bipolar disorder with mixed states. The clinical phenotypes of bipolar disorder with mixed states vary significantly using different diagnostic tools.