Objective:To explore the relationship between the expression of peripheral blood interleukin-17 (IL)-17 and IL-8 and the short-term prognosis of sepsis patients.Methods:The data of 158 patients with sepsis admitted to Huzhou Central Hospital from January 2020 to January 2024 were retrospectively collected. The patient′s data were carefully reviewed, and the results of the study were recorded, including the severity of the patient′s condition (138 cases of sepsis, 20 cases of septic shock), baseline data, and short-term prognosis (28-day mortality). The levels of procalcitonin (PCT), peripheral blood IL-17, IL-8, and other laboratory indicators were compared between patients with different severity and different prognosis. COX regression model analysis and interaction test were used to verify the relationship between peripheral blood IL-17, IL-8 levels, and short-term prognosis in patients with sepsis. The receiver operating characteristic (ROC) curve was drawn and the decision curve was constructed to analyze the predictive value of peripheral blood IL-17 and IL-8 levels on the short-term prognosis of patients with sepsis.Results:The levels of IL-17 and IL-8 in the peripheral blood of patients with different severity of sepsis at admission were higher in the septic shock group than those in the sepsis group: (82.48 ± 13.54) μg/L vs. (62.84 ± 12.09) μg/L, (41.80 ± 5.46) ng/L vs. (34.22 ± 6.77) ng/L,( P<0.05). The acute physiology and chronic health evaluation (APACHE) Ⅱ score, PCT, IL-17, and IL-8 levels at admission in the death group were higher than those in the survival group, and the proportion of patients with septic shock was higher than that in the survival group: (12.09 ± 2.06) points vs. (10.81 ± 2.36) points, (2.23 ± 1.18) μg/L vs. (1.78 ± 0.69) μg/L, (79.24 ± 13.72) μg/L vs. (61.37 ± 11.15) μg/L, (42.43 ± 5.07) ng/L vs. (33.09 ± 6.14) ng/L, 51.43%(18/35) vs. 1.63%(2/123), P<0.05. COX regression analysis showed that the short-term prognosis of patients with sepsis was related to the abnormal expression of IL-17 and IL-8 in peripheral blood. The high expression of both may be a risk factor for the short-term prognosis of patients with sepsis ( P<0.05). The levels of IL-17 and IL-8 in peripheral blood had a positive interaction on the short-term prognosis of patients with sepsis. The risk of death when both were highly expressed was 97.500 times that when both were lowly expressed and the synergistic effect was 9.362 times higher than the sum of the effects produced by the two alone (synergy index = 9.362). ROC curve was drawn to obtain the area under the curve (AUC). The AUC of peripheral blood IL-17, IL-8 alone and combined to predict the short-term prognosis risk of sepsis patients were 0.839, 0.889 and 0.960, respectively, which had ideal predictive value, and the combined predictive value was higher than that of the two alone ( Z = 3.85, 2.66, P<0.05). The decision curve was drawn. When the threshold was 0.1-1.0, the net return rate of the combined prediction model of IL-17 and IL-8 in peripheral blood to predict the short-term prognosis risk of sepsis patients was better than that of IL-17 and IL-8 alone, and the maximum net return rate was 0.222. Conclusions:The more severe the condition of sepsis patients, the higher the expression of IL-17 and IL-8 in peripheral blood, which may suggest that patients have a high risk of short-term death. Early combined detection of IL-17 and IL-8 levels in the peripheral blood of sepsis patients can predict their short-term prognostic risk.

Objective:To compare knowledge graphs (KGs) constructed from standardized clinical pathways and actual examination records within 24 hours of emergency care for acute gastrointestinal hemorrhage (AGH), acute myocardial infarction (AMI), and intracerebral hemorrhage (ICH), and to visually analyze discrepancies between guideline recommendations and real-world practice, thereby exploring a novel methodology for clinical pathway optimization.Methods:KGs were developed using clinical pathway standards and actual examination data collected within the first 24 hours of emergency treatment for AGH, AMI, and ICH. Entity attributes were weighted to visually represent the frequency and extent of examination usage through variable node sizes in the KG. The constructed KGs were used to compare and analyze the differences in type and frequency of examinations performed relative to pathway standards.Results:The proportion of examination items with >50% adherence to clinical pathway standards within 24 hours was 76.92% for AGH, 44.44% for AMI, and 78.57% for ICH. Items from the clinical pathways that were not performed in over 50% of patients accounted for 15.38%, 27.78%, and 21.43% of cases, respectively. Non-pathway examinations increased by 9, 7, and 4 items for each condition, of which 17 items (85%) were performed at least once in more than half of the patients. Visualization via KGs revealed a reduction in redundant examinations by 38.64% between AGH and AMI, 35.00% between AGH and ICH, and 37.50% between AMI and ICH. Overall, a 54.84% reduction in redundant examinations was achieved across all three critical conditions.Conclusions:The visual KG approach effectively integrates both guideline-recommended and experience-driven examinations, serving as a correlational analysis tool to assess deviations between actual clinical practice and standardized pathways. It provides a quantitative foundation for optimizing clinical pathways, with potential for greater efficiency gains as more critical conditions are incorporated into the graph.

Objective:To explore the relationship between the expression of peripheral blood interleukin-17 (IL)-17 and IL-8 and the short-term prognosis of sepsis patients.Methods:The data of 158 patients with sepsis admitted to Huzhou Central Hospital from January 2020 to January 2024 were retrospectively collected. The patient′s data were carefully reviewed, and the results of the study were recorded, including the severity of the patient′s condition (138 cases of sepsis, 20 cases of septic shock), baseline data, and short-term prognosis (28-day mortality). The levels of procalcitonin (PCT), peripheral blood IL-17, IL-8, and other laboratory indicators were compared between patients with different severity and different prognosis. COX regression model analysis and interaction test were used to verify the relationship between peripheral blood IL-17, IL-8 levels, and short-term prognosis in patients with sepsis. The receiver operating characteristic (ROC) curve was drawn and the decision curve was constructed to analyze the predictive value of peripheral blood IL-17 and IL-8 levels on the short-term prognosis of patients with sepsis.Results:The levels of IL-17 and IL-8 in the peripheral blood of patients with different severity of sepsis at admission were higher in the septic shock group than those in the sepsis group: (82.48 ± 13.54) μg/L vs. (62.84 ± 12.09) μg/L, (41.80 ± 5.46) ng/L vs. (34.22 ± 6.77) ng/L,( P<0.05). The acute physiology and chronic health evaluation (APACHE) Ⅱ score, PCT, IL-17, and IL-8 levels at admission in the death group were higher than those in the survival group, and the proportion of patients with septic shock was higher than that in the survival group: (12.09 ± 2.06) points vs. (10.81 ± 2.36) points, (2.23 ± 1.18) μg/L vs. (1.78 ± 0.69) μg/L, (79.24 ± 13.72) μg/L vs. (61.37 ± 11.15) μg/L, (42.43 ± 5.07) ng/L vs. (33.09 ± 6.14) ng/L, 51.43%(18/35) vs. 1.63%(2/123), P<0.05. COX regression analysis showed that the short-term prognosis of patients with sepsis was related to the abnormal expression of IL-17 and IL-8 in peripheral blood. The high expression of both may be a risk factor for the short-term prognosis of patients with sepsis ( P<0.05). The levels of IL-17 and IL-8 in peripheral blood had a positive interaction on the short-term prognosis of patients with sepsis. The risk of death when both were highly expressed was 97.500 times that when both were lowly expressed and the synergistic effect was 9.362 times higher than the sum of the effects produced by the two alone (synergy index = 9.362). ROC curve was drawn to obtain the area under the curve (AUC). The AUC of peripheral blood IL-17, IL-8 alone and combined to predict the short-term prognosis risk of sepsis patients were 0.839, 0.889 and 0.960, respectively, which had ideal predictive value, and the combined predictive value was higher than that of the two alone ( Z = 3.85, 2.66, P<0.05). The decision curve was drawn. When the threshold was 0.1-1.0, the net return rate of the combined prediction model of IL-17 and IL-8 in peripheral blood to predict the short-term prognosis risk of sepsis patients was better than that of IL-17 and IL-8 alone, and the maximum net return rate was 0.222. Conclusions:The more severe the condition of sepsis patients, the higher the expression of IL-17 and IL-8 in peripheral blood, which may suggest that patients have a high risk of short-term death. Early combined detection of IL-17 and IL-8 levels in the peripheral blood of sepsis patients can predict their short-term prognostic risk.

Objective:To investigate the clinical efficacy of daratumumab-containing regimen in the treatment of multiple myeloma (MM) and the associated factors affecting patients' progression-free survival (PFS).Methods:A retrospective case series study was conducted. Clinical data of 21 MM patients who were treated with daratumumab-containing regimen in the Heping Hospital Affiliated to Changzhi Medical College from January 2021 to September 2023 were collected. The patients were treated with daratumumab (16 mg/kg intravenous drip) combined with other drugs for 28 d as 1 cycle until disease progression. Among the 21 cases, 6 cases were newly diagnosed multiple myeloma (NDMM), 7 cases were relapsed/refractory multiple myeloma (RRMM), and 8 cases were second-line treatment with daratumumab after the poor outcome of VRD (bortezomib + lenalidomide +dexamethasone) regimen at the time of initial treatment (daratumumab second-line treatment group). The efficacy of the patients after 2 cycles of daratumumab treatment was summarized; the PFS of the whole group and the NDMM and RRMM patients was analyzed by using Kaplan-Meier method, and log-rank test was used for comparison between the groups; the different status of disease, gender and age were included in the univariate and multivariate Cox proportional hazards models to screen the factors affecting the PFS of MM patients.Results:The median age [ M ( Q1, Q3)] of 21 patients was 62 years old (55 years old, 68 years old); 17 were male and 4 were female. After 2 cycles of daratumumab treatment, the overall remission rate (ORR) of the whole group was 85.7% (18/21), 2 cases (9.5%) achieved strict complete remission (sCR), 3 cases (14.3%) achieved complete remission (CR), 9 cases (42.9%) achieved very good partial remission (VGPR), 4 cases (19.0%) achieved partial remission (PR), 2 cases (9.5%) had stable disease and 1 case (4.8%) had disease progression. After 2 cycles of daratumumab treatment, all 6 NDMM patients were in remission, with 2 cases of sCR, 1 case of CR, and 3 cases of VGPR; 4 of 7 RRMM patients were in remission, with 1 case of CR and 3 cases of PR; 8 patients with daratumumab second-line treatment were in remission, with 1 case of CR, 6 cases of VGPR, and 1 case of PR; the difference in ORR among the 3 groups was statistically significant ( P = 0.010), the difference in ORR between patients with NDMM and daratumumab second-line treatment was not statistically significant ( P = 0.245), the ORR of NDMM patients was higher than that of RRMM patients, and the difference was statistically significant ( P = 0.029). The median follow-up time was 15.4 months (95% CI: 13.7-17.1 months). The median PFS time for the whole group was 10.6 months (95% CI: 7.3-15.5 months); the median PFS time was not reached in NDMM patients, the median PFS time was 14.6 months (95% CI: 2.1-27.2 months) in RRMM patients, the median PFS time was 9.6 months (95% CI: 9.5-9.7 months) in patients with daratumumab second-line treatment, and the difference in PFS among the 3 groups was not statistically significant ( P = 0.085). Multivariate Cox regression analysis showed that high age was an independent risk factor for PFS in MM patients ( HR = 1.12, 95% CI: 1.03-1.21, P = 0.009). Conclusions:Daratumumab has good results in treating MM and can be used as a first-line treatment option for NDMM patients, which may improve the remission rate of MM patients with previous ineffective treatment of VRD regimen, and may also improve the prognosis of RRMM patients. High age may be a risk factor for disease progression in MM patients treated with daratumumab.

A 62-year-old male patient with chronic myelogenous leukemia (chronic phase) received nilotinib 400 mg twice daily. The patient developed mild fatigue, precordial discomfort, and chest tightness 5 hours after the first medication, which were relieved after rest. One hour after the second medication on the same day, the symptoms of precordial discomfort and chest tightness recurred, and they were relieved after rest again. One hour after taking the medicine again the next day, the above symptoms recurred and were aggravated, which could not be relieved after rest. Laboratory tests showed that serum troponin I was 2.67 μg/L, myoglobin was 195.1 μg/L, and creatine kinase MB was 37.7 μg/L. Electrocardiogram (ECG) showed that ST segment depression was >0.1 mV in leads I, II, III, aVL, aVF, and V 1-V 6, T-wave inversion, and QT/QTc was 350/402 ms. The patient was diagnosed as having acute non-ST segment elevation myocardial infarction, which was considered to be related to nilotinib. After 3 weeks of drug withdrawal and vasodilator and anticoagulant therapy, the laboratory tests showed that serum troponin I was not detected, myoglobin was 21.7 μg/L, and creatine kinase MB was 0.8 μg/L. ECG examination showed ST segment depression and T-wave inversion disappeared in leads I, II, III, aVL, aVF and V 1-V 6, and QT/QTc was 370/376ms.

A 62-year-old male patient with chronic myelogenous leukemia (chronic phase) received nilotinib 400 mg twice daily. The patient developed mild fatigue, precordial discomfort, and chest tightness 5 hours after the first medication, which were relieved after rest. One hour after the second medication on the same day, the symptoms of precordial discomfort and chest tightness recurred, and they were relieved after rest again. One hour after taking the medicine again the next day, the above symptoms recurred and were aggravated, which could not be relieved after rest. Laboratory tests showed that serum troponin I was 2.67 μg/L, myoglobin was 195.1 μg/L, and creatine kinase MB was 37.7 μg/L. Electrocardiogram (ECG) showed that ST segment depression was >0.1 mV in leads I, II, III, aVL, aVF, and V 1-V 6, T-wave inversion, and QT/QTc was 350/402 ms. The patient was diagnosed as having acute non-ST segment elevation myocardial infarction, which was considered to be related to nilotinib. After 3 weeks of drug withdrawal and vasodilator and anticoagulant therapy, the laboratory tests showed that serum troponin I was not detected, myoglobin was 21.7 μg/L, and creatine kinase MB was 0.8 μg/L. ECG examination showed ST segment depression and T-wave inversion disappeared in leads I, II, III, aVL, aVF and V 1-V 6, and QT/QTc was 370/376ms.

Objective: To investigate the value of NPM1 and FLT3 gene mutation combined with bone marrow imaging detection in the prognosis judgement of initial treatment cytogenetically normal acute myeloid leukemia (CN-AML). Methods: The clinical data of 100 patients (non-M₃ type) with primary and initial treatment CN-AML from January 2010 to January 2014 in the Peace Hospital Affiliated of Changzhi Medical College were retrospectively analyzed. All patients were enrolled in the bone marrow imaging examination on the end day of induction treatment or the first day after the end of induction treatment (T time point). Univariate and multivariate prognostic analyses were performed on AML patients according to FLT3 and NPM1 gene status,bone marrow juvenile cell ratio at T time point. Results: A total of 100 patients included 36 cases with FLT3 gene mutation and 44 cases with NPM1 gene mutation. The complete remission (CR) rate of CN-AML patients was 13.9% (5/36) and 71.9% (46/64), respectively (P < 0.01), 2-year recurrence-free survival (RFS) rate was 5.6% and 59.8%, respectively (P < 0.01), 2-year overall survival (OS) rate was 15.6% and 66.2%, respectively in FLT3⁺ group and FLT3^- group (P < 0.01). The median RFS and median OS time in FLT3⁺ group was 6.9 months and 9.4 months, respectively, and the median RFS and median OS time in FLT3^- group had not yet reached. There were no significant differences of all the indexes between the two groups (all P < 0.01). And there were no significant differences in CR rate, 2-year RFS rate and 2-year OS rate between NPM1⁺ group and NPM1^- group (all P > 0.05). The CR rate, 2-year RFS rate and 2-year OS rate in NPM1⁺ FLT3^- group were better than those in NPM1^- FLT3^-, NPM1^- FLT3⁺ and NPM1⁺ FLT3⁺ groups; NPM1^- FLT3⁺ and NPM1⁺ FLT3⁺ groups had the worst prognosis, and there were no statistical differences in the CR rate, RFS and OS time between the two groups (all P > 0.05). The prognosis of the patients in bone marrow juvenile cell ratio < 0.05 group at T time point was better than that in ratio ≥0.05 group (all P < 0.05). CN-AML patients were classified into the good prognosis group (NPM1^- FLT3^-), the medium prognosis group (NPM1⁺ FLT3^-), and the poor prognosis group (NPM1^- FLT3⁺ and NPM1⁺ FLT3⁺) according to the FLT3 and NPM1 genes. The good prognosis group+ the ratio of bone marrow juvenile cells at T time point < 0.05 group, the good prognosis group+ the ratio of bone marrow juvenile cells at T time point ≥0.05 group, the medium prognosis group+ the ratio of bone marrow juvenile cells at T time point < 0.05 group had no statistical differences in CR rate, 2-year RFS rate and 2-year OS rate (all P > 0.05). The medium prognosis group+ the ratio of bone marrow juvenile cells at T time point ≥0.05 group, the poor prognosis group+ the ratio of bone marrow juvenile cells at T time point < 0.05 group had the equivalent prognosis, and the average prognosis was moderate; the poor prognosis group+ the ratio of bone marrow juvenile cells at T time point ≥ 0.05 group had the worst prognosis. According to Cox multivariate regression analysis, FLT3 gene mutation and the ratio of bone marrow juvenile cells at T time point were independent influencing factors for RFS and OS in CN-AML patients (all P < 0.05). NPM1 was an independent prognosis factor affecting RFS and OS of FLT3^- patients (all P < 0.05). Conclusions After induction chemotherapy, the responsiveness and sensitivity of AML patients to chemotherapy regimen can be assessed early and objectively according to molecular genetics and the ratio of bone marrow juvenile cells at T time point, which has a certain value in the prognosis judgement.

Acquired aplastic anemia(AA) is a disease of bone marrow failure mediated by autoimmune T cells. CD4+CD25+ regulatory T cells, which have immunosuppressive and anergic, belong to a subpopulation of T cells specialized for immune regulation and play important roles in the development of autoimmune T cells. Foxp3 plays a significant role in the development and function of regulatory T cells which have been confirmed by many investigations. In recent years, the relationship between CD4 +CD25 +Foxp3 + regulatory T cells and AA has become a hot spot of research. What’s more, its clinical significance is becoming more and more obvious in AA.

OBJECTIVETo detect the activity of autophagy and explore the impact on survival and proliferation of HEL cells and hematopoietic cells of polycythemia vera （PV） patients with JAK2 V617F mutation.

METHODSFlow cytometry, AO staining and Western blot methods were used to detect the autophagy activity and the expression of LC3-Ⅱ protein of JAK2 V617F+ HEL cells and hematopoietic cells of 12 newly diagnosed PV patients with JAK2 V617F mutation. HEL cells and bone marrow cells of 3 PV patients were treated with rapamycin or 3-MA to induce and inhibit autophagy, respectively. CellTiter Glo(R) method was used to detect the proliferation activity of cells.

RESULTSThere was higher level of mean LC3-Ⅱ fluorescence intensity in HEL cells (159 389 ± 29 001) than that in K562 cells (96 047 ± 24 134) (P=0.044). The formation of autophagosome in HEL cells is more than that in K562 cells detected by microscope. What's more, the level of mean LC3-Ⅱ fluorescence intensity in 12 PV patients' myeloid cells (92 842 ± 4 250) was higher than that of 15 healthy volunteers (86 633 ± 2 504) (P=0.001). The expression of LC3-Ⅱ protein was higher in PV patients' peripheral blood cells than that in healthy volunteers detected by Western blot. After treated with rapamycin 12, 24, 48 h, the activity of autophagy in HEL cells and bone marrow cells of 3 PV patients were increased and the proliferation activity was higher than the control group, the proliferation activity at 48 h were (101 413 ± 3 720), (18 744 ± 1 015), respectively. However, after treated with 3-MA 12, 24, 48 h, the activity of autophagy was decreased and the proliferation activity was lower than the control group, the proliferation activity at 48 h were (5 732 ± 166), (5 371 ± 56), respectively.

CONCLUSIONThere is high basical activity of autophagy in JAK2 V617F+ HEL cells and hematopoietic cells of PV patients with JAK2 V617F mutation. Up-regulated autophagy promotes proliferation of JAK2 V617F⁺ HEL cells and bone marrow cells of PV patients with JAK2 V617F mutation. Decreased autophagy inhibits proliferation of JAK2 V617F+ HEL cells and bone marrow cells of PV patients with JAK2 V617F mutation.

Objective To investigate the proliferation inhibition and the apoptosis induction effect of brucine on human chronic myeloid leukemia cell line HL-60 cells.Methods HL-60 cells were exposed to various dosages of brucine 24,48,72 h respectively,MTT method was used to assay the growth inhibition effect of brucine on HL-60 cells and the IC50 of brucine was evaluated at the same time.The morphology was observed by AO/EB stains.The cell apoptosis and cell cycle was tested by flow cytometry with Annexin V-FITC/PI double staining and PI labeling respectively.Results The results indicated that the brucine displayed significant anti-proliferative effect on HL-60 cells in a dose-and time-dependent manner,with IC50 value of 211.8 μg/ml(24 h),107 μg/ml(48 h),83 μg/ml(72 h)respectively.The most significant inhibition was observed at 320 μg/ml for 48 h.In this condition,apoptosis morphology was induced by brucine with nuclear chromatin condensation,most of the nuclears were orange stained and condensation-like or bead-like,which was consistent with the Annexin V-FITC/PI results.The cell apoptosis rates were(2.1±1.1)％,(21.3±1.2)％,(38.6±1.3)％,(58.5±4.1)％,(75.3±0.87)％and(66.2±0.75)％in different dose of brucine,respectively.At the same time,the cell cycle analysis results showed that the cell ratio in G0/G1 phase was decreased while in G2/M and sub-G0 phases was increased,comparing with blank control group.Conclusion Brucine can inhibit cell growth dramatically,which may be related to the cell apoptosis and the cell cycle arrest.