OBJECTIVE: To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene. METHODS: From May 2017 to October 2023， among 2 113 AML patients who visited the Hematology Department of our hospital, patients with NUP98 rearrangements were screened. The clinical characteristics, chromosome karyotypes, immunophenotypes, gene mutations, treatment efficacy and prognosis of the patients with NUP98::HOXA9 positive were analyzed. RESULTS: Among the 2 113 AML patients, there were 18 cases with NUP98 rearrangement, including 14 NUP98::HOXA9 positive cases, with a detection rate of 0.66% (14/2 113). The median age of the NUP98::HOXA9 positive patients was 42.5 (23-64) years old. The most common chromosome karyotype was t(7; 11)(p15; p15). The immunophenotypes of all patients expressed CD13, CD33, CD117 and CD38, and most patients expressed CD34 and cMPO, while only a few expressed HLA-DR. Second-generation sequencing (NGS) was performed to detect genetic mutations associated with leukemia in all 14 patients, and the genes exhibiting a high frequency of mutation were WT1 (10/14), TET2 (7/14), and FLT3-ITD (6/14). Additionally, mutations were also observed in KRAS/NRAS, IDH1, and KIT. Of the 13 patients who received treatment, 9 achieved complete remission (CR), and all 3 patients who received azacytidine(AZA)+ venetoclax (VEN) regimen achieved CR after the first course of treatment. Within this cohort, 6 patients were classified as relapsed/refractory (6/13). 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which two achieved long-term survival. The median follow-up time was 12 (2.1-65.0) months, while the median overall survival (OS) and relapse-free survival (RFS) were recorded as 11.4 months and 9.6 months, respectively. CONCLUSION The most common type of NUP98 rearrangement in adults AML patients is NUP98::HOXA9 , which is often accompanied by somatic mutations in WT1, TET2, and FLT3-ITD. These patients are prone to relapse, have short survival time, and generally face poor prognoses. Hopefully, utilization of the AZA+VEN regimen is anticipated to enhance the rate of induced remission in the patients, and some patients may prolong their survival through allo-HSCT. However, more effective treatment methods are still needed to improve the overall prognosis of these patients.
Humans ; Adult ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Prognosis ; Nuclear Pore Complex Proteins/genetics* ; Oncogene Proteins, Fusion/genetics* ; Mutation ; Male ; Female ; Young Adult ; Homeodomain Proteins/genetics*

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates gene expression in a range of cells, including immune and epithelial cells. AhR signaling plays important roles in the immune system in both health and disease states. Tapinarof is a first-in-class small-molecule topical therapeutic AhR modulating agent launched for the treatment of psoriasis. To improve the activity and chemical stability of Tapinarof, a series of 2-phenylchromen-4-one derivatives were designed, synthesized and evaluated as novel AhR agonists. Compounds 5a, 5c, 5e and 5f potently activated AhR with an EC₅₀ value of 7, 9, 6 and 6 nmol·L^-1, respectively, which are 10-14 fold more potent than Tapinarof. Compounds 5a and 5e exhibit comparable inhibitory effects on IFN-γ production as Tapinarof. Furthermore, compounds 5a-5f exhibited favorable photochemical stability compared to Tapinarof. The compounds may eventually serve as lead compounds for the development of new AhR agonists.

Objective To observe the application effect of intra-arterial tirofiban during mechanical thrombectomy for acute anterior circulation cerebral infarction.Methods The clinical data of patients with acute anterior circulation cerebral infarction were retrospectively analyzed.According to cohort method,they were divided into control group and treatment group.The control group was treated with mechanical thrombectomy,while the treatment group was additionally given intra-arterial therapy with tirofiban 0.25-0.5 mg on the basis of the control group.The perioperative indicators(surgical time,number of thrombectomy,vascular recanalization time,vascular recanalization rate),National Institutes of Health Stroke Scale(NIHSS)score before treatment and at 24 hours and 7 days after treatment,platelet indicators[mean platelet distribution width(PDW),mean platelet volume(MPV),plateletcrit(PCT)],hemorheological indicators[plasma viscosity(PV),low whole blood viscosity(LWBV),high whole blood viscosity(HWBV)],serum indicators[high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),vascular endothelial growth factor(VEGF)]and clinical efficacy were compared,and the safety of the treatment regimen was assessed.Results There were 92 patients were finally included in this study,including 49 cases in control group and 43 cases in treatment group.The effective rates in treatment group and control group were 75.51％(37 cases/49 cases)and 93.02％(40 cases/43 cases),with significant difference(P＜0.05).The surgical times in treatment group and control group were(93.53±9.86)and(91.59±8.36)min;the vascular recanalization times were(78.46±9.69)and(77.40±10.32)min;the vascular recanalization rates were 93.02％and 83.67％;the NIHSS scores were(10.32±2.90)and(9.59±2.84)points at 24 hours after treatment,all with no significant difference(all P＞0.05).At 7 days after treatment,the NIHSS scores in treatment group and control group were(3.34±1.25)and(4.12±1.48)points;the PDW values were(12.58±1.81)％and(14.15±1.95)％;MPV values were(9.16±1.24)and(11.26±1.86)fL;PCT levels were(0.33±0.05)％and(0.29±0.04)％;PV values were(1.64±0.27)and(1.99±0.24)mPa·s-1;LWBV values were(4.16±0.48)and(5.01±0.49)mPa·s-1;HWBV values were(8.12±0.54)and(9.27±0.68)mPa·s-1;serum hs-CRP levels were(3.57±0.45)and(4.48±0.83)mg·L-1;TNF-α levels were(20.42±4.55)and(27.34±4.95)ng·L-1;VEGF levels were(738.80±52.41)and(664.72±41.68)ng·L-1,all with significant difference(all P＜0.05).Incidence rates of adverse drug reactions in treatment group and control group were 8.16％(4 cases/49 cases)and 4.65％(2 cases/43 cases)respectively,with no significant difference(P＞0.05).Conclusion Intra-arterial tirofiban therapy during thrombectomy for acute anterior circulation cerebral infarction has good neurological function and prognosis,and it may be related to the improvement of platelet function and cerebral tissue blood flow and relief of inflammatory response.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

OBJECTIVE: To observe the therapeutic effects and underlying mechanism of baicalin against colon cancer. METHODS: The effects of baicalin on the proliferation and growth of colon cancer cells MC38 and CT26. WT were observed and predicted potential molecular targets of baicalin for colon cancer therapy were studied by network pharmacology. Furthermore, molecular docking and drug affinity responsive target stability (DARTS) analysis were performed to confirm the interaction between potential targets and baicalin. Finally, the mechanisms predicted by in silico analyses were experimentally verified in-vitro and in-vivo. RESULTS: Baicalin significantly inhibited proliferation, invasion, migration, and induced apoptosis in MC38 and CT26 cells (all P<0.01). Additionally, baicalin caused cell cycle arrest at the S phase, while the G₀/G₁ phase was detected in the tiny portion of the cells. Subsequent network pharmacology analysis identified 6 therapeutic targets associated with baicalin, which potentially affect various pathways including 39 biological processes and 99 signaling pathways. In addition, molecular docking and DARTS predicted the potential binding of baicalin with cyclin dependent kinase inhibitor 2A (CDKN2A), protein kinase B (AKT), caspase 3, and mitogen-activated protein kinase (MAPK). In vitro, the expressions of CDKN2A, MAPK, and p-AKT were suppressed by baicalin in MC38 and CT26 cells. In vivo, baicalin significantly reduced the tumor size and weight (all P<0.01) in the colon cancer mouse model via inactivating p-AKT, CDKN2A, cyclin dependent kinase 4, cyclin dependent kinase 2, interleukin-1, tumor necrosis factor α, and activating caspase 3 and mouse double minute 2 homolog signaling (all P<0.05). CONCLUSION Baicalin suppressed the CDKN2A protein level to prevent colon cancer and could be used as a therapeutic target for colon cancer.
Flavonoids/pharmacology* ; Colonic Neoplasms/prevention & control* ; Animals ; Cell Line, Tumor ; Molecular Docking Simulation ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Cyclin-Dependent Kinase Inhibitor p16/metabolism* ; Mice ; Mice, Inbred BALB C ; Cell Movement/drug effects* ; Humans ; Gene Expression Regulation, Neoplastic/drug effects* ; Cell Cycle Checkpoints/drug effects*

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.
Humans ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Treatment Outcome

Cardiovascular disease (CVD) is an important factor threatening the health of the elderly. Aging leads to changes in the structure and function of the cardiovascular system, which increases the risk of CVD in the elderly. Cardiac aging is characterized by increased left ventricular wall thickness, increased degree of myocardial fibrosis, increased cardiac hardness, and decreased cardiac function, while vascular aging is characterized by enlarged lumen, thickened wall, and endothelial dysfunction. Promoting healthy cardiovascular aging means reducing the age-related cardiovascular dysfunction and the risks of CVD. Exercise is a crucial means for the treatment and rehabilitation of CVD. Exercise reduces the risk factors of CVD, remodels the cardiovascular structure, and increases the resistance of heart to detrimental stimulus, which promotes healthy cardiovascular aging. The improved mitochondrial function via exercise plays a key role in the health effects of exercise. In addition, exercise promotes the secretion of exerkines in various tissues and organs, which plays a role in reducing inflammation, improving metabolism, inhibiting apoptosis, etc., thus benefiting cardiovascular health. This review discusses the mechanism and potential application of exercise in promoting healthy cardiovascular aging. Exploring the specific mechanisms underlying exercise-induced cardiovascular health and formulating accurate exercise prescriptions for different populations is an important direction to promote healthy cardiovascular aging and prevent CVD.
Humans ; Aged ; Heart ; Exercise ; Aging ; Cardiovascular Diseases/prevention & control* ; Risk Factors

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

OBJECTIVE: To investigate whether Omicron BA.1 breakthrough infection after receiving the SARS-CoV-2 vaccine could create a strong immunity barrier. METHODS: Blood samples were collected at two different time points from 124 Omicron BA.1 breakthrough infected patients and 124 controls matched for age, gender, and vaccination profile. Live virus-neutralizing antibodies against five SARS-CoV-2 variants, including WT, Gamma, Beta, Delta, and Omicron BA.1, and T-lymphocyte lymphocyte counts in both groups were measured and statistically analyzed. RESULTS: The neutralizing antibody titers against five different variants of SARS-CoV-2 were significantly increased in the vaccinated population infected with the Omicron BA.1 variant at 3 months after infection, but mainly increased the antibody level against the WT strain, and the antibody against the Omicron strain was the lowest. The neutralizing antibody level decreased rapidly 6 months after infection. The T-lymphocyte cell counts of patients with mild and moderate disease recovered at 3 months and completely returned to the normal state at 6 months. CONCLUSION Omicron BA.1 breakthrough infection mainly evoked humoral immune memory in the original strain after vaccination and hardly produced neutralizing antibodies specific to Omicron BA.1. Neutralizing antibodies against the different strains declined rapidly and showed features similar to those of influenza. Thus, T-lymphocytes may play an important role in recovery.
Humans ; Antibodies, Neutralizing ; Prospective Studies ; SARS-CoV-2 ; Breakthrough Infections ; COVID-19 Vaccines ; COVID-19 ; T-Lymphocytes ; China/epidemiology* ; Antibodies, Viral

Objective To investigate the impact of microvascular obstruction (MVO) on the global and regional myocardial function by cardiac magnetic resonance feature-tracking (CMR-FT) in ST-segment-elevation myocardial infarction (STEMI) patients after percutaneous coronary intervention.Methods Consecutive acute STEMI patients who underwent cardiac magnetic resonance imaging 1 - 7 days after successful reperfusion by percutaneous coronary intervention treatment were included in this retrospective study. Based on the presence or absence of MVO on late gadolinium enhancement images, patients were divided into groups with MVO and without MVO. The infarct zone, adjacent zone, and remote zone were determined based on a myocardial 16-segment model. The radial strain (RS), circumferential strain (CS), and longitudinal strain (LS) of the global left ventricle (LV) and the infarct, adjacent, and remote zones were measured by CMR-FT from cine images and compared between patients with and without MVO using independent-samples t-test. Logistic regression analysis was used to assess the association of MVO with the impaired LV function.Results A total of 157 STEMI patients (mean age 56.66 ± 11.38 years) were enrolled. MVO was detected in 37.58% (59/157) of STEMI patients, and the mean size of MVO was 3.00 ±3.76 mL. Compared with patients without MVO (n =98 ), the MVO group had significantly reduced LV global RS (t= -4.30, P < 0.001), global CS (t= 4.99, P < 0.001), and global LS ( t= 3.51, P = 0.001). The RS and CS of the infarct zone in patients with MVO were significantly reduced (t= -3.38, P = 0.001; t= 2.64, P = 0.01; respectively) and the infarct size was significantly larger (t= 8.37, P < 0.001) than that of patients without MVO. The presence of LV MVO [OR= 4.10, 95%CI: 2.05 - 8.19, P<0.001) and its size [OR=1.38, 95%CI: 1.10-1.72, P=0.01], along with the heart rate and LV infarct size were significantly associated with impaired LV global CS in univariable Logistic regression analysis, while only heart rate (OR=1.08, 95%CI: 1.03 - 1.13, P=0.001) and LV infarct size (OR=1.10, 95%CI: 1.03 - 1.16, P=0.003) were independent influencing factors for the impaired LV global CS in multivariable Logistic regression analysis.Conclusion The infarct size was larger in STEMI patients with MVO, and MVO deteriorates the global and regional LV myocardial function.
Humans ; Middle Aged ; Aged ; ST Elevation Myocardial Infarction/complications* ; Contrast Media ; Retrospective Studies ; Gadolinium ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Percutaneous Coronary Intervention