Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Background/Aims: Inflammatory bowel disease (IBD) may contribute to the development of hematologic malignancies. In this study, the potential relationship between IBD and hematologic malignancies was investigated. Methods: We searched the PubMed, Web of Science, Embase, and Cochrane Library databases for all cohort studies comparing the incidence of hematologic malignancies in non-IBD populations with that in IBD patients, and we extracted relevant data from January 2000 to June 2023 for meta-analysis. Results: Twenty cohort studies involving 756,377 participants were included in this study. The results showed that compared with the non-IBD cohort, the incidence of hematologic malignancies in the IBD cohort was higher (standardized incidence ratio [SIR]=3.05, p<0.001). According to the specific types of IBD, compared with the non-IBD patients, the incidences of hematologic malignancies in ulcerative colitis patients (SIR=2.29, p=0.05) and Crohn's disease patients (SIR=3.56, p=0.005) were all higher. In the subgroup analysis of hematologic malignancy types, compared with the control group, the incidences of non-Hodgkin's lymphoma (SIR=1.70, p=0.01), Hodgkin's lymphoma (SIR=3.47, p=0.002), and leukemia (SIR=3.69, p<0.001) were all higher in the IBD cohort. Conclusions The incidence of hematologic malignancies, including non-Hodgkin's lymphoma, Hodgkin's lymphoma, and leukemia is higher in patients with IBD (ulcerative colitis or Crohn's disease) than in non-IBD patients.

Objective:To evaluate the role of bilateral superior cervical sympathetic ganglia (SCG) in myocardial ischemia-reperfusion (I/R) injury in mice and the relationship with NOD-like receptor protein 3 (NLRP3) inflammasomes.Methods:Thirty-two healthy SPF male C57BL mice, aged 8-10 weeks, weighing 25-30 g, were divided into 4 groups ( n=8 each) by the random number table method: sham operation group (NS group), myocardial I/R group (NIR group), bilateral SCG excision group (SCGx group) and bilateral SCG excision + myocardial I/R group (SCGx+ IR group). The myocardial I/R injury model was prepared by ligating the anterior descending branch of the left coronary artery for 30 min followed by 24 h reperfusion in isoflurane-anesthetized mice. Bilateral superior cervical sympathectomy was performed at 3 days before reperfusion. Blood samples were collected from the inferior vena cava at 24 h of reperfusion for examination of pathological changes (by HE and WGA staining) and for measurement of serum creatine kinase isoenzymes (CK-MB) activity, cardiac troponin I (cTnI) concentration, norepinephrine (NE) concentration and lactic dehydrogenase (LDH) activity (by enzyme-linked immunosorbent assay), superoxide dismutase (SOD) activity (by colorimetric method), myocardial reactive oxygen species (ROS) level (by DHE method), myocardial infarct size(by TTC method), and expression of interleukin-1beta (IL-1β), IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), NLRP3 mRNA (by quantitativepolymerase chain reaction ), and expression of tyrosine hydroxylase (TH), IL-1β, TNF-α, NLRP3, atrial natriuretic peptide (ANP)and brain natriuretic peptide (BNP) (by Western blot). Results:Compared with NS group, the NE concentration was significantly decreased, and TH expression was down-regulated in SCGx group, and the serum CK-MB activity, concentrations of cTnI and NE, LDH activity and myocardial ROS level were significantly increased, SOD activity was decreased, the expression of IL-1β, TNF-α, NLRP3, ANP and BNP was up-regulated, and the expression of IL-1β, IL-6, TNF-α and NLPR3 mRNA was up-regulated in NIR group ( P<0.05). Compared with SCGx group, the serum CK-MB activity, concentrations of cTnI and NE, LDH activity and myocardial ROS levels were significamtly increased, SOD activity was decreased, the expression of IL-1β, TNF-α, NLRP3, ANP and BNP was up-regulated, and the expression of IL-1β, IL-6, TNF-α and NLPR3 mRNA was up-regulated in SCGx+ NIR group ( P<0.05). Compared with NIR group, the serum CK-MB activity, cTnI concentration, LDH activity and myocardial ROS level were significantly decreased, SOD activity was increased, the expression of IL-1β, TNF-α, NLRP3, ANP and BNP was down-regulated, the expression of IL-1β, IL-6, TNF-α and NLPR3 mRNA was down-regulated, and myocardial infarct size was decreased in SCGx+ NIR group ( P<0.05). Conclusions:The mechanism by which bilateral SCG excision attenuates myocardial I/R injury is associated with decreased NLRP3 inflammatory inflammasome activation and inhibition of inflammatory responses in mice.

Malignant tumors have become one of the major diseases that seriously endanger human life.Early diagnosis and treatment can greatly improve the survival rate of patients.Imaging examinations based on fluorescence imaging,CT,photoacoustic imaging,MRI,and PET have been widely studied and applied in the diagnosis of tumors.However,early cancerous tissue and normal tissue have similar imaging signals,which is difficult to be accurately distinguished by conventional imaging.With the development and cross integration of physics,materials science,biology,and medicine,nanomaterials have shown broad application prospects in the diagnosis and treatment of diseases due to their unique physical and chemical properties.The enhanced permeability and retention effect in solid tumor,and the easy modification properties of nanomaterials allow them to accurately"recognize"tumor and accelerate its enrichment at the tumor site;the imaging characteristics allow them to be used as contrast agents to enhance the signal intensity of the tumor site;their responsiveness mechanism can also allow them to distinguish normal from cancerous cells according to the microenvironment in tumor cells.In addition,multimodality imaging based on nanomaterials can compensate for the shortcomings of single modality imaging and achieve real-time and omnidirectional imaging of tumors.With multiple functions integrated,nanomaterials are expected to enhance the imaging signals of early cancerous sites,improve signal-to-noise ratio,and achieve early diagnosis of tumors.

Objective:To evaluate the effect of verbascoside on cold ischemia-reperfusion injury following heterotopic heart transplantation in mice and the relationship with nuclear factor kappa B (NF-κB)/nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) signaling pathway.Methods:This experiment was performed in two parts. Part Ⅰ animal experiment Eighteen SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 24-28 g, were divided into 3 groups ( n=6 each) by the random number table method: control group (C group), cold ischemia-reperfusion (I/R) group (I/R group) and cold I/R + verbascoside group (I/R+ VB group). Cold I/R injury model of mouse heart transplantation was prepared by neck heterotopic heart transplantation using the modified non-suture cuff technique. The donor heart in group C was immediately transplanted to the recipient after removal, while the donor heart in group I/R was stored in the 4 ℃ University of Wisconsin solution for 8 h before transplantation to the recipient, and verbascoside 20 mg/kg was intraperitoneally injected at 3 days before surgery in donor and recipient mice in I/R+ VB group. At the end of reperfusion, the myocardial tissue of the transplanted heart was obtained after assessing the beating score for determination of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity by enzyme-linked immunosorbent assay. Part of the donor myocardium was taken for examination of the pathological results. The expression of NF-κB, p-NF-κB, NOD-like receptor protein 3 (NLRP3), ACS and caspase-1 was detected by Western blot. The expression of IL-1β, TNF-α and IL-6 mRNA was detected by real-time polymerase chain reaction. Part Ⅱ cell experiment Rat cardiomyocyte H9c2 cold hypoxia-reoxygenation model was developed, and the cells were divided into 3 groups ( n=24 each) by the random number table method: control group (C group), cold hypoxia-reoxygenation group (H/R group), and cold hypoxia-reoxygenation+ verbascoside group (H/R+ VB group). The cells were exposed to hypoxia for 18 h at 10 ℃ followed by restoration of reoxygenation for 24 h at 37 ℃ to develop the cold hypoxia-reoxygenation model. The cell viability and LDH activity were determined. The expression of NF-κB and NLRP3 was detected by Western blot, and the expression of phosphorylated NF-κB (p-NF-κB) was detected by immunofluorescence staining. Results:Part Ⅰanimal experiment Compared with C group, the MDA content was significantly increased, the beating score of grafts and SOD activity were decreased, and the expression of p-NF-κB, NLRP3, ACS and caspase-1 and IL-1β, TNF-α and IL-6 mRNA was up-regulated ( P<0.05), and myocardial histopathological injury was aggravated in I/R group. Compared with I/R group, the content of MDA was significantly decreased, the beating score of grafts and SOD activity were increased, the expression of p-NF-κB, NLRP3, ACS and caspase-1 and IL-1β, TNF-α and IL-6 mRNA was down-regulated ( P<0.05), and the myocardial histopathological injury was alleviated in I/R+ VB group. Part Ⅱ cell experiment Compared with C group, the cell viability was significantly decreased, the activity of LDH was increased, and the expression of p-NF-κB, NLRP3, ACS, caspase-1 and p-NF-κB was up-regulated in H/R group ( P<0.05). Compared with H/R group, the cell viability was significantly increased, the activity of LDH was decreased, and the expression of p-NF-κB, NLRP3, ACS, caspase-1 and p-NF-κB was down-regulated in H/R+ VB group ( P<0.05). Conclusions:Verbascoside can alleviate cold I/R injury following heterotopic heart transplantation in mice, and the mechanism may be related to inhibition of activation of NF-κB/NLRP3 signaling pathway.

Objective:To investigate the concerns of adult patients with chronic myeloid leukemia (CML) in the chronic phase receiving tyrosine kinase inhibitor (TKI) therapy in China.Methods:A cross-sectional questionnaire including 23 issues of concern was filled by patients with CML nationwide from August to September 2021. The results were compared with those from 2015 to 2016.Results:Data from 952 questionnaires were analyzed. The five most concerned issues were "TKI-related adverse effects and management" (66%) , "stopping TKI therapy" (46%) , "CML risk assessment" (46%) , "TKI dose reduction" (42%) , and "restrictions in daily life activities" (41%) . Compared with the results from 2015 to 2016, patients paid more attention to "TKI-related adverse effects and management" , "monitoring" , and "interpretation of laboratory reports" (all P<0.01) . Concerns of "TKI reimbursement policies" , "price reduction of TKIs" , and issues related to generic TKIs decreased significantly (all P<0.01) . Multivariate analysis showed that female patients ( OR=1.8, 95% CI 1.4-2.5, P<0.001) , elderly patients ( OR=1.0, 95% CI 1.0-1.0, P<0.001) , or patients with bachelor's degree or higher ( OR=1.8, 95% CI 1.3-2.4, P<0.001) were more concerned with "TKI dose reduction" than others. Patients with a bachelor’s degree or higher ( OR=1.6, 95% CI 1.2-2.2, P=0.002) paid more attention to "CML risk assessment" , whereas those currently receiving a second- or third-generation TKI therapy ( OR=1.9, 95% CI 1.3-2.6, P<0.001) were more concerned about "TKI resistance" . Conclusion:Patients with CML paid the most attention to "TKI-related adverse effects and management" , "stopping TKI therapy" , "CML risk assessment" , "TKI dose reduction" , and "restrictions in daily life activities" . Patients' sociodemographic covariates and treatment status were associated with their concerns.

Objective: To explore the relationship between insulin resistance and plasma hypersensitive reactive protein (hs-CRP) in patients with chronic schizophrenia. Methods: A total of 247 inpatients with chronic schizophrenia (patient group) and 166 cases of normal individuals(control group) were enrolled.Their general demographic and clinical data were collected, fasting blood glucose, hs-CRP, c-peptide and insulin indexes were tested, and insulin resistance index (HOMA-IR) was calculated.The insulin resistance level of the patients group and the control group was compared by Mann-Whitney U test, and the relationship between insulin-resistance and hs-CRP in patients group was analyzed using Spearman correlation analysis. Results: (1)The levels of C-peptide (2.53(2.06, 3.23)ng/ml vs 2.24(1.89, 2.87)ng/ml), insulin (7.68(4.66, 11.97)μIU/ml vs 7.02(4.31, 9.59)μIU/ml) and HOMA-IR (1.75(1.09, 3.07) vs 1.57(0.97, 2.22)) in the patient group were significantly higher than those in the control group(all P<0.05). (2) The levels of HOMA-IR( 1.91(1.21, 3.74) vs 1.70(1.02, 2.72)) in patients with high hs-CRP(≥3 mg/L) was higher than those in the patients with low hs-CRP(<3 mg/L)(P<0.05). (3)Spearman correlation analysis showed that HOMA-IR was positively correlated with plasma hs-CRP level in the patient group (r=0.139, P<0.05). (4)After logarithmic transformation of related variables, multivariate linear regression analysis showed that HOMA-IR was linearly correlated with hs-CRP level and boy weight index. Conclusion The hs-CRP level in chronic schizophrenia has a positive predictive effect on insulin resistance.Detection of hs-CRP level in schizophrenic patients is helpful to assess metabolic risk of insulin.

Objective Assessment of short?term and mid?term changes of knee cartilage in non?professional long?distance runners before and after marathon using T2 mapping imaging. Methods Twenty?four knee joints of 12 healthy volunteers (5 males and 7 females) who participated in the marathon were examined by 3.0 T MRI one week before the race, within 12 hours after the race and two months after the race, respectively. The age ranged from 21.0 to 37.0 years. Athletes run more than three times a week, and each time was about 30 minutes. From T2 mapping we can obtain T2 value of 6 cartilage subregions of knee joint. Paired t?test was used to compare the T2 values of cartilage before and after the marathon. The comparison between the superficial and deep T2 values of cartilage was performed by independent sample t test. Results T2 mapping imaging showed that the T2 value of the superficial articular cartilage was higher than that of deep articular cartilage in pre?competition, within 12 hours after competition and 2 months follow?up, respectively (t=11.095, 10.385 and 10.102, P<0.01). The T2 value of superficial articular cartilage decreased after the competition compared with that of pre?competition (t=2.18,P<0.05), while the T2 value of deep articular cartilage showed no significant difference compared with that of pre?competition (t=1.832, P> 0.05). Except for the MTP?DZ, the T2 value of the remaining cartilage subregions showed a trend of decrease within 12 hours after the competition. There were significant differences in the subregion of MFC?DZ (t=2.110,P<0.05). At the follow?up of 2 months, cartilage T2 values of the MTP?SZ,LTP?SZ,LTP?DZ,MFC?DZ, Patella?SZ, Patella?DZ, Trochlea?SZ, Trochlea?DZ subregions showed a trend of recovery, and there was no significant difference compared with pre?competition(t=0.857,0.573, 0.146, 0.510,-0.594,-1.135,-0.812,-0.679; P>0.05). The T2 values of the LFC?SZ and LFC?DZ were lower than those before the race, with statistical significance (t=2.378, 3.147,P<0.05). Conclusion T2 value could reflect the change process of articular cartilage tissue composition in marathon runners from T2 mapping imaging. Under stress, the changes of superficial T2 value are more significant. The T2 value of knee cartilage can gradually recover to the pre?run level 2 months after running.

Objective: Assessment of short-term and mid-term changes of knee cartilage in non-professional long-distance runners before and after marathon using T₂ mapping imaging. Methods: Twenty-four knee joints of 12 healthy volunteers (5 males and 7 females) who participated in the marathon were examined by 3.0 T MRI one week before the race, within 12 hours after the race and two months after the race, respectively. The age ranged from 21.0 to 37.0 years. Athletes run more than three times a week, and each time was about 30 minutes. From T₂ mapping we can obtain T₂ value of 6 cartilage subregions of knee joint. Paired t-test was used to compare the T₂ values of cartilage before and after the marathon. The comparison between the superficial and deep T₂ values of cartilage was performed by independent sample t test. Results: T₂ mapping imaging showed that the T₂ value of the superficial articular cartilage was higher than that of deep articular cartilage in pre-competition, within 12 hours after competition and 2 months follow-up, respectively (t=11.095, 10.385 and 10.102, P<0.01). The T₂ value of superficial articular cartilage decreased after the competition compared with that of pre-competition (t=2.18,P<0.05), while the T₂ value of deep articular cartilage showed no significant difference compared with that of pre-competition (t=1.832, P> 0.05). Except for the MTP-DZ, the T₂ value of the remaining cartilage subregions showed a trend of decrease within 12 hours after the competition. There were significant differences in the subregion of MFC-DZ (t=2.110,P<0.05). At the follow-up of 2 months, cartilage T₂ values of the MTP-SZ,LTP-SZ,LTP-DZ,MFC-DZ, Patella-SZ, Patella-DZ, Trochlea-SZ, Trochlea-DZ subregions showed a trend of recovery, and there was no significant difference compared with pre-competition (t=0.857,0.573, 0.146, 0.510, -0.594, -1.135, -0.812, -0.679; P>0.05). The T₂ values of the LFC-SZ and LFC-DZ were lower than those before the race, with statistical significance (t=2.378, 3.147,P<0.05). Conclusion T₂ value could reflect the change process of articular cartilage tissue composition in marathon runners from T₂ mapping imaging. Under stress, the changes of superficial T₂ value are more significant. The T₂ value of knee cartilage can gradually recover to the pre-run level 2 months after running.

MicroRNAs (miRNAs) a class of non-coding RNAs about 22 nt in size that are found in a wide range of organisms from plants, viruses to humans. MicroRNA has a wide range of biological functions. It can recruit related RNA enzymes and lead to mRNA degradation after binding to mRNA specificity, thus blocking the expression of protein encoding genes and then affecting their biological functions. In recent years, microRNA has been found to be closely related to the biological behaviors, such as the occurrence, development, invasion and metastasis of multiple human malignant carcinomas, and play a regulatory role in the above biological phenotypes. Lung cancer is the highest incidence of malignancy. The exact molecular mechanism of its occurrence and development has not been fully elucidated. Previous studies have shown that microRNA plays an important role in lung tumor suppressor gene inactivation, oncogene activation and epigenetics. At the same time, there are also reports that there is a significant difference in the expression of microRNA in patients with lung cancer and benign lung diseases. This differential expression provides a basis for the feasibility of microRNA as a diagnostic and pre biological marker for lung cancer.
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Humans ; Lung Neoplasms ; diagnosis ; genetics ; pathology ; MicroRNAs ; genetics ; Neoplasm Invasiveness ; Neoplasm Metastasis