The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Microspheres (MS) are an excellent transarterial chemoembolization carrier for cancer treatment. Then the Bletilla striata polysaccharide (BSP) that was isolated from the rattan of Bletilla striata was used as skeleton material, and the matrine (ME) loaded Bletilla striata polysaccharide microspheres (ME-BSPMS) were prepared by emulsify-chemical crosslinking method. ME-BSPMS was characterized for appearance shape, particle size, drug loading, swelling ratio, suspension property, drug entrapment condition and in vitro release characteristics. The results showed that the ME-BSPMS appeared as round spherical and smooth shape by SEM, with an average size of (85 ±7) μm. ME-BSPMS with a good suspension in physiological saline and the swelling ratio could reach upwards of (53 ±4.2)% in 20 minutes, also with a large amount of drug loading of (30.12 ±3.25)%. The results of DSC scanning indicate that good compatibility exists between the ME and BSP, and the ME could be embedded fully in the matrix of the ME-BSPMS. The accumulation drug release from ME-BSPMS was (25.38 ±1.57)% at 12 h, this suggests that the ME-BSPMS has a good sustained release effect. These results indicate that the ME-BSPMS may be a promising transarterial chemoembolization carrier for cancer treatment.

Objective To study the optimal waist circumference (WC) cut-off values for identifying metabolic risk factors in middle-aged and elderly subjects in Shandong Province of China.
Methods A total of 2 873 men and 5 559 women were included in this cross-sectional study. Metabolic syndrome (MetS) was diagnosed according to the definition of Chinese Diabetes Society in 2004. The relation between WC and MetS was analyzed by multivariate logistic regression analysis. The optimal WC cut-off values were identified using the area under the ROC curve and the different diagnostic criteria for central obesity were compared.
Results The WC was the risk factor for MetS independent of BMI, blood glucose, blood lipid, and blood pressure. The optimal WC cut-off value was 83.8 cm and 91.1 cm for identifying MetS in women and men, respectively. Compared with 80 cm and 85 cm for women and men, 85 cm and 90 cm had a higher Youden index for identifying all metabolic risk factors and MetS in women and men.
Conclusion The appropriate WC cut-off value is 85 cm and 90 cm for identifying central obesity and MetS in women and men in Shandong Province of China.

OBJECTIVETo compare the short-term outcomes of surgical treatment for non-small cell lung cancer (NSCLC) by video-assisted thoracoscopic surgery (VATS) and open thoracotomy (OT).

METHODSData of 737 consecutive NSCLC patients who underwent surgical treatment for non-small cell lung cancer by video-assisted thoracoscopic surgery and 630 patients who underwent pulmonary resection via open thoracotomy (as controls) in Cancer Institute & Hospital, Chinese Academy of Medical Sciences between January 2009 and August 2011 were retrospectively reviewed. The risk factors after lobectomy were also analyzed.

RESULTSIn the 506 NSCLC patients who received VATS lobectomy, postoperative complications occurred in 13 patients (2.6%) and one patient died of acute respiratory distress syndrome (0.2%). In the 521 patients who received open thoracotomy (OT) lobectomy, postoperative complications occurred in 21 patients (4.0%) and one patient died of pulmonary infection (0.2%). There was no significant difference in the morbidity rate (P > 0.05) and mortality rate (P > 0.05) between the VATS group and OT group. In the 190 patients who received VATS wedge resections, postoperative complications occurred in 3 patients (1.6%). One hundred and nine patients received OT wedge resections. Postoperative complications occurred in 4 patients (3.7%). There were no significant differences for morbidity rate (P = 0.262) between these two groups, and there was no perioperative death in these two groups. Univariate and multivariate analyses demonstrated that age (OR = 1.047, 95%CI: 1.004 - 1.091), history of smoking (OR = 6.374, 95%CI: 2.588 - 15.695) and operation time (OR = 1.418, 95%CI: 1.075 - 1.871) were independent risk factors of postoperative complications.

CONCLUSIONSTo compare with the NSCLC patients who should undergo lobectomy or wedge resection via open thoracotomy, a similar short-term outcome can be achieved via VATS approach.

Age Factors ; Carcinoma, Non-Small-Cell Lung ; mortality ; pathology ; surgery ; Female ; Humans ; Length of Stay ; Lung Neoplasms ; mortality ; pathology ; surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Operative Time ; Pneumonectomy ; adverse effects ; classification ; methods ; Postoperative Complications ; etiology ; Respiratory Distress Syndrome, Adult ; etiology ; Retrospective Studies ; Smoking ; Thoracic Surgery, Video-Assisted ; adverse effects ; Thoracotomy ; adverse effects ; methods

OBJECTIVETo study the epileptiform discharges and sleep structure in children with nocturnal epilepsy.

METHODSA total of 54 children with nocturnal epilepsy (NE group) between December 2009 and June 2011 were enrolled in this study using a cluster sampling method. Their epileptiform discharges and sleep structure were monitored using nocturnal 12 h-video-echoencephalography (EEG) and polysomnography. Meanwhile, 40 age- and gender-matched normal children were enrolled as the control group.

RESULTSAll the 54 children in the NE group suffered from epileptiform discharges and a varied number of clinical seizures, especially at S1 and S2 states. Compared with the control group, S1 and S2 states had significantly higher proportions in the NE group, and S3 and S4 states and REM state had significantly lower proportions (P<0.01).

CONCLUSIONSEpileptiform discharges and clinical seizures are more common in children with nocturnal epilepsy, especially during the non-rapid eye movement sleep. Meanwhile, remarkably disordered sleep structure also exists.

Child ; Child, Preschool ; Electroencephalography ; Epilepsy ; physiopathology ; Female ; Humans ; Male ; Polysomnography ; Sleep ; physiology

Objective To analyze the risk factors related to in-hospital bleeding for patients with acute coronary syndrome (ACS).Methods Clinical and therapeutic data of 3807 patients who were registered with acute coronary syndrome in SINO-GRACE in China from March 2001 to December 2007 were reviewed.A total of 57 patients were grouped to bleeding group and 234 out of the remaining 3750 patients without bleeding were randomly chosen and served as non-bleeding group.Hemorrhage-related factors were screened and compared between the two groups.Unitary logistic regression analysis was performed to detect the possible factors related to hemorrhage.Factors with P ＜ 0.1 were further analyzed by stepwise regression method and multivariate conditional logistic regression analyses.Results (1) Age,history of coronary artery bypass graft (CABG),previous hemorrhage,renal failure and heart failure as well incidence of acute coronary syndrome were significantly higher in bleeding group than in non-bleeding group (all P ≤0.05).Patients were more often treated with clopidogrel and glycoprotein (GP) Ⅱ b/Ⅲ a receptor antagonist in bleeding group than in non-bleeding group.(2) Single factor logistic regression analysis showed that age ＞70 years,history of previous bleeding,renal failure,heart failure,clopidogrel and GP Ⅱ b/Ⅲ a receptor antagonists use,non-ST-segment elevation myocardial infarction,inferior wall,lateral myocardial infarction,CABG were risk factors for bleeding (all P ＜ 0.05).(3) Multivariate logistic regression analysis showed that history of renal failure (OR =19.77,95％ CI 4.38-89.18,P ＜ 0.01) and clopidogrel (OR =19.77,95％ CI 4.38-89.18,P ＜ 0.01) and GP Ⅱ b/Ⅲ a receptor antagonist (OR =343.57,95％ CI 40.39-999.99,P ＜ 0.01) use were the independent risk factors for bleeding.Conclusion Our results show that renal failure history and clopidogrel and GP Ⅱ b/Ⅲ a receptor antagonist use are independent risk factors for in-hospital bleeding in patients with acute coronary syndrome.

Objective To assess the relationship between pregnancy associated plasma protein-A (PAPP-A)and culprit coronary plaque morphology in patients with unstable angina(UA).Methods Sixtyeight UA patients undergoing diagnostic coronary angiography and intravascular ultrasound were included in this study.A sandwich enzyme-linked immunosorbent assay technique was used to assay the circulating PAPP-A.Plaque characteristics of culprit lesion were analyzed for UA patients with various PAPP-A levels.Results PAPP-A level was significantly higher in high-risk UA than in non-high-risk UA[(19.9±20.1)mIU/L vs.(6.9 ±5.7)mIU/L,P=0.002].Optimal threshold of PAPP-A to prediet high-risk UA was determined as 11.0 mIU/L with a sensitivity of 78.6%and a specificity of 77.5%.Patients with higher PAPP-A level(≥11.0 mIU/L)was associated with larger external elastic membrane cross-sectional area,plaque area and more plaque burden compared with patients with lower PAPP-A Ievel(all P<0.01).Positive remodeling,attenuated plaque and plaque rupture were significantly more often in patients with higher PAPP-A than in patients with lower PAPP-A level(all P<0.01).PAPP-A≥11.0 mIU/L(OR=5.921,P=0.014)and attenuated plaque(OR=7.541,P=0.038)were independent risk predictors for high-risk UA.Conclusions PAPP-A was associated with instability of culprit plaque in UA patients.PAPP-A≥11.0 mIU/L and attenuated plaque were independent predictors for high-risk UA.

BACKGROUNDThere are numerous articles on the endothelial progenitor cells (EPCs) in different disease conditions. However, the functional properties of EPCs in acute coronary syndrome (ACS) are still uncertain. Here we aimed to study the number and functions of EPCs in ACS patients.

METHODSPatients were enrolled with admitted ACS (n = 25) and another 25 gender-, age-, atherosclerotic risk factors-matched stable coronary artery disease (CAD) controls. EPCs were defined as CD34(+)/CD133(+)/VEGFR-2(+) and quantified by flow cytometry. Moreover, functional properties of EPCs including colony-forming unit (CFU), proliferation, migration as well as apoptosis were evaluated and compared between the two groups. Plasma matrix metalloproteinase-9 (MMP-9) was detected in all patients as well.

RESULTSThe two groups had similar medication and clinical characteristics on admission. The EPCs in ACS patients were more than 2.6 times that in stable CAD subjects (15.6 ± 2.7 vs. 6.0 ± 0.8/100 000 events, P < 0.01). CFU was not statistically different between the two groups (10.8 ± 2.9 vs. 8.2 ± 1.8, number/well, P > 0.05). Furthermore, EPCs isolated from ACS patients were significantly impaired in their proliferation (0.498 ± 0.035 vs. 0.895 ± 0.067, OD value, P < 0.01) and migration capacity (20.5 ± 3.4 vs. 30.7 ± 4.3, number/well, P < 0.01) compared with controls. Moreover, the apoptosis cell in cultured EPCs was drastically increased in ACS group ((18.3 ± 2.1)% vs. (7.8 ± 0.4)%, P < 0.01).

CONCLUSIONSPatients with ACS exhibited apparently increased circulating EPCs as well as cultured apoptosis percentage together with a remarkable impairment of proliferation and migration activities compared with stable CAD subjects.

Acute Coronary Syndrome ; metabolism ; pathology ; Apoptosis ; physiology ; Cell Movement ; physiology ; Cell Proliferation ; Cells, Cultured ; Endothelial Cells ; cytology ; metabolism ; Female ; Flow Cytometry ; Humans ; Male ; Matrix Metalloproteinase 9 ; metabolism ; Middle Aged ; Stem Cells ; cytology ; metabolism