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 improve the quality evaluation method of Platycodonis Radix, to study the differences in the quality of three-years-old Platycodonis Radix under different harvesting periods, and to determine the optimal harvesting period of Platycodonis Radix. METHODS The leachate, ash, moisture, refractive index and the content of six saponins were used as the quality evaluation indexes. The differences between the herbs of Platycodonis Radix at different harvesting periods were characterized with the help of mathematical and statistical methods. And link the entropy weight method, gray correlation analysis and TOPSIS method were combined to obtain the statistical analysis of the relevant indexes and the quality ranking information of the herbs in different harvesting periods. RESULTS There were significant differences between the quality evaluation indexes of three-years-old Platycodonis Radix at different harvesting periods. The added multi-indicator testing had improved the quality evaluation system of Platycodonis Radix and enhanced the "Drug properties-Effectiveness" linkage of the herbs. And the results of the comprehensive quality evaluation model showed that the herbs harvested around October 21 (Frost’s Descent) were ranked best in terms of comprehensive index. CONCLUSION In order to ensure the quality of Platycodonis Radix, the best harvesting period for three-years-old Platycodonis Radix is determined around the "Frost’s Descent" season, taking into account the characteristics of the herbs' appearance and the material basis of herbs.

Objective To construct a risk prediction score model for serious adverse event (SAE) after cardiac catheterization in patients with adult congenital heart disease (ACHD) and pulmonary hypertension (PH) and verify its predictive effect. Methods The patients with PH who underwent cardiac catheterization in Wuhan Asian Heart Hospital Affiliated to Wuhan University of Science and Technology from January 2018 to January 2022 were retrospectively collected. The patients were randomly divided into a model group and a validation group according to the order of admission. The model group was divided into a SAE group and a non-SAE group according to whether SAE occurred after the catheterization. The data of the two groups were compared, and the risk prediction score model was established according to the results of multivariate logistic regression analysis. The discrimination and calibration of the model were evaluated using the area under the receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow test, respectively. Results A total of 758 patients were enrolled, including 240 (31.7%) males and 518 (68.3%) females, with a mean age of 43.1 (18.0-81.0) years. There were 530 patients in the model group (47 patients in the SAE group and 483 patients in the non-SAE group) and 228 patients in the validation group. Univariate analysis showed statistical differences in age, smoking history, valvular disease history, heart failure history, N-terminal pro-B-type natriuretic peptide, and other factors between the SAE and non-SAE groups (P<0.05). Multivariate analysis showed that age≥50 years, history of heart failure, moderate to severe congenital heart disease, moderate to severe PH, cardiac catheterization and treatment, surgical general anesthesia, and N-terminal pro-B-type natriuretic peptide≥126.65 pg/mL were risk factors for SAE after cardiac catheterization for ACHD-PH patients (P<0.05). The risk prediction score model had a total score of 0-139 points and patients who had a score>50 points were high-risk patients. Model validation results showed an area under the ROC curve of 0.937 (95%CI 0.897-0.976). Hosmer-Lemeshow goodness-of-fit test: χ2=3.847, P=0.797. Conclusion Age≥50 years, history of heart failure, moderate to severe congenital heart disease, moderate to severe PH, cardiac catheterization and treatment, general anesthesia for surgery, and N-terminal pro-B-type natriuretic peptide≥126.65 pg/mL were risk factors for SAE after cardiac catheterization for ACHD-PH patients. The risk prediction model based on these factors has a high predictive value and can be applied to the risk assessment of SAE after interventional therapy in ACHD-PH patients to help clinicians perform early intervention.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons. ALS patients develop progressive muscle atrophy, muscle weak and paralysis, finally died of respiratory failure. ALS is characterized by fast aggression and high mortality. What' s more, the disease is highly heterogeneous with unclear pathogenesis and lacks effective drugs for therapy. In this review, we summarize the main pathological mechanisms and the current drugs under development for ALS, which may provide a reference for the drug discovery in the future.

Objective To analyze the incidence of venous thromboembolism(VTE)in pulmonary patients and explore the assessment and prevention of the risk of pneumonia accompanied VTE.Methods The patients with pneumonia were divided into control group(simple pneumonia)and treatment group(with VTE)according to the condition of VTE.Demographic data,blood routine,coagulation index,liver and kidney function index and blood gas index were collected.Statistical methods like chi square test,t-test and nonparametric rank sum test were applied to compare the differences between the two groups.Finally,the nomogram was established according to the logistic regression results and the receiver operating characteristic(ROC)curve was calculated.Results 106 cases in control group and 29 cases in treatment group.Univariate analysis showed that age,D-dimer,fibrinogen degradation products,white blood cell count,neutrophil count,albumin-globulin ratio were statistically significant(P＜0.05).Multivariate logistic regression analysis suggests that age[odds ratio(OR)=1.052],D-dimer(OR=2.339),and albumin/globulin(OR=0.042)are independent affecting factors for VTE in pneumonia patients.A nomogram was developed and ROC was calculated,the area under curve(AUC)was 0.754.Conclusion High age,elevated D-dimer and decreased albumin/globulin are independent risk factors for VTE in pneumonia patients.More over,the established prediction model has good accuracy.

Objective To investigate the therapeutic effect and mechanism of Yiqi Tongqiao Prescription on nasopharyngeal carcinoma in nude mice.Methods Thirty-two nude mice were randomly divided into normal group,model group,Yiqi Tongqiao Prescription low-and high-dose groups,with eight mice in each group.Except for the normal group,the other groups of nude mice were used to construct a nasopharyngeal carcinoma model.After treatment,the tumor volume of nude mice was measured,the levels of serum transforming growth factor β1(TGF-β1)and vascular endothelial growth factor(VEGF)were detected by enzyme-linked immunosorbent assay(ELISA),the pathological morphology of nasal mucosa was observed by hematoxylin-eosin(HE)staining,the mRNA expressions of tissue inhibitor of metalloproteinase 1(TIMP-1)and matrix metalloproteinase 9(MMP-9)in nasal mucosa were detected by quantitative polymerase chain reaction(PCR),the protein expressions of Wnt-1 andβ-catenin in nasal mucosa were detected by Western Blot.Results Compared with the normal group,the tumor volume of nude mice in the model group was increased,the levels of serum TGF-β1 and VEGF were increased,the mRNA expression level of TIMP-1 in nasal mucosa was decreased,the mRNA expression level of MMP-9 was increased,and the protein expression levels of Wnt-1 and β-catenin in nasal mucosa were increased(all P＜0.05).HE staining results showed structural defects of nasal mucosa,and a large number of eosinophils and other inflammatory cell infiltration.Compared with the model group,the tumor volume of nude mice in the low-and high-dose groups of Yiqi Tongqiao Prescription was reduced,the levels of serum TGF-β1 and VEGF were decreased,the mRNA expression level of TIMP-1 in nasal mucosa was increased,the mRNA expression level of MMP-9 was decreased,and the protein expression levels of Wnt-1 and β-catenin in nasal mucosa were decreased(all P＜0.05)in a dose-dependent manner.HE staining results showed that the morphology of nasal mucosa cells was significantly improved.Conclusion Yiqi Tongqiao Prescription inhibits the activity of MMP-9 through the endogenous regulation of TIMP-1 to maintain the homeostasis of extracellular matrix in nasopharyngeal carcinoma,and inhibits the abnormal activation of Wnt/β-catenin signaling pathway and reduces the release of TGF-β1 and VEGF to reduce tumor angiogenesis,thereby playing a role in tumor inhibition for nude mice with nasopharyngeal carcinoma.

Purpose::Ischemia and hypoxia are the main factors limiting limb replantation and transplantation. Static cold storage (SCS), a common preservation method for tissues and organs, can only prolong limb ischemia time to 4 - 6 h. The normothermic machine perfusion (NMP) is a promising method for the preservation of tissues and organs, which can extend the preservation time in vitro by providing continuous oxygen and nutrients. This study aimed to evaluate the difference in the efficacy of the 2 limb preservation methods. Methods::The 6 forelimbs from beagle dogs were divided into 2 groups. In the SCS group ( n = 3), the limbs were preserved in a sterile refrigerator at 4 °C for 24 h, and in the NMP group ( n = 3), the perfusate prepared with autologous blood was used for the oxygenated machine perfusion at physiological temperature for 24 h, and the solution was changed every 6 h. The effects of limb storage were evaluated by weight gain, perfusate biochemical analysis, enzyme-linked immunosorbent assay, and histological analysis. All statistical analyses and graphs were performed using GraphPad Prism 9.0 one-way or two-way analysis of variance. The p value of less than 0.05 was considered to indicate statistical significance. Results::In the NMP group, the weight gained percentage was 11.72% ± 4.06%; the hypoxia-inducible factor-1α contents showed no significant changes; the shape of muscle fibers was normal; the gap between muscle fibers slightly increased, showing the intercellular distance of (30.19 ± 2.83) μm; and the vascular α-smooth muscle actin (α-SMA) contents were lower than those in the normal blood vessels. The creatine kinase level in the perfusate of the NMP group increased from the beginning of perfusion, decreased after each perfusate change, and remained stable at the end of perfusion showing a peak level of 4097.6 U/L. The lactate dehydrogenase level of the NMP group increased near the end of perfusion and reached the peak level of 374.4 U/L. In the SCS group, the percentage of weight gain was 0.18% ± 0.10%, and the contents of hypoxia-inducible factor-1α increased gradually and reached the maximum level of (164.85 ± 20.75) pg/mL at the end of the experiment. The muscle fibers lost their normal shape and the gap between muscle fibers increased, showing an intercellular distance of (41.66 ± 5.38) μm. The contents of vascular α-SMA were much lower in the SCS group as compared to normal blood vessels.Conclusions::NMP caused lesser muscle damage and contained more vascular α-SMA as compared to SCS. This study demonstrated that NMP of the amputated limb with perfusate solution based on autologous blood could maintain the physiological activities of the limb for at least 24 h.

Objective:To investigate the changes of artemin protein expression in diabetic peripheral neuropathy (DPN) and to explore the regulatory effect of human adipose-derived stem cell (ADSC) exosomes on the change of artemin protein expression.Methods:This research was a prospective observational clinical research combined with experimental research. Thirteen DPN patients (9 males and 4 females, aged 32 to 68 years) who were admitted to the First Affiliated Hospital of Air Force Medical University (hereinafter referred to as our hospital) from May 2022 to October 2023 and met the inclusion criteria were selected as DPN group, and 5 non-diabetes patients (4 males and 1 female, aged 29 to 61 years) who were admitted to our hospital in the same period of time and met the inclusion criteria were selected as control group. The toe nerve or sural nerve tissue in the abandoned tissue after debridement or amputation of patients in the two groups was collected. The pathological changes of nerve tissue were observed after hematoxylin-eosin staining; the protein expressions of S100β and artemin in nerve tissue were observed after immunofluorescence staining, and the artemin protein expression was quantified; the protein and mRNA expressions of artemin were detected by Western blotting and real-time fluorescent quantitative reverse transcription polymerase chain reaction, respectively (the sample number in DPN group and control group was 13 and 5, respectively). Twelve male C57BL/6 mice aged 3 to 5 days were collected to isolate Schwann cells, and the cells were divided into conventional culture group cultured routinely, high glucose alone group (cultured with high concentration of glucose solution only), and high glucose+exosome group (cultured with high concentration of glucose solution and extracted human ADSC exosomes). After 24 hours of culture, the cell proliferation activity was detected by cell counting kit 8 ( n=6). After 48 hours of culture, the protein expression of artemin was detected by Western blotting ( n=3). Results:Compared with those in control group, the neural supporting cells decreased and the inflammatory cells increased in the nerve tissue of patients in DPN group, showing typical manifestations of nerve injury. Immunofluorescence staining showed that compared with those in control group, the nuclei was more, and the protein expression of S100β was lower in nerve tissue of patients in DPN group. The protein expression of artemin in nerve tissue of patients in DPN group was 71±31, which was significantly lower than 1 729±62 in control group ( t=76.92, P<0.05). Western blotting detection showed that the protein expression of artemin in nerve tissue of patients in DPN group was 0.74±0.08, which was significantly lower than 0.97±0.06 in control group ( t=5.49, P<0.05). The artemin mRNA expression in nerve tissue of patients in DPN group was significantly lower than that in control group ( t=7.65, P<0.05). After 24 hours of culture, compared with that in conventional culture group, the proliferation activities of Schwann cells in high glucose alone group and high glucose+exosome group were significantly decreased ( P<0.05); compared with that in high glucose alone group, the proliferation activity of Schwann cells in high glucose+exosome group was significantly increased ( P<0.05). After 48 hours of culture, compared with those in conventional culture group, the protein expressions of artemin of Schwann cells in high glucose alone group and high glucose+exosome group were significantly decreased ( P<0.05); compared with that in high glucose alone group, the protein expression of artemin of Schwann cells in high glucose+exosome group was significantly increased ( P<0.05). Conclusions:The protein expression of artemin in nerve tissue of DPN patients is lower than that in normal nerve tissue, which may be related to the reduction of proliferation activity of Schwann cells by high glucose. Human ADSC exosomes may improve the proliferation activity of Schwann cells by increasing artemin protein expression, thereby delaying the progression of DPN.

Objective To carry out accurate quantative evaluation of MRI scanning noise based on laser vibrometry technology.Methods Skull and spine MRI was performed with mute and conventional sequences.A laser vibrometry device was used to sample the surface vibration noise at the outer edge of the inspection hole of MRI system according to GB/T 16539-1996 Acoustics—Determination of sound power levels of noise sources using vibration velocity—Measurement for seal machinery,and the indicators of sound power level,sound pressure level and perceived noise level obtained by the three calculation methods(LPN1,LPN2 and LPN3)were analyzed with some dedicated MRI noise analysis software.Results The peak sound pressure levels for conventional and mute sequences of skull scanning were 81 and 63 dB(A),respectively,and mute sequence reduced the noise level significantly;the peak sound pressure levels for conventional and mute sequences of spine scanning were 79 and 75 dB(A),respectively,and the noise reduction level was significantly lower than that of skull scanning.Significant differences in noise reduction were not found in spine scanning sequences,while were found in skull scanning sequences.During spine and skull scanning LPN1,LPN2 and LPN3 obtained by the three calculation methods of conventional and mute sequences were all higher than the overall sound power and overall pressure levels obviously.Conclusion Mute sequence can not realize linear noise reduction for the whole frequency band,the perceived noise of the human ear during MRI scanning is related directly to the scanning sequence,and there may be some bias when only one physical indicator is involved in the noise evaluation of MRI system.[Chinese Medical Equipment Journal,2024,45(10):20-24]

Non-communicable diseases(NCDs),including cardiovascular diseases,cancer,metabolic diseases,and skeletal diseases,pose significant challenges to public health worldwide.The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage.Nuclear factor erythroid 2-related factor 2(Nrf2),a critical transcription factor,plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury.Therefore,Nrf2-targeting therapies hold promise for preventing and treating NCDs.Quercetin(Que)is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties.It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation.Que modulates mitochondrial function,apoptosis,autophagy,and cell damage biomarkers to regulate oxidative stress and inflammation,highlighting its efficacy as a therapeutic agent against NCDs.Here,we discussed,for the first time,the close association between NCD pathogenesis and the Nrf2 signaling pathway,involved in neurodegenerative diseases(NDDs),cardiovascular disease,cancers,organ damage,and bone damage.Furthermore,we reviewed the availability,pharmacokinetics,pharmaceutics,and therapeutic applica-tions of Que in treating NCDs.In addition,we focused on the challenges and prospects for its clinical use.Que represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.