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 investigate the effect of miR-495-3p targeting budding uninhibited by benzimidazoles(BUB1)on signal transducer and activator of transcription 3(STAT3)signaling pathway on biological behavior of esophageal cancer(EC)cells.Methods The differentially expressed genes in EC tissues and normal tissues were screened by the cDNA microarray technique.The differentially expressed genes were analyzed by bioinformatics methods.The target genes of miRNAs were predicted by the TargetScan database and verified by a dual luciferase gene reporter assay.KYSE150 cells were divided into blank control group,NC mimics group and miR-495-3p mim-ics group.The activity of KYSE150 cells were detected by the CCK-8 method.Cell cycle and apoptosis were meas-ured by flow cytometry.The expression of BUB1 mRNA was measured by real-time fluorescence quantitative reverse transcription polymerase chain reaction(RT-qPCR).The levels of BUB1,STAT3,phosphor(p)-STAT3,cyclin dependent kinase 1(CCNB1),cyclin dependent kinase 1(CDK1),B-cell lymphoma-2(Bcl-2),cysteinyl aspar-tate-specific proteinase-3(Caspase-3)and cysteinyl aspartate-specific proteinase-3(Caspase-9)were measured by Western blot.The migration and invasion abilities of the cells were measured by wound-healing and Transwell inva-sion assays.Results Differentially expressed genes were involved in biological processes,signaling pathways and network construction,which were mainly related to cell cycle.BUB1 is the key(Hub)gene,and BUB1 is the tar-get gene of miR-495-3p.In vitro experiments showed that overexpression of miR-495-3p could significantly inhibit the migration and invasion of EC cells and induce apoptosis and G2/M phase arrest.After treatment with overex-pression of miR-495-3p,the expression of Caspase-3 and Caspase-9 in EC cells increased significantly(P＜0.01),while the expression of Bcl-2,BUB 1,CCNB1,CDK1 and p-STAT3 decreased significantly(P＜0.01).Moreover,the STAT3 signaling pathway might play an important role in this process.Conclusion miR-495-3p may influence the biological behavior of esophageal cancer cells by down-regulating BUB 1-mediated STAT3 signaling pathway.

As a potential vectored vaccine,Newcastle disease virus(NDV)has been subject to various studies for vaccine development,while relatively little research has outlined the immunomodulatory effect of the virus in antigen presentation.To elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells(DCs)and T cells,DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide(LPS)for further detection by enzyme-linked immunosorbent assay(ELISA),flow cytometry,immunoblotting,and quantitative real-time polymerase chain reaction(qRT-PCR).The results revealed that NDV infection resulted in the inhibition of interleukin(IL)-12p40 in DCs through a p38 mitogen-activated protein kinase(MAPK)-dependent manner,thus inhibiting the synthesis of IL-12p70,leading to the reduction in T cell proliferation and the secretion of interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),and IL-6 induced by DCs.Consequently,downregulated cytokines accelerated the infection and viral transmission from DCs to T cells.Furthermore,several other strains of NDV also exhibited inhibitory activity.The current study reveals that NDV can modulate the intensity of the innate?adaptive immune cell crosstalk critically toward viral invasion improvement,highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.

Objective:To investigate the predictive ability of Glypican-3 (GPC3) positive hepatocellular carcinoma based on the hepatobiliary specific contrast agent gadoxetate disodium enhancement of the liver imaging reporting and data system version 2018 (LI-RADS v2018) imaging features, and to assess the relevant clinical imaging features for postoperative recurrence in GPC3 positive HCC patients.Methods:This study was a cohort study. A total of 122 hepatocellular carcinoma patients who underwent gadoxetate disodium enhanced MRI examination with hepatic tumor resection in Henan Provincial People′s Hospital from January 2017 to December 2021 were retrospectively collected, including 96 GPC3 positive and 26 GPC3 negative patients. The imaging features defined by LI-RADS v2018 of HCC lesions were analyzed. Patients were followed up for 40 months to determine recurrence free survival (RFS). The logistic regression was used to analyze the risk factors of GPC3 positivity. An imaging model, and a clinical-imaging model which combined the patient′s alpha-fetoprotein levels were constructed. The efficacy of the model for predicting GPC3 positivity was assessed using receiver operating characteristic curves. Kaplan-Meier method was used to draw the survival curve, and the log-rank test was used to compare the RFS between GPC3 positive and negative patients. Risk factors affecting the recurrence of GPC3 positive HCC were assessed by Cox regression.Results:The results of logistic multivariate regression analysis confirmed that rim enhancement ( OR=5.685, 95% CI 1.229-26.287, P=0.026) and irregular tumor margin at hepatobiliary phase ( OR=4.431, 95% CI 1.684-11.663, P=0.003) were independent risk factors for GPC3 positive HCC. The area under the curve for predicting GPC3 positivity was 0.745 (95% CI 0.636-0.854) for the imaging model and 0.776 (95% CI 0.677-0.876) for the clinical-imaging model. The mean RFS in the GPC3 positive group was 22 months, and it was 32 months in the negative group. There was a statistically significant difference in RFS between the two groups ( χ2=5.15, P=0.023). The multivariate Cox regression analysis showed that the arterial rim enhancement ( HR=5.460, 95% CI 1.966-15.162, P=0.001), microvascular invasion ( HR=2.402, 95% CI 1.210-4.769, P=0.012), portal vein tumor thrombus ( HR=3.226, 95% CI 1.114-9.344, P=0.031) were independent risk factors for recurrence after hepatic tumor resection for GPC3-positive HCC. Conclusions:A model based on the LI-RADS v2018 imaging features of hepatobiliary specific contrast agent gadoxetate disodium enhancement can effectively predict GPC3 positive HCC. The arterial rim enhancement, microvascular invasion and portal vein tumor thrombus are independent risk factors for postoperative recurrence of GPC3 positive HCC.

The clinical practice guidelines of traditional Chinese medicine （TCM） have problems such as limited clinical application and unclear implementation effects， which may be related to the lack of clinical practice evidence. To provide reliable and precise evidence for clinical practice， this article proposes a model of combining TCM guidelines with real-world study， which includes 4 steps. Firstly， during the implementation process of the guidelines， a high-quality research database is established. Secondly， the recommendations in the guidelines are evaluated based on the established database in multiple dimensions， including applicability， effectiveness， safety， and cost-effectiveness， and thus their effectiveness in practical applications can be determined. Thirdly， based on the established database， core prescriptions are identified， and the targeted populations and medication plans are determined. That is， the best treatment regimen is established based on the analysis of abundant clinical data regarding the effects of different medication frequencies， dosages， and duration on efficacy. Fourthly， the guidelines are updated according to the real-world evidence. The research based on this model can provide real-world evidence for ancient and empirical prescriptions， improving their application in clinical practice. Moreover， this model can reduce research costs and improve research efficiency. When applying this model， researchers need to pay attention to the quality of real-world evidence， ensuring that it can truly reflect the situation in clinical practice. In addition， importance should be attached to the clinical application of guideline recommendations， ensuring that doctors can conduct standardized diagnosis and treatment according to the guidelines. Finally， full-process participation of multidisciplinary experts is encouraged to ensure the comprehensiveness and scientificity of the study. In conclusion， the application of this model will contribute to the development of TCM guidelines responsive to the needs of clinical practice and achieve the goal of promoting the homogenization of TCM clinical diagnosis and treatment.

As a supplement to randomized controlled trials， observational studies can provide evidence for the effectiveness of traditional Chinese medicine （TCM） treatment measures. They can also study influencing factors of diseases， etiology， and prognosis. However， there is a confounding effect due to the lack of randomization， which seriously affects the causal inference between the study factors and the outcome， resulting in confounding bias. Therefore， identifying and controlling confounding factors are key issues to be addressed in TCM observational studies. According to the causal network and the characteristics of TCM theory， confounding factors can be categorized into measured and unmeasured confounding factors. In addition， attention must be paid to identifying confounding factors and intermediate variables， as well as the interaction between confounding factors and study factors. For methods of controlling confounding factors， measured confounding factors can be controlled by stratification， multifactor analysis， propensity scores， and disease risk scores. Unmeasured and unknown confounding factors can be corrected using instrumental variable methods， difference-in-difference methods， and correction for underlying event rate ratios. Correcting and controlling confounding factors can ensure a balance between groups， and confounding bias can be reduced. In addition， methods such as sensitivity analysis and determination of interactions make the control of confounding factors more comprehensive. Due to the unique characteristics of TCM， observational studies of TCM face unique challenges in identifying and controlling confounding factors， including the ever-changing TCM treatment measures received by patients， the often-overlooked confounding effects in the four diagnostic information of TCM， and the lack of objective criteria for TCM evidence-based diagnosis. Some scholars have already conducted innovative explorations to address these issues， providing a methodological basis for conducting higher-quality TCM observational studies， so as to obtain more rigorous real-world evidence of TCM and gradually develop quality evaluation criteria for OS that are consistent with the characteristics of TCM.

Standardized reporting is a crucial factor affecting the use of patient guidelines （PGs）， particularly in the reporting and presentation of recommendations. This paper introduced the current status of PG reporting， including the research on PG content and presentation formats， and provided comprehensive recommendations for PG reporting from aspects such as overall framework， recommendations， presentation format， and readability. First， the presentation of PG recommendations should include clearly defined clinical questions， recommendations and their rationale， and guidance on how patients should implement the interventions； for specific content in the PG， such as level of evidence， level of recommendation， it is recommended to explain in text the reasons for giving different levels of recommendation， i.e.， to present the logic behind giving the level of recommendation to the patient； additional information needed in the recommendation framework should be supplemented by tracing references or authoritative textbooks and literature that support the recommendations. Subsequently， the PG text should be written based on the Reporting Checklist for Public Versions of Guidelines （RIGHT-PVG） reporting framework. Finally， to enhance readability and comprehension， it is recommended to refer to the Patient Education Materials Assessment Tool （PEMAT） for translating PG content. To enhance the readability of PGs， it is suggested to present the PG content in a persona-lized and layered manner.

The classification of traditional Chinese medicine （TCM） syndromes is one of the core technical elements in the industry standard of Specification of Diagnosis and Therapeutic Effect Evaluation of Diseases and Syndromes in TCM. In the past，when clinical standards for TCM were formulated，the determination of TCM syndrome classification relied heavily on textbooks and expert experience，lacking systematic research. This approach thus failed to reflect the advancement and scientificity of the standards，thereby affecting their implementation and application. This article reviewed the presentation forms and technical methods of TCM syndrome classification，including the two-tier syndrome classification model with primary and secondary symptoms，as well as the application of modern literature research，ancient literature research，Delphi method，in-depth expert interviews，consensus conferences，and real-world research. When syndrome classification standards are developed，it is necessary to build upon modern literature research，adopt a mixed approach combining qualitative research and quantitative analysis results，and reach expert consensus through consensus conferences. Through systematic research，the scientificity，applicability，and coordination of TCM syndrome classification standards can be enhanced，providing guidance for the standardization of TCM.

Since the concept of patient versions of guidelines （PVGs） was introduced into China， several PVGs have been published in China， but we found that there is a big difference between the concept of PVG at home and abroad， and the reason for this difference has not been reasonably explained， which has led to ambiguity and even misapplication of the PVG concept by guideline developers. By analyzing the background and purpose of PVGs， and the understanding of the PVG concept by domestic scholars， we proposed the term patient guidelines （PGs）. This refers to guidelines developed under the principles of evidence-based medicine， centered on health issues that concern patients， and based on the best available evidence， intended for patient use. Except for the general attribute of providing information or education， which is typical of common health education materials， PGs also provide recommendations and assist in decision-making， so PGs include both the patient versions of guidelines （PVG） as defined by the Guidelines International Network （GIN） and "patient-directed guidelines"， i.e. clinical practice guidelines resulting from the adaptation or reformulation of recommendations through clinical practice guidelines.

At present， the process and methodology of patient guidelines （PGs） development varies greatly and lacks systematic and standardised guidance. In addition to the interviews with PG developers， we have sorted out the relevant methodology for the adaptation and development of existing clinical practice guideline recommendations and facilitated expert deliberations to achieve a consensus， so as to finally put forward a proposal for guidance on the process and methodology for the development of PGs. The development of PGs can be divided into the preparation stage， the construction stage， and the completion stage in general， but the specific steps vary according to the different modes of development of PGs. The development process of Model 1 is basically the same as the patient version of the guideline development process provided by the International Guidelines Network， i.e.， team formation， screening of recommendations， guideline drafing， user testing and feedback， approval and dissemination. The developer should also first determine the need for and scope of translating the clinical practice guideline into a patient version during the preparation phase. Model 2 adds user experience and feedback to the conventional clinical practice guideline development process （forming a team， determining the scope of the PG， searching， evaluating and integrating evidence， forming recommendations， writing the guideline， and expert review）. Based on the different models， we sort out the process and methods of PG development and introduce the specific methods of PG development， including how to identify the clinical problem and how to form recommendations based on the existing clinical practice guidelines， with a view to providing reference for guideline developers and related researchers.