The Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines （hereinafter referred to as the Guidelines） is first specialized in the field of drug safety for oral Chinese patent medicines （OCPMs） in China. Rooted in China's healthcare context， the Guidelines address the unique usage patterns and risk characteristics of OCPMs， filling a regulatory gap in the pharmacovigilance framework specific to this category. To facilitate accurate understanding and effective implementation of the Guidelines， and to promote the standardized development of pharmacovigilance practices for OCPMs， this study offered a systematic interpretation based on its three core components. In the domain of risk monitoring and reporting， the paper analyzed the rationale for multi-source information integration and clarified the criteria for identifying key products and target populations for intensive monitoring. Regarding risk assessment， the Guidelines were examined from three dimensions of formulation components， medication behaviors， and population to address complex safety issues arising from medicinal constituents， irrational use， and individual susceptibility. In the area of risk control， the analysis focused on context-based interventions and dynamic closed-loop management strategies， exploring practical pathways to shift from passive response to proactive risk mitigation. Furthermore， this paper evaluated the applied value of the Guidelines and identified implementation challenges， such as insufficient capacity at the primary-care level and limited digital infrastructure. In response， the study proposed optimization strategies including establishing a dynamic updating mechanism， strengthening training at the grassroots level， and incorporating artificial intelligence to enhance pharmacovigilance capacity. This interpretation aims to provide actionable insights for marketing authorization holders （including manufacturers）， pharmaceutical distributors， healthcare institutions， and research organizations， ultimately supporting the establishment and refinement of a full lifecycle pharmacovigilance system for OCPMs.

ObjectiveThis paper aims to investigate the traditional Chinese medicine syndrome types in patients with chronic hepatitis B （CHB） complicated by metabolic dysfunction-associated fatty liver disease （MAFLD） and explore the correlations between these syndrome types and clinical indicators， as well as ocular manifestation characteristics， thereby providing a reference for syndrome differentiation and treatment strategies in traditional Chinese medicine. MethodsGeneral data， information from the four diagnostic methods of traditional Chinese medicine， clinical indicators， and ocular manifestation data were collected from 506 patients with CHB complicated by MAFLD enrolled at the Public Health Clinical Center of Chengdu between June 2024 and December 2024. Cluster analysis， principal component analysis， and complex network models were employed to identify the distribution patterns of traditional Chinese medicine syndromes. Correlations between different syndrome types and clinical indicators， as well as ocular manifestation characteristics， were further analyzed. ResultsThe predominant syndromes identified in patients with CHB complicated by MAFLD were dampness and heat accumulation （51.58%）， liver depression with spleen deficiency （31.62%）， blood stasis obstructing collaterals （8.89%）， and Qi-Yin deficiency （7.91%）. No statistically significant differences were found among the four syndrome types in routine blood tests and liver function indicators. However， patients with the dampness and heat accumulation type exhibited significantly higher levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， liver stiffness measurement （LSM）， controlled attenuation parameter （CAP）， and alpha-fetoprotein （AFP）， along with lower levels of high-density lipoprotein cholesterol （HDL-C）， compared with those with other syndrome types. Regarding ocular manifestations， the incidence of moon halo signs was significantly higher in patients with the blood stasis obstructing collaterals type than in those with other syndrome types. Additionally， the incidence in scleral zone 3 （corresponding to the large intestine） was higher in patients with the damp and heat accumulation type. ConclusionDampness and heat accumulation is the core syndrome type in patients with CHB complicated by MAFLD， commonly accompanied by spleen deficiency， liver depression， blood stasis， and Yin deficiency. A complex syndrome pattern characterized by a predominance of dampness and heat， along with a mixture of deficiency and excess， is formed. Different traditional Chinese medicine syndrome types are associated with distinct clinical indicators and ocular manifestation characteristics. Among them， patients with the dampness and heat accumulation type exhibit more pronounced metabolic disturbances and liver injury， whereas those with the blood stasis type show a higher incidence of moon halo signs. Abnormalities in scleral zone 3 are also more prevalent in patients with dampness and heat type.

Objective:To investigate the value of coronary CTA (CCTA)-based traditional features and radiomics of plaque in the identification of culprit lesions that caused acute myocardial infarction (AMI).Methods:This was a retrospective multicenter study. From July 2016 to November 2023, a total of 344 patients from the Affiliated Hospital of Qingdao University (training cohort, n=184), Shandong Provincial Hospital Affiliated to Shandong First Medical University (validation cohort, n=88) and Qilu Hospital of Shandong University (test cohort, n=72) who received percutaneous coronary intervention (PCI) due to AMI and underwent CCTA within 48 hours of AMI were enrolled. The culprit plaques and non-culprit plaques were identified using a combination of electrocardiogram, CCTA, and angiographic findings. The vessel, plaque location, plaque type, Coronary Artery Disease-Reporting and Data System (CAD-RADS) score, high-risk plaque characteristics, plaque length, plaque volume, and burden were analyzed, and 1 904 radiomics features were extracted for each plaque. The traditional imaging model, the radiomics model, and the combined model were established by using multivariate Logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of each model in identifying culprit lesions. The DeLong test was used for the comparison of AUC between every two models. The net reclassification index (NRI) was used to evaluate the incremental value of the combined model to the traditional imaging model and the radiomics model. The decision curve analysis (DCA) was used to assess the clinical net benefit of these models. A correlation heatmap was used to evaluate the correlation between the radiomics score and traditional CCTA factors. The interpretable analysis of the decision process of the combined model was performed by the Shapley Additive exPlanations (SHAP). Results:In the validation cohort and the test cohort, the AUC of the traditional imaging model developed by the vessel, plaque type, positive remodeling and CAD-RADS score was 0.898 (95% CI 0.869-0.922) and 0.881 (95% CI 0.848-0.910), respectively. The radiomics model developed by six radiomics features was 0.863 (95% CI 0.831-0.891) and 0.863 (95% CI 0.827-0.864), respectively. The AUC of the combined model was 0.930 (95% CI 0.905-0.950)and 0.919 (95% CI 0.889-0.942), respectively. In the validation cohort and the test cohort, the AUC of the combined model was higher than that of the traditional imaging model ( Z=4.013, 4.272, P<0.001) and that of the radiomics model ( Z=4.819, 3.784, P<0.001), respectively. In the validation cohort, the combined model yielded an NRI of 20.43% (95% CI 10.43%-30.44%, P<0.001) and 20.21% (95% CI 9.62%-30.80%, P<0.001) for identifying culprit lesions compared with the traditional imaging model and the radiomics model, respectively. In the test cohort, the combined model yielded an NRI of 28.05% (95% CI 16.72%-39.38%, P<0.001) and 23.57% (95% CI 13.58%-33.56%, P<0.001) for identifying culprit lesions compared with the traditional imaging model and the radiomics model, respectively. DCA showed the combined model had the highest clinical net benefit. The correlation heatmap showed the radiomics score was not correlated or only weakly correlated with traditional CCTA factors. SHAP indicated the radiomics and CAD-RADS score contributed significantly to the model. Conclusion:The CCTA-based traditional features and radiomics of plaque have favorable performance for the identification of culprit plaques in patients with AMI.

Objective To identify determinants affecting the implementation of outpatient mutual aid policy and propose evidence-based optimization strategies.Methods By utilizing the Horn-Mitton policy implementation framework,this article sys-tematically examined implementation barriers through multi-dimensional analysis.Results The implementation process was con-strained by multiple interacting factors:overly broad policy objectives,insufficient adoption of digital health technologies,shorta-ges of health insurance professionals,policy fragmentation due to lack of horizontal communication within organizations,an in-complete fiscal compensation mechanism,imbalance of cohesive policies,and limited public acceptance.These factors collective-ly hindered the advancement of outpatient mutual aid policy.Conclusion In order to improve the implementation efficacy,it is urgent to build robust digital monitoring platforms equipped with regulatory systems,establish multi-dimensional fiscal compensa-tion mechanisms,cooperate with a variety of policies to promote coordination,explore reform plans for employee health insurance payment fairness,unify the reimbursement level orientations,and construct differentiated reimbursement policy systems.

Objective To identify determinants affecting the implementation of outpatient mutual aid policy and propose evidence-based optimization strategies.Methods By utilizing the Horn-Mitton policy implementation framework,this article sys-tematically examined implementation barriers through multi-dimensional analysis.Results The implementation process was con-strained by multiple interacting factors:overly broad policy objectives,insufficient adoption of digital health technologies,shorta-ges of health insurance professionals,policy fragmentation due to lack of horizontal communication within organizations,an in-complete fiscal compensation mechanism,imbalance of cohesive policies,and limited public acceptance.These factors collective-ly hindered the advancement of outpatient mutual aid policy.Conclusion In order to improve the implementation efficacy,it is urgent to build robust digital monitoring platforms equipped with regulatory systems,establish multi-dimensional fiscal compensa-tion mechanisms,cooperate with a variety of policies to promote coordination,explore reform plans for employee health insurance payment fairness,unify the reimbursement level orientations,and construct differentiated reimbursement policy systems.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective To observe the clinical characteristics and efficacy of plasma exchange artificial liver therapy in patients with acute-on-chronic liver failure(ACLF).Methods A total of 135 patients with ACLF treated in our hospital from May 2023 to May 2024 were selected as the study subjects.They were divided into two groups based on different treatment methods:plasma exchange artificial liver therapy group(54 cases)and conventional therapy group(81 cases).Patients received different treatment according their liver function and coagulation function.We compared the laboratory test results,clinical efficacy,cytokine levels,and incidence of complications between the two groups of patients.Results The MELD score of patients was significantly higher in the artificial liver treatment group(2 527.96±1 504.21)than in the conventional group(1 854.75±940.23)(P=0.004),and the incidence of diabetes,coronary heart disease and liver cancer in the former group was significantly higher than that in the latter group(P=0.030,0.030).The total serum bilirubin,direct bilirubin,interleukin-6(IL-6),C-reactive protein(CRP),alpha fetoprotein,lymphocyte/monocyte ratio,and direct bilirubin/partial thromboplastin time ratio(PTR)in the artificial liver treatment group were significantly higher than those in the conventional group(P values＜0.001,＜0.001,0.040,0.030,0.040,and 0.006,respetively),while uric acid levels were significantly lower than those in the conventional group(P=0.040).The artificial liver treatment group had significantly lower incidence of infection and ascites during treatment than the conventional group(P=0.010,0.020).After artificial liver treatment,the patients' levels of IL-6,CRP,and alpha fetoprotein were significantly reduced.Conclusion Patients with complex chronic and acute liver failure are more recommended to directly undergo plasma exchange artificial liver treatment,which has definite efficacy and fewer complications.IL-6,CRP and alpha fetoprotein dynamically monitored can be regarded as indicators for efficacy of artificial liver treatment.

Objective To evaluate the efficacy and safety of using stent semi-retrieval technique during mechanical thrombectomy(MT)for acute anterior cerebral artery(ACA)occlusion.Methods We made a retrospective analysis of 38 patients with acute ACA occlusion treated by stent semi-retrieval technique at Tangdu Hospital and Xi'an No.1 Hospital from June 2019 to September 2023.The successful recanalization,first-pass effect(FPE),perioperative complications and postoperative recovery of all the patients were analyzed.Modified thrombolytic test in cerebral infarction(mTICI)was used to evaluate the recanalization(unsuccessful recanalization,mTICI 0-2a;successful recanalization,mTICI 2b-3).FPE was defined as mTICI 3 after one thrombectomy.The clinical outcome was evaluated by modified Rankin Scale(mRS)3 months postoperatively.A good prognosis was defined as a mRS 0-2.Results Of the 38 patients,36(94.7％)got successful recanalization(mTICI 2b-3),with an FPE of 73.7％(28/38).Two cases of mild vascular spasm(5.3％)occurred during the mechanical thrombectomy,which completely relieved without further treatment.None of the 38 patients experienced vascular rupture or dissection,and no thrombus escaped during the thrombus removal process.There was no subarachnoid hemorrhage or parenchymal hemorrhage in the area related to ACA occlusion.Ninety days after operation,14 cases(36.8％)reached good outcome(mRS 0-2),18 cases(47.4％)reached mRS 3-5,and 6 cases(15.8％)died.Conclusion Our preliminary experience suggests that the stent semi-retrieval technique may be a safe and effective method for treating acute anterior cerebral artery occlusion.

Objective To investigate the effect of mutation human proprotein convertase subtilism/kexin type 9(hPCSK9D374Y)in PCSK9 gene on methionine choline deficiency diet(MCD)-induced nonalcoholic steato-hepatitis(NASH)in mice.Methods Sixteen C57BL/6J wild-type mice were selected and randomly divided into the hPCSK9D374Y group and the control GFP group.MCD was fed for 6 weeks,and then the serum level of hepatic triglyceride,alanine aminotransferase(ALT)and aspartate aminotransferase(AST)was examined.Oil Red O and Sirius Red staining microscopy were used to identify hepatic lipid infiltration and fibrosis severity.F4/80-positive cell infiltration was analyzed using immunohistochemistry.Lipid synthesis and inflammatory response-related proteins were detected by Western blot and related mRNA expression was analyzed by RT-qPCR.Results Hepatic hPCSK9 protein and mRNA were significantly up-regulated,LDLR protein expression was down-regulated,and ser-um level of ALT and AST was significantly elevated in the hPCSK9D374Y group of mice(P＜0.05).The degree of he-patic steatosis and fibrosis increased and F4/80-positive cells were significantly increased(P＜0.01).FASN and SCD1 proteins were significantly up-regulated and PPARα was down-regulated in the hPCSK9D374Y group;The ex-pression of TLR4 and p-P65 was elevated,whereas the expression of Iκ Bα was decreased(P＜0.001).RT-qPCR re-sults showed a significant increase of mRNA coding inflammatory factors TNF-α,IL-1β,IL-6,and MCP-1,and a significant up-regulation of fibrosis-associated mRNAs(collagen Ⅰα and collagen Ⅲα)was found(P＜0.001).Conclusions Functionally acquired mutation in the PCSK9 gene(hPCSK9D374Y)exacerbates MCD-induced hepatic steatosis,inflammatory response and fibrosis in mice.

AIM To study the chemical constituents from Stelmatocrypton khasianum.(Benth.)Baill.and their in vitro anti-inflammatory activity and cytotoxic activity.METHODS Separation and purification were performed using thin layer chromatography,silica gel,semi-preparative HPLC and Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The in vitro anti-inflammatory activity was evaluated by RAW264.7 model,and the cytotoxic activity was determined by CCK-8 method.RESULTS Fifteen compounds were isolated and identified as 2α,3β,19α,23-tetrahydroxy-urs-12-en-28-oic acid-3-O-β-D-glucopyranosyl-28-O-β-D-glucopyranosyl ester(1),dalzienoside(2),benzyl-(6-O-α-L-rhanmopyranosyl)O-β-D-glucopyranoside(3),corchorusoside C(4),cyclo(Ala-Tyr)(5),thymidine(6),(4S,5S)-5-hydroxy-4-hexanolide(7),2-methylpyridin-3-ol(8),butyl isobutyl phthalate(9),bis-(2-ethylhexyl)terephthalate(10),p-hydroxybenzaldehyde(11),vanilic acid(12),salicylic acid(13),isovanilic acid(14),3-hydroxy-p-anisaldehyde(15).The IC50 values of compounds 1,2 and 4 for NO were(27.69±5.51),(25.82±3.58)and(23.35±7.09)μmol/L,respectively.The IC50 value of compound 1 on MCF-7 cells was(18.15±6.45)μmol/L.The IC50 values of compound 4 on MCF-7 and HCCC-9810 cells were(19.43±2.66)and(21.76±5.81)μmol/L,respectively.CONCLUSION Compounds 2-11 are isolated from S.khasianum for the first time.Compounds 1,2 and 4 exhibit good in vitro anti-inflammatory activity,and 1,4 have cytotoxic activity.