To develop the Pharmacovigilance Guidelines for Clinical Application of Chinese Patent Medicines for Mucosal Administration in response to common problems， including insufficient safety information in package inserts， amplified medication risks in special populations， and non-standard clinical practices， thus establishing a risk management system tailored to the characteristics of Chinese patent medicines for mucosal administration. An approach combining qualitative and quantitative methods was adopted. In accordance with the Drug Administration Law of the People's Republic of China （2019 revision） and the GB/T 1.1—2020 standard， a systematic search was performed in the Chinese Pharmacopoeia （2020 edition）， the Catalog of Medicines Covered by Medical Insurance （2022 edition）， Chinese databases ［China Network of Knowledge Infrastructure （CNKI）， Wanfang Data （Wanfang）， and VIP journal resource integration service platform （VIP）］， and international databases （Cochrane Library， PubMed， and EMbase）. Guideline outlines were developed through questionnaire surveys， expert interviews， and the nominal group technique. The content of each item was formulated with full consideration of traditional Chinese medicine （TCM） incompatibility， as well as the conceptual connotations and extensions of pharmacovigilance. The results included 54 Chinese patent medicines for mucosal administration from the Chinese Pharmacopoeia （2020 edition） and 58 from the Catalog of Medicines Covered by Medical Insurance （2022 edition）. Safety-related items in the corresponding package inserts were collected， and 27 relevant publications were retrieved. Thirty experts from 24 institutions were mobilized for the drafting， and opinions from 61 external experts were solicited. A pharmacovigilance framework was established， covering the full chain of "monitoring， identification， assessment， and control". Based on seven anatomical sites， including nasal， ocular， and oral mucosa， a stratified monitoring system was constructed. The guideline proposed key recommendations on improving package insert sections such as "Adverse Reactions"， "Contraindications"， and "Precautions"， clinical procedure standardization in healthcare institutions， risk control， and dynamic pharmacovigilance. The Guideline provides evidence-based support tailored to the risk profile of Chinese patent medicines for mucosal administration， filling the current gap in international pharmacovigilance standards in this field， while offering technical support for safety management across the full life cycle of medicines for mucosal administration.

To develop the Pharmacovigilance Guidelines for Clinical Application of Chinese Patent Medicines for Mucosal Administration in response to common problems， including insufficient safety information in package inserts， amplified medication risks in special populations， and non-standard clinical practices， thus establishing a risk management system tailored to the characteristics of Chinese patent medicines for mucosal administration. An approach combining qualitative and quantitative methods was adopted. In accordance with the Drug Administration Law of the People's Republic of China （2019 revision） and the GB/T 1.1—2020 standard， a systematic search was performed in the Chinese Pharmacopoeia （2020 edition）， the Catalog of Medicines Covered by Medical Insurance （2022 edition）， Chinese databases ［China Network of Knowledge Infrastructure （CNKI）， Wanfang Data （Wanfang）， and VIP journal resource integration service platform （VIP）］， and international databases （Cochrane Library， PubMed， and EMbase）. Guideline outlines were developed through questionnaire surveys， expert interviews， and the nominal group technique. The content of each item was formulated with full consideration of traditional Chinese medicine （TCM） incompatibility， as well as the conceptual connotations and extensions of pharmacovigilance. The results included 54 Chinese patent medicines for mucosal administration from the Chinese Pharmacopoeia （2020 edition） and 58 from the Catalog of Medicines Covered by Medical Insurance （2022 edition）. Safety-related items in the corresponding package inserts were collected， and 27 relevant publications were retrieved. Thirty experts from 24 institutions were mobilized for the drafting， and opinions from 61 external experts were solicited. A pharmacovigilance framework was established， covering the full chain of "monitoring， identification， assessment， and control". Based on seven anatomical sites， including nasal， ocular， and oral mucosa， a stratified monitoring system was constructed. The guideline proposed key recommendations on improving package insert sections such as "Adverse Reactions"， "Contraindications"， and "Precautions"， clinical procedure standardization in healthcare institutions， risk control， and dynamic pharmacovigilance. The Guideline provides evidence-based support tailored to the risk profile of Chinese patent medicines for mucosal administration， filling the current gap in international pharmacovigilance standards in this field， while offering technical support for safety management across the full life cycle of medicines for mucosal administration.

Objective:To evaluate the safety and efficacy of secondary transport on extracorporeal membrane oxygenation (ECMO) for critically ill children.Methods:This was a retrospective cohort study. Data from 222 pediatric patients who underwent ECMO transport from May 2019 to May 2024 at 5 ECMO centers and Chinese Database of Pediatric Extracorporeal Life Support Organization were collected. The cases were divided into primary and secondary transport groups by nature of transport. The clinical data, including demographics, ECMO indications, transport distance, pre-transport lab results, prognosis and complications were analyzed. Two independent samples t-test, Wilcoxon test, and χ2 test or Fisher′s exact probability method were used to compare the differences between 2 groups and evaluate the safety and efficacy of secondary transport. Results:Among the 222 children transported with ECMO, there were 135 males and 87 females, with an age of 3.0 (0.2, 7.0) years. There were 202 cases in the primary transport group and 20 cases in the secondary transport group. All secondary transport patients had failed attempts at weaning ECMO before transfer. The patients in the secondary transport group were older, had higher rates of surgical cannulation, circulatory support, and pre-ECMO lactate levels compared to the primary transport group (7.0 (2.8, 10.0) vs. 3.0 (0.2, 6.0) years old, 55.0% (11/20) vs. 3.6% (7/202), 80.0% (16/20) vs. 41.6% (84/202), (10±4) vs. (7±6) mmol/L, Z=3.41, χ 2=66.31, 10.99, t=2.24, all P<0.05). In the secondary transport group, the vasoactive-inotropic scores of patients on circulatory support and the oxygenation index for patients requiring respiratory support were higher than those in the primary transport group (83±33 vs. 82±68, 51.0±1.8 vs. 37.4±10.2, t=2.36, 2.63, respectively; both P<0.05). There were no statistically significant differences between the 2 groups in sex, transport distance, pre-ECMO creatinine, arterial blood gas BE values, and ECMO duration (all P>0.05). No life-threatening complications occurred during the transport in either group. Two patients in the secondary transport group underwent heart transplantation, and 1 patient underwent radiofrequency ablation. The overall survival rate between the 2 groups showed no statistically significant difference (45.0% (9/20) vs. 55.4% (112/202), χ2=1.15, P>0.05). Conclusions:Secondary ECMO transport for critically ill children don't increase mortality or life-threatening complications during transport. ECMO patients who cannot receive effective treatment locally can benefit from secondary transport to an advanced ECMO center provides further treatment opportunities.

Objective To explore the clinical value of energy-spectrum CT single-energy imaging in enhancing the image quality and stent display of stent placement CT angiography(CTA)in lower extremity atherosclerotic occlusive disease.Methods Twenty patients[mean(65.61±9.65)years;male/female,16/4]who underwent stenting for chronic occlusive disease of the lower extremity arteries by lower extremity arterial energetic spectral CTA were retrospectively recruited at our hospital.The original images were reconstructed into seven sets of single energy(40-100 keV),120 kVp,virtual unenhanced images(VUE)and metal artifact reduction(MAR)technique images.Images were debossed and then scaffolded for display with volumetric reconstruction(VR),maximum density projection(MIP)and curve planar reconstruction(CPR),and were objectively and subjectively assessed and compared using one-way analysis of variance(ANOVA).Results The 80 keV and MAR images had the highest scores compared to the other reconstruction group images(P＜0.01).Conclusion 80 keV single-energy imaging and de-metallization artifacts MAR improve the image quality of lower extremity arterial stent lumen and structure display;therefore,they have higher diagnostic value for clinicians.

This study aims to investigate whether the dietary supplement coenzyme Q10(CoQ10)alleviates bisphenol A(BPA)-induced mouse Leydig cell line(TM3)damage through autophagy pathway.Cell activity was measured by CCK-8 assay when treated with different concentrations of BPA for 24 h.TM3 cells were then divided into 5 groups:CON group,BPA group,Torin2 group,CQ group and BPA+CoQ10 group,with three repeats in each group.The morphology of TM3 cells were observed under inverted light microscope.Western blot was used to determine the protein ex-pression of p62 and LC3-Ⅰ/Ⅱ.The autophagy level of TM3 cells was detected by MDC cell auto-phagy staining,the mRNA expression levels of Atg7,Beclin 1,p62 and Atg5 genes were deter-mined by RT-qPCR,and the apoptosis rate of TM3 cells was detected by flow cytometry.The results showed that compared with 0 μmol/L BPA treatment group,the viability of TM3 cells de-creased significantly after 24 h treatment with 60 μmol/L BPA(P＜0.01).Compared with CON group,the number of TM3 cells markedly reduced in the BPA-treated group,the expression of au-tophagy-related proteins(p62,LC3-Ⅱ)significantly increased(P＜0.01),comparable to the CQ group.The MDC fluorescence intensity dramatically enhanced(P＜0.01),the mRNA expression levels of autophagy-related genes(Atg7,Beclin1,p62,Atg5)significantly elevated(P＜0.01),and the apoptosis rate significantly increased(P＜0.01).Compared with BPA group,the expression levels of autophagy-related genes Atg7 and Beclin1 mRNA(P＜0.05),p 62 and Atg5 mRNA(P＜0.01)in TM3 cells treated with BPA+CoQ10 significantly decreased.Moreover,the expres-sion levels of autophagy-related protein p62(P＜0.01)and LC3-Ⅱ(P＜0.05),MDC fluorescence intensity(P＜0.05)and apoptosis rate(P＜0.01)also markedly reduced.In conclusion,CoQ10 could subsequently reduce the apoptosis of TM3 cells by improving the abnormal autophagy flux induced by BPA.

Objective To validate the diagnostic performance and risk stratification ability of an AI-based recognition system(PE-AI)for pulmonary embolism(PE)using computed tomography pulmonary angiography(CTPA)so as to analyze its diagnostic value in clinical practice.Methods A total of 416 patients with suspected PE who underwent CTPA from January 1,2023 to December 10,2023 at our hospital were included in this study.Two junior radiologists and PE-AI separately detected and diagnosed emboli in the collected cases by double-blind method,and recorded the diagnosis time respectively.Three senior radiologists reviewing with clinical follow-up results were used as the gold standard in this study.Diagnostic performance was evaluated by using the receiver operating characteristic(ROC)curve analysis and Delong-t test.For positive cases,the pulmonary artery obstruction index(PAOI)calculated by AI and manually were collected respectively and consistency analysis was performed.Results The area under the curve(AUC)of PE-AI,manual and combined diagnosis was 85.6％,90.8％and 95.1％,respectively,which differed significantly(P＜0.05).The reading time of PE-AI[(0.16±0.07)min]was significantly lower than the time of manual[(4.42±1.85)min,P＜0.001]and combined diagnosis[(4.58±1.84)min,P＜0.001].The PAOI measured by PE-AI and manually had high consistency(intraclass correlation efficient,ICC=0.80)in the subgroup analysis of confirmed cases.Conclusion AI can quickly identify pulmonary artery emboli in a short time and assist radiologists to improve diagnostic efficiency.At the same time,through the intelligent detection of PAOI,it is helpful for the risk stratification of patients with PE and optimizing the diagnosis and treatment pathway for pulmonary embolism.

BACKGROUND:Diffuse idiopathic skeletal hyperostosis is a systemic,non-inflammatory disease characterized by calcification and ossification of ligaments,tendons,and their attachments,predominantly affecting men over the age of 50.Studies have shown a higher prevalence of diffuse idiopathic skeletal hyperostosis among obese individuals;however,the causal relationship between the two remains unclear.OBJECTIVE:To investigate the causal relationship between obesity and diffuse idiopathic skeletal hyperostosis using Mendelian randomization analysis.METHODS:The study utilized single nucleotide polymorphisms from the Genome Wide Association Study database as instrumental variables,incorporating data related to obesity and diffuse idiopathic skeletal hyperostosis.A bidirectional two-sample Mendelian randomization analysis was performed to assess the causal relationship between obesity and diffuse idiopathic skeletal hyperostosis,with evaluations for pleiotropy,heterogeneity,and sensitivity.RESULTS AND CONCLUSION:The Mendelian randomization analysis revealed a significant positive causal relationship between obesity and diffuse idiopathic skeletal hyperostosis.The inverse-variance weighted method indicated that"obesity"(odds ratio[OR]=1.111,95%confidence interval[CI]:1.068-1.156,P=1.598×10-7),"obesity due to excess calories"(OR=1.093,95%CI:1.042-1.146,P=0.000),and"obesity,other/unspecified"(OR=1.109,95%CI:1.069-1.152,P=4.908×10-8)were significantly associated with diffuse idiopathic skeletal hyperostosis.Conversely,the reverse Mendelian randomization analysis did not find a causal relationship between diffuse idiopathic skeletal hyperostosis and obesity.The robustness of the Mendelian randomization analysis results was confirmed by pleiotropy,heterogeneity and sensitivity tests,indicating that while obesity significantly increases the risk of diffuse idiopathic skeletal hyperostosis,but diffuse idiopathic skeletal hyperostosis does not pose a risk factor for obesity.

Objective To explore the clinical value of energy-spectrum CT single-energy imaging in enhancing the image quality and stent display of stent placement CT angiography(CTA)in lower extremity atherosclerotic occlusive disease.Methods Twenty patients[mean(65.61±9.65)years;male/female,16/4]who underwent stenting for chronic occlusive disease of the lower extremity arteries by lower extremity arterial energetic spectral CTA were retrospectively recruited at our hospital.The original images were reconstructed into seven sets of single energy(40-100 keV),120 kVp,virtual unenhanced images(VUE)and metal artifact reduction(MAR)technique images.Images were debossed and then scaffolded for display with volumetric reconstruction(VR),maximum density projection(MIP)and curve planar reconstruction(CPR),and were objectively and subjectively assessed and compared using one-way analysis of variance(ANOVA).Results The 80 keV and MAR images had the highest scores compared to the other reconstruction group images(P＜0.01).Conclusion 80 keV single-energy imaging and de-metallization artifacts MAR improve the image quality of lower extremity arterial stent lumen and structure display;therefore,they have higher diagnostic value for clinicians.

This study aims to investigate whether the dietary supplement coenzyme Q10(CoQ10)alleviates bisphenol A(BPA)-induced mouse Leydig cell line(TM3)damage through autophagy pathway.Cell activity was measured by CCK-8 assay when treated with different concentrations of BPA for 24 h.TM3 cells were then divided into 5 groups:CON group,BPA group,Torin2 group,CQ group and BPA+CoQ10 group,with three repeats in each group.The morphology of TM3 cells were observed under inverted light microscope.Western blot was used to determine the protein ex-pression of p62 and LC3-Ⅰ/Ⅱ.The autophagy level of TM3 cells was detected by MDC cell auto-phagy staining,the mRNA expression levels of Atg7,Beclin 1,p62 and Atg5 genes were deter-mined by RT-qPCR,and the apoptosis rate of TM3 cells was detected by flow cytometry.The results showed that compared with 0 μmol/L BPA treatment group,the viability of TM3 cells de-creased significantly after 24 h treatment with 60 μmol/L BPA(P＜0.01).Compared with CON group,the number of TM3 cells markedly reduced in the BPA-treated group,the expression of au-tophagy-related proteins(p62,LC3-Ⅱ)significantly increased(P＜0.01),comparable to the CQ group.The MDC fluorescence intensity dramatically enhanced(P＜0.01),the mRNA expression levels of autophagy-related genes(Atg7,Beclin1,p62,Atg5)significantly elevated(P＜0.01),and the apoptosis rate significantly increased(P＜0.01).Compared with BPA group,the expression levels of autophagy-related genes Atg7 and Beclin1 mRNA(P＜0.05),p 62 and Atg5 mRNA(P＜0.01)in TM3 cells treated with BPA+CoQ10 significantly decreased.Moreover,the expres-sion levels of autophagy-related protein p62(P＜0.01)and LC3-Ⅱ(P＜0.05),MDC fluorescence intensity(P＜0.05)and apoptosis rate(P＜0.01)also markedly reduced.In conclusion,CoQ10 could subsequently reduce the apoptosis of TM3 cells by improving the abnormal autophagy flux induced by BPA.

Objective To validate the diagnostic performance and risk stratification ability of an AI-based recognition system(PE-AI)for pulmonary embolism(PE)using computed tomography pulmonary angiography(CTPA)so as to analyze its diagnostic value in clinical practice.Methods A total of 416 patients with suspected PE who underwent CTPA from January 1,2023 to December 10,2023 at our hospital were included in this study.Two junior radiologists and PE-AI separately detected and diagnosed emboli in the collected cases by double-blind method,and recorded the diagnosis time respectively.Three senior radiologists reviewing with clinical follow-up results were used as the gold standard in this study.Diagnostic performance was evaluated by using the receiver operating characteristic(ROC)curve analysis and Delong-t test.For positive cases,the pulmonary artery obstruction index(PAOI)calculated by AI and manually were collected respectively and consistency analysis was performed.Results The area under the curve(AUC)of PE-AI,manual and combined diagnosis was 85.6％,90.8％and 95.1％,respectively,which differed significantly(P＜0.05).The reading time of PE-AI[(0.16±0.07)min]was significantly lower than the time of manual[(4.42±1.85)min,P＜0.001]and combined diagnosis[(4.58±1.84)min,P＜0.001].The PAOI measured by PE-AI and manually had high consistency(intraclass correlation efficient,ICC=0.80)in the subgroup analysis of confirmed cases.Conclusion AI can quickly identify pulmonary artery emboli in a short time and assist radiologists to improve diagnostic efficiency.At the same time,through the intelligent detection of PAOI,it is helpful for the risk stratification of patients with PE and optimizing the diagnosis and treatment pathway for pulmonary embolism.