OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of deucravacitinib in the treatment of moderate- to-severe plaque psoriasis. METHODS Rapid health technology assessment （HTA） reports， systematic reviews （SR）/meta- analyses， and pharmacoeconomic studies on deucravacitinib for the treatment of moderate-to-severe plaque psoriasis were identified by searching PubMed， Web of Science， Embase， CNKI， Wanfang data and official HTA websites. The search time frame spanned from database inception to July 2025. After literature screening， data extraction， and quality assessment， the study results were subjected to descriptive analysis and synthesis. RESULTS A total of 14 articles were finally included， consisting of 1 HTA report， 10 SR/meta-analyses， and 3 pharmacoeconomic studies. Regarding efficacy， deucravacitinib demonstrated superior efficacy to both placebo and apremilast， with significantly higher response rates for Psoriasis Area and Severity Index 50/75/90/100， Static Physician’ s Global Assessment 0/1， and Dermatology Life Quality Index 0/1， as well as greater reduction in Psoriasis Symptoms and Signs Diary Score （P＜0.05）. Regarding safety， deucravacitinib was well-tolerated. Although the overall incidence of adverse events （AEs） was higher than placebo， it was not significantly different from apremilast. Moreover， the incidence of serious AEs and the rate of discontinuation due to AEs did not differ significantly from placebo （P＞0.05）. Regarding cost-effectiveness， deucravacitinib proved to be more cost-effective than apremilast across multiple healthcare system perspectives， including those of the United States， Japan， and China. CONCLUSIONS Deucravacitinib exhibits favorable efficacy， safety， and cost-effectiveness in the treatment of moderate-to-severe plaque psoriasis. Additional real-world studies are warranted to further refine its evaluation.

ObjectiveTo establish an animal model of atrial fibrillation（AF） that accurately reflects the phlegm-heat and blood stasis（TRYZ） pathogenesis in traditional Chinese medicine. MethodsForty SPF-grade SD rats were randomly assigned using a random number table to the following groups：the control group， the TRYZ+AF group，the AF group and the TRYZ group， with ten rats in each group. The TRYZ+AF and TRYZ groups underwent a high-fat diet combined with intraperitoneal lipopolysaccharide（LPS） injection to simulate the pathological alterations of TRYZ syndrome. Groups TRYZ+AF and AF were induced with acetylcholine-calcium chloride（Ach-CaCl₂） via caudal vein injection to induce AF. The control group received no intervention and was maintained under normal conditions. The modeling period lasted 3 weeks. Electrocardiography was used to assess AF episodes and duration， echocardiography evaluated left atrial dimensions and cardiac function， fully automated biochemical analyzer measured the levels of total cholesterol（TC）， triglycerides（TG）， high-density lipoprotein cholesterol（HDL-C） and low-density lipoprotein cholesterol（LDL-C）， hemoreometer analyzed the whole blood viscosity， plasma viscosity， and whole blood reduced viscosity， a coagulation analyzer assessed prothrombin time（PT）， activated partial thromboplastin time（APTT）， thrombin time（TT）， and fibrinogen（FIB）， enzyme-linked immunosorbent assay（ELISA） was used to determine the levels of C-reactive protein（CRP）， interleukin（IL）-1β， IL-6， IL-17， tumour necrosis factor（TNF）-α， matrix metalloproteinase-9（MMP-9）， galectin-3（Gal-3）， Collagen Ⅰ， and α-smooth muscle actin（α-SMA）. Hematoxylin-eosin（HE） staining and Masson's trichrome staining were used to analyze pathological changes in atrial myocardium， Western blot was employed to detect MMP-9， Collagen Ⅰ and α-SMA protein expression in myocardial tissue， real-time quantitative polymerase chain reaction（Real-time PCR） evaluated fibrous factor gene expression levels. Changes in the TRYZ syndrome were assessed via body weight， tongue color［red（R）， green（G）， and blue（B）］， and rectal temperature. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was employed to detect differential metabolites between the control group and the TRYZ+AF group. ResultsFollowing three weeks of sustained modeling， compared with the control group， rats in the TRYZ+AF and the TRYZ groups exhibited reduced body weight， dry faeces， elevated rectal temperature， dark red tongue， decreased RGB values on the tongue surface， and markedly elevated TC and LDL-C levels（P<0.05， P<0.01）. The TRYZ+AF， TRYZ， and AF groups exhibited significantly decreased TT， APTT and PT， along with markedly elevated whole blood viscosity and FIB（P<0.05， P<0.01）. Rats in the TRYZ+AF and AF groups exhibited AF rhythm， markedly decreased heart rate， prolonged RR intervals， enlarged left atrium， and significantly reduced ejection fraction and shortening fraction（P<0.05， P<0.01）. Serum levels of CRP， IL-1β， IL-6， IL-17， TNF-α， MMP-9， Gal-3， Collagen Ⅰ， and α-SMA were elevated in rats from the TRYZ+AF， TRYZ， and AF groups compared to the control group， with the most pronounced increase observed in the TRYZ+AF group（P<0.05， P<0.01）. Histopathology revealed that the collagen fiber deposition in the atrial of rats in the TRYZ+AF， TRYZ and AF groups was higher than that in the control group（P<0.05， P<0.01）. Western blot and Real-time PCR results further demonstrated that the protein and mRNA expression levels of MMP-9， Collagen Ⅰ and α-SMA in the myocardial tissue of the TRYZ+AF group were higher than those in the other three groups（P<0.05， P<0.01）. Metabolomic analysis revealed 173 differentially expressed metabolites in the TRYZ+AF group and the control group， primarily enriched in pathways such as glycerophospholipid metabolism and glycolysis/gluconeogenesis. ConclusionThis study successfully establishes a rat model of AF integrated with the TRYZ syndrome， demonstrating the pathological process where the interactions of phlegm， heat and stasis jointly trigger tremor， this provides a reliable experimental tool for in-depth research into the biological basis of this disease syndrome.

ObjectiveTo investigate the effect and mechanism of transplantation of human umbilical cord mesenchymal stem cell （hUC-MSC） with overexpression of the Numb gene in the treatment of cholestatic liver fibrosis （CLF）. MethodsThe technique of lentiviral transfection was used to induce the overexpression of the Numb gene in hUC-MSC （hUC-MSC^Numb-OE）， and hUC-MSC transfected with empty vector （hUC-MSC^OE-EV） was used as negative control. Bile duct ligation （BDL） was performed to establish a rat model of CLF， and then the rats were randomly divided into BDL group， hUC-MSC group， hUC-MSC^OE-EV group， and hUC-MSC^Numb-OE group， while a sham-operation group was also established. The rats in the intervention groups were given a single splenic injection of the corresponding cells after BDL， and samples were collected at the end of week 4. Related indicators were measured， including serum biochemistry， liver histopathology， the content of hydroxyproline （Hyp） in the liver， hepatic stellate cell activation， ductular reaction， liver regeneration， and the expression levels of key molecules in the Numb-p53 signaling axis. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the BDL group， the hUC-MSC group and the hUC-MSC^OE-EV group had significant reductions in the levels of serum biochemical parameters （aspartate aminotransferase， gamma-glutamyl transpeptidase， total bile acid， total bilirubin， and direct bilirubin）， liver fibrosis markers （the content of Hyp and the expression levels of alpha-smooth muscle actin， tumor necrosis factor-α， and transforming growth factor-beta 1）， and ductular reaction markers （the expression levels of CK7 and CK19） （all P <0.05）， and compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significantly greater improvements in the above indicators （all P <0.05）. In addition， compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significant improvements in the expression levels of liver regeneration-related markers （albumin and hepatocyte nuclear factor 4α） and the molecules associated with the Numb-p53 signaling axis （Numb， pNumb， Mdm2， and p53） （all P <0.05）. ConclusionOverexpression of the Numb gene can enhance the therapeutic effect of hUC-MSC on CLF， possibly by activating the Numb-PTB^L-p53-HNF4α axis， promoting the hepatic differentiation of hUC-MSCs and subsequently enhancing liver regeneration.

Informed consent constitutes a fundamental ethical principle in medical practice. With the in-depth integration of generative artificial intelligence （AI） represented by Chat Generative Pre-trained Transformer （ChatGPT） with medicine， it has brought revolutionary development to traditional informed consent while also introducing new ethical challenges. ChatGPT offers features such as improving the readability of informed consent content， enhancing its comprehensiveness and accuracy， and increasing the convenience of obtaining informed consent. However， as the application of ChatGPT in informed consent is still in the exploratory stage， it is imperative to proactively and fully consider the accompanying ethical issues， such as information security， liability determination， transparency， and fairness. This paper conducted an ethical analysis on the challenges faced by generative AI， represented by ChatGPT， in the application of informed consent and proposed countermeasures， such as upholding free and fully informed consent， strengthening the balance of rights and obligations in informed consent， and establishing a transparent and fair supervision mechanism. The aim was to promote the ethically compliant， orderly， and controllable development of generative AI in the field of medical informed consent.

Objective To understand the utilization of immunization program vaccines in Liaoning Province and evaluate the vaccine management mode, and to provide a scientific basis for optimizing immunization strategies. Methods The vaccine collection data and vaccine administration data of vaccination units (including obstetric clinics) in the province from 2021 to 2024 were collected, and the vaccine utilization rate of immunization program was calculated. SPSS 13.0 software was used for data analysis, and χ² test was used for comparison. A two-sided P value of <0.05 was considered statistically significant. Results (1) From 2021 to 2024, vaccination units and obstetric clinics received a total of 15 993 884 doses of immunization program vaccines, with a total utilization rate of 79.34%. The highest utilization rate was the single-dose vaccine MPSV-AC (94.02%), followed by JE-L (91.92%). The lowest rate of use was the 5-dose strength vaccine MPSV-A (48.12%), followed by the 4-dose strength vaccine DT (63.13%). (2) Comparing MPSV-A and DT in different years, the utilization rate of MPSV-A and DT was the highest in 2021, 59.53% and 67.71%, respectively. From 2021 to 2024, the utilization rate of MPSV-A had a decreasing trend year by year, with the lowest being 38.65% (2024), and the loss coefficient of MPSV-A in each year was higher than that of DT. (3) Comparison of vaccine utilization rates in immunization programs around 2020, the utilization rate of single-dose vaccines increased significantly compared with before, while the utilization rate of multi-dose vaccines decreased compared with before 2020. Conclusion After 2020, the vaccine utilization rate of the immunization program in Liaoning Province has increased significantly, and the optimized vaccine management strategies has achieved remarkable results. Multi-dose vaccines remain highly susceptible to formulation-related factors and vaccination density. It is recommended to formulate precise vaccination strategies to reduce the loss of multi-dose vaccines.

ObjectiveTo investigate the therapeutic mechanism of Danhe granules in treating mixed hyperlipidemia based on network pharmacology， as well as animal and cell experiments. MethodsThe active compounds and targets of Danhe granules were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Encyclopedia of Traditional Chinese Medicine （ETCM）. Related targets for mixed hyperlipidemia were obtained from the GeneCards database. The intersecting targets were subjected to Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. A high-fat model was established in human hepatocellular carcinoma cells （HepG2） induced by palmitic acid （PA）， followed by intervention with Danhe granules to assess intracellular lipid accumulation and oxidative stress levels. A mixed hyperlipidemia rat model was also established and divided into low-， medium-， and high-dose Danhe granules groups （1.134， 2.268， and 4.536 g·kg^-1， respectively）， as well as a positive control group treated with pravastatin sodium （4.020 mg·kg^-1）. After eight weeks of intervention， serum lipid levels， inflammatory factors， oxidative stress indices， and the expression of key hepatic lipid metabolism-related proteins were determined. ResultsNetwork pharmacology identified 93 intersecting targets between Danhe granules and mixed hyperlipidemia， with peroxisome proliferator-activated receptor gamma （PPARG）， peroxisome proliferator-activated receptor alpha （PPARA）， tumor necrosis factor （TNF）， interleukin-6 （IL-6）， and IL-1B among the key nodes. The PPAR signaling pathway， AGE/RAGE signaling pathway， lipid metabolism， atherosclerosis and non-alcoholic fatty liver disease （NAFLD） were among the most significantly enriched pathways. Cellular experiments demonstrated that Danhe granules significantly reduced reactive oxygen species （ROS） and malondialdehyde （MDA） levels while increasing catalase （CAT） activity （P<0.05）， thereby alleviating intracellular lipid accumulation and triglyceride （TG） content in HepG2. In animal experiments， Danhe granules markedly decreased serum total cholesterol （TC）， TG， and low-density lipoprotein cholesterol （LDL-C） levels （P<0.05）， reduced hepatic MDA levels， and elevated superoxide dismutase （SOD） and CAT levels. Histological analysis showed alleviation of hepatic steatosis， upregulation of hepatic PPARA and lipoprotein lipase （LPL） expressions， and downregulation of sterol regulatory element-binding protein 1 （SREBP1） expression （P<0.05， P<0.01）. ConclusionDanhe granules improve lipid metabolism disorders in mixed hyperlipidemia by reducing MDA levels， enhancing SOD and CAT activities， scavenging excessive ROS， inhibiting oxidative stress， and mitigating liver injury. The underlying mechanism may involve the upregulation of PPARA and LPL and the suppression of SREBP1 expression.

ObjectiveTo investigate the therapeutic mechanism of Danhe granules in treating mixed hyperlipidemia based on network pharmacology， as well as animal and cell experiments. MethodsThe active compounds and targets of Danhe granules were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Encyclopedia of Traditional Chinese Medicine （ETCM）. Related targets for mixed hyperlipidemia were obtained from the GeneCards database. The intersecting targets were subjected to Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. A high-fat model was established in human hepatocellular carcinoma cells （HepG2） induced by palmitic acid （PA）， followed by intervention with Danhe granules to assess intracellular lipid accumulation and oxidative stress levels. A mixed hyperlipidemia rat model was also established and divided into low-， medium-， and high-dose Danhe granules groups （1.134， 2.268， and 4.536 g·kg^-1， respectively）， as well as a positive control group treated with pravastatin sodium （4.020 mg·kg^-1）. After eight weeks of intervention， serum lipid levels， inflammatory factors， oxidative stress indices， and the expression of key hepatic lipid metabolism-related proteins were determined. ResultsNetwork pharmacology identified 93 intersecting targets between Danhe granules and mixed hyperlipidemia， with peroxisome proliferator-activated receptor gamma （PPARG）， peroxisome proliferator-activated receptor alpha （PPARA）， tumor necrosis factor （TNF）， interleukin-6 （IL-6）， and IL-1B among the key nodes. The PPAR signaling pathway， AGE/RAGE signaling pathway， lipid metabolism， atherosclerosis and non-alcoholic fatty liver disease （NAFLD） were among the most significantly enriched pathways. Cellular experiments demonstrated that Danhe granules significantly reduced reactive oxygen species （ROS） and malondialdehyde （MDA） levels while increasing catalase （CAT） activity （P<0.05）， thereby alleviating intracellular lipid accumulation and triglyceride （TG） content in HepG2. In animal experiments， Danhe granules markedly decreased serum total cholesterol （TC）， TG， and low-density lipoprotein cholesterol （LDL-C） levels （P<0.05）， reduced hepatic MDA levels， and elevated superoxide dismutase （SOD） and CAT levels. Histological analysis showed alleviation of hepatic steatosis， upregulation of hepatic PPARA and lipoprotein lipase （LPL） expressions， and downregulation of sterol regulatory element-binding protein 1 （SREBP1） expression （P<0.05， P<0.01）. ConclusionDanhe granules improve lipid metabolism disorders in mixed hyperlipidemia by reducing MDA levels， enhancing SOD and CAT activities， scavenging excessive ROS， inhibiting oxidative stress， and mitigating liver injury. The underlying mechanism may involve the upregulation of PPARA and LPL and the suppression of SREBP1 expression.

ObjectiveZheng’s San Qi San (ZSQS) power, a classic traditional Chinese medicine (TCM) formula, is used for treating soft tissue injuries involving muscles, tendons, and ligaments. However, its underlying therapeutic mechanisms remain unclear. This study aimed to screen and identify pharmaceutically active ingredients and their candidate biomolecule targets, and further elucidate the molecular mechanism of ZSQS in the treatment of skeletal muscle injury. MethodsNetwork pharmacology was employed to construct “ZSQS-component-target”, “protein-protein interaction (PPI)” and “active ingredient-core protein-pathway” networks to predict the key active ingredients and potential core targets of ZSQS for skeletal muscle injury. The predicted results were then validated via microarray data from the GEO database. Molecular docking was then performed to assess the binding ability between the screened active ingredients of ZSQS and the candidate core targets. Moreover, liquid chromatography-mass spectrometry (LC-MS) was used for qualitative and quantitative analysis to verify the active components of the drug and ZSQS serum. Finally, an animal model of eccentric exercise-induced skeletal muscle injury and a myotube cell model of oxidative stress-induced injury were established to validate the effects of ZSQS and its interventional effects on the biological functions of critical targets, thereby demonstrating the potential therapeutic mechanism of ZSQS. ResultsAmong the 111 active components identified in ZSQS and their corresponding 204 targets related to the skeletal muscle injury repair process, 14 core targets (including AKT1) and 4 core active components (quercetin, luteolin, kaempferol, and β‑sitosterol) were screened out, while the corresponding metabolites of quercetin, luteolin and kaempferol were detected in the ZSQS serum. Among these targets, 5 candidate genes (IL-6, CASP3, HIF1A, STAT3, and JUN) overlapped with the differential expression screening results with GEO data, and IL-6 was confirmed to be enriched in the PI3K/AKT pathway. Combined with the prediction results of the AKT expression levels, these findings suggest that the phosphorylation level of AKT1 plays a core role in the therapeutic mechanism of ZSQS. Molecular docking analysis further revealed that the PH domain of AKT1 had high binding energy with all 4 core active components, as verified by LC-MS. Finally, animal model studies have shown the promoting effect of ZSQS administration on skeletal muscle injury repair and its possible antioxidant damage mechanism. Cell model studies further demonstrated that ZSQS-containing serum, core active ingredient combination therapy, and quercetin monomer could increase the phosphorylation level of AKT, promote the nuclear translocation of Nrf2, upregulate the expression of downstream antioxidant enzymes (SOD, GPx, and GR), and inhibit the expression of inflammatory factors (IL-6 and TNF-α), thereby alleviating oxidative stress and the inflammatory response. ConclusionZSQS alleviates skeletal muscle injury mainly by activating the AKT/Nrf2 signaling pathway, enhancing cellular antioxidant and anti-inflammatory capabilities. The results of this study provide a scientific basis for the clinical application and modernized development of ZSQS.

ObjectiveTo observe the effect of M1 bone marrow-derived macrophages （M1-BMDM） with Wnt5a knockdown on liver fibrosis and regeneration in a rat model of liver cirrhosis， and to investigate its gain-of-function effect compared with unmodified M1-BMDM. MethodsPrimary bone marrow-derived macrophages were isolated from rats and were polarized to M1 phenotype to construct M1-BMDM^Wnt5a-KD cells. A rat model of liver cirrhosis induced by CCl₄/2-AAF was established， and at the end of week 8， rats were randomly divided into model group， M1-BMDM group， M1-BMDM Wnt5a-knockdown empty vector group （M1-BMDM^KD-EV group）， and M1-BMDM Wnt5a-knockdown group （M1-BMDM^Wnt5a-KD group）， with 6 rats in each group. On the first day of week 9， the rats in each group were given a single injection of the corresponding cells via the caudal vein， along with an intraperitoneal injection of a CCR2 inhibitor. Six rats without any treatment were used as normal control group. Samples were collected at the end of week 12 to assess liver histopathology， serum liver function parameters， hepatic stellate cell activation， and the expression levels of mature hepatocyte markers. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group， all cell treatment groups had significant alleviation of liver inflammatory response and significant reductions in the activities of alanine aminotransferase and aspartate aminotransferase （AST） in serum （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly lower serum level of AST than the M1-BMDM group （P<0.05）. The semi-quantitative analysis based on immunohistochemical staining showed that compared with the model group， all cell treatment groups had a significant reduction in the percentage of CD68-positive area （all P<0.05）， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had a significant reduction in the percentage of CD68-positive area and a significant increase in the percentage of CD163-positive area （both P<0.05）. Compared with the model group， all cell treatment groups had significant reductions in the mRNA expression levels of CD68 and tumor necrosis factor-α （all P<0.05） and the protein expression level of CD68 （all P<0.01）； compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant increases in the protein and mRNA expression levels of CD163 （both P<0.05）， significant reductions in the protein and mRNA expression levels of CD68 （both P<0.05）， and a significant reduction in the protein expression level of tumor necrosis factor-α （P<0.01）. Sirius Red collagen staining and alpha-smooth muscle actin （α-SMA） immunohistochemical staining showed that compared with the model group， all cell treatment groups had significant alleviation of liver collagen deposition and α-SMA-positive area， with the most significant changes in the M1-BMDM^Wnt5a-KD group， and compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significantly smaller Sirius Red-positive area and α-SMA-positive area and a significantly lower content of hydroxyproline in liver tissue （all P<0.05）. Compared with the M1-BMDM^KD-EV group， the M1-BMDM^Wnt5a-KD group had significant reductions in the protein and mRNA expression levels of α-SMA and the mRNA expression level of COL-I and TGF-β （all P<0.05）. Compared with the model group， all cell treatment groups had a significant increase in the protein expression level of HNF-4α in liver tissue （all P<0.05）， and the M1-BMDM^Wnt5a-KD group had significantly higher protein and mRNA expression levels of HNF-4α and hepatocyte specific antigen than the M1-BMDM^KD-EV group （both P<0.05）. The M1-BMDM^Wnt5a-KD group had a significantly higher serum level of albumin than the M1-BMDM^KD-EV group （P<0.01）. Immunofluorescence co-staining showed that compared with the model group， all cell treatment groups had a significant increase in the number of cells stained positive for HNF and HNF-4α and Ki67 （all P<0.01）， and the M1-BMDM^Wnt5a-KD group had a significantly higher number of such cells than the M1-BMDM^KD-EV group （P<0.05）. ConclusionInhibition of Wnt5a expression enhances the therapeutic effect of M1-BMDM on rats with liver cirrhosis induced by CCl₄/2-AAF， which provides new ideas for enhancing the anti-cirrhotic effect of M1-BMDM through genetic modification.

Hepatic fibrosis is a reversible pathological process in various chronic liver diseases and is closely associated with the development and progression of severe liver diseases such as liver cirrhosis and hepatocellular carcinoma， and it has emerged as a significant global health challenge. In recent years， studies have shown that histone lactylation， a newly discovered epigenetic modification， actively participates in regulating the progression of hepatic fibrosis. This article systematically reviews the core regulatory effect of histone lactylation modification in the interaction between inflammatory microenvironment and hepatic fibrosis， in order to clarify the cascade regulatory mechanism of “inflammation-hepatic fibrosis” and provide new insights for early diagnosis， targeted intervention， and prevention of malignant transformation in hepatic fibrosis.