Chronic liver diseases are a group of diseases in which the liver is subjected to a variety of injuries over a long period of time， resulting in irreversible pathological changes that last longer than 6 months. Emodin （EMO） is a natural anthraquinone derivative derived from Rheum officinale， and its pharmacological effect has been extensively studied， exhibiting a variety of biological properties and involving multiple signaling molecules and pathways. Western medicine or surgical treatment is currently the main treatment regimen for chronic liver diseases， and the advance in treatment is limited by various reasons such as side effects and high costs. Due to its natural origin and efficacy， EMO has unique advantages in the treatment of chronic liver diseases and has now become a research hotspot. This article summarizes the therapeutic effect of EMO on chronic liver diseases and its mechanism， in order to provide a certain scientific basis for the traditional Chinese medicine treatment of chronic liver diseases and the development of drugs in clinical practice.

Objective To investigate the mechanism by which Guijianyu ameliorates podocyte injury in a mouse model of diabetic kidney disease(DKD)induced by advanced glycation endproducts(AGEs).Methods Sixty db/db mouse models of DKD were randomized equally into 5 groups for treatment with saline,Guijianyu extract at 3 doses or irbesartan for 12 weeks,and the changes in renal pathology and structure were observed using transmission electron microscopy,and the expressions of related genes and key proteins were detected using RT-qPCR and immunohistochemistry.In cultured MPC-5 cells incubated with 50 mg/L AGEs-BSA for 24 h,the effect of different concentrations of Guijianyu extract on cell viability was examined with CCK-8 assay;Western blotting was performed to detect the protein expressions of RAGE,VEGFA,TNF-α,NF-κB(p65),IL-6 and caspase-3,and the mRNA expressions of RAGE,NF-κB(p65),VEGFA and IL-6 were detected with RT-qPCR.Results In mouse models of DKD,treatment with high-dose Guijianyu extract significantly reduced renal expressions of RAGE,VEGFA,NF-κB(p65),and IL-6 proteins and the mRNA expressions of RAGE,NF-κB,and IL-6.In MPC-5 cells,exposure to AGEs significantly reduced cell viability and increased the protein expressions of RAGE,NF-κB(p65),VEGFA,TNF-α,IL-6 and caspase-3(P<0.05)and mRNA expressions of RAGE,NF-κB(p65),VEGFA,and IL-6.Treatment with Guijianyu extract obviously improved cell viability and reduced the expressions of RAGE,NF-κB(p65),VEGFA,TNF-α,IL-6,and caspase-3.Furthermore,Guijianyu extract effectively reversed RAGE agonist-induced elevation of protein expressions of RAGE,VEGFA,TNF-α,IL-6,and caspase-3 and mRNA expressions of RAGE,NF-κB(p65),IL-6,and VEGFA in MPC-5 cells.Conclusion Guijianyu extract ameliorates AGEs-induced mouse renal podocyte injury in DKD by inhibiting the activation of AGEs-RAGE signaling pathway and reducing the expressions of pro-inflammatory cytokines and vascular endothelial growth factors.

OBJECTIVE: To explore the regulatory mechanisms underlying the weak expression of ABO blood group antigens due to variants in the non-coding regions of the ABO gene. METHODS: From June 2014 to October 2023, a total of 29 samples from the Taiyuan Blood Center and local hospitals, which were serologically identified as having weak ABO antigen expression without detectable coding region mutations, were selected for this study. Full-length ABO gene sequencing was performed using third-generation long-read sequencing technology (Pacific Biosciences) to obtain complete haplotype sequences of the ABO gene. Variants in the non-coding regions were compared and identified to infer their regulatory effects on weak antigen expression. The procedures followed in this study were in accordance with the ethical standards of the World Medical Association's Declaration of Helsinki (2013 revision). The Medical Ethics Committee of Taiyuan Blood Center has granted an exemption from ethical review. RESULTS: 18 bp deletions in the -35 to -18 region of the promoter were identified in 7 samples. Variants in intron 1 (+5.8 kb) were detected in 7 samples, including ABO*A (28+5792_5793delCT (1 case) and ABO*B (28+5793T>C) located in the GATA binding region; ABO*B (28+5808C>T) (1 case) in the E-box region; and ABO*B (28+5875C>T) (4 cases) in the RUNX1 binding region. Nucleotide variants at splice sites were detected in 2 samples, namely ABO*B (C.98+1G>A) and ABO*B (C.204-2A>C). CONCLUSION Variants in the non-coding regulatory sequences of the ABO gene are a significant factor contributing to weak ABO antigen expression. In clinical ABO sequencing, it is essential to screen not only the conventional coding regions but also the flanking sequences, introns, and splice sites of the ABO gene to facilitate precise blood transfusion.
ABO Blood-Group System/genetics* ; Humans ; Alleles ; Promoter Regions, Genetic ; Haplotypes ; Introns

AIM To investigate the effects of Modified Baitouweng Decoction and Lizhong Decoction on mouse ulcerative colitis(UC).METHODS The mouse model of UC was established by 3％dextran sulfate sodium(DSS)induction.The C57BL/6 mice were randomly divided into the blank group,the model group,the low,medium and high dose Modified Baitouweng Decoction and Lizhong Decoction groups(3,6,12 g/kg),and sulfasalazine group(300 mg/kg),for 7 days gavage of the appropriate drugs,with 10 mice in each group.The mice had their disease activity index(DAI)and colonic mucosal damage index(CMDI)calculated;their colonic length and unit colonic weight measured;their histopathologic changes of colon observed by HE;their colonic ROS,MDA levels and GSH-Px,SOD activities detected by superoxide anion fluorescent probes and kits;their colonic levels of TNF-α,IL-6 and IL-1β detected by ELISA;their colonic LC3 expression detected by immunofluorescence method;and their colonic AMPK,mTOR and p70S6K protein expressions detected by Western blot method.RESULTS Compared with the blank group,the model group displayed significantly higher DAI score,CMDI score,unit colon weight,pathology score,ROS and MDA content,TNF-α,IL-6,and IL-1β levels,and mTOR and p70S6K protein expression(P＜0.01);and significantly lower colon length,GSH-Px and SOD activity,LC3 level,and phosphorylated AMPK protein expression(P＜0.01).Compared with the model group,the groups intervened with Modified Baitouweng Decoction and Lizhong Decoction or sulfasalazine shared decreased DAI score,CMDI score,unit colon mass,pathology score,ROS,MDA,TNF-α,IL-6,IL-1β levels,mTOR,p70S6K protein expressions(P＜0.01);and significantly improved symptomsin terms of the elevated colonic length,GSH-Px,SOD activities,LC3 level,AMPK protein expression(P＜0.01).CONCLUSION Modified Baitouweng Decoction and Lizhong Decoction may attenuate inflammatory response and oxidative damage in UC mouse models via AMPK/mTOR/p70S6K signaling pathway.

Objective:To explore the clinical value of computed tomography(CT)with three-dimensional(3D)reconstruction technique in diagnosis and selecting surgical methods for patients with pituitary tumor.Methods:A retrospective analysis was performed on the clinical data of 82 elderly patients with suspected pituitary tumor at Huanggang Central Hospital between January 2021 and December 2023.All of patients underwent CT examination with 3D reconstruction technique and MRI examination.The postoperatively pathological results were used as the golden standard to compare the diagnostic results and efficiency of CT with 3D reconstruction technique and MRI for pituitary tumor.The differences of the two examination methods were compared in images quality.The clinical value of CT with 3D reconstruction technique for the selection of surgical method was further analyzed.Results:In 82 elderly patients with suspected pituitary tumor,56 cases were confirmed by postoperatively pathological examination,and 49 cases were confirmed by CT with 3D reconstruction technique,and 60 cases were confirmed by MRI.The characteristics of CT imaging were:quasi-circular or circular tumors were the majority,which had clear boundaries,and tumors grew to the side of sella turcica and around of the sella turcica,which accompanied by enlarged pituitary fossa.MRI imaging characteristics of pituitary tumors were as follows:the most of them accompanied with equal T1 and slightly high T2 signals,and there was enhancement of obvious ring,and the snowman sign.There was no significant difference in diagnostic accuracy between CT with 3D reconstruction technique and MRI(P>0.05).The diagnostic specificity of CT with 3D reconstruction technique was 96.15%,which was higher than 76.92%of MRI,while its sensitivity was 85.71%,which was lower than 96.43%of MRI,and the differences were statistically significant(x2=4.413,3.953,P<0.05).There were no significant differences in the maximum transverse diameter and maximum vertical diameter of tumors between CT with 3D reconstruction technique and MRI(P>0.05).Compared with the results of CT with 3D reconstruction technique,all of 56 patients with pituitary tumor adopted resection for pituitary tumor through nasal sphenoid approach.After surgery,2 cases occurred diabetes insipidus,and 1 case occurred intracranial infection and 1 case occurred decline in olfactory function.Conclusion:Both CT with 3D reconstruction technique and MRI have higher diagnostic value for pituitary tumors in the elderly,which can display characteristics of pituitary tumors,and have direct guidance roles for the selection of surgical methods.The diagnostic specificity of CT with 3D reconstruction technique is better.

This study was aimed at investigating the infection status of orf virus(ORFV)and the genetic evolution characteristics of epidemic ORFV isolates from Anhui province.A total of 303 clinical samples collected from major meat sheep breeding cities in An-hui during 2021-2023 were subjected to ORFV detection with fluorescence quantitative PCR(qPCR).The full-length B2L and F1L genes of ORFV in the positive samples were amplified through conventional PCR and sequenced.Genetic evolution analysis of the B2L and F1L genes was conducted after sequencing.The qPCR results indicated a total ORFV positivity rate in the clinical samples of 48.8%(148/303).Multiple sequence comparisons indicated that the B2L genes of 56 sample isolates shared 96.7%-100.0%DNA and 97.4%-100.0%amino acid sequence identity.Moreover,the F2L genes of 56 sample isolates shared 95.1%-100.0%DNA and 95.0%-100.0%amino acid sequence identity.The genetic evolution tree constructed with the B2L gene DNA sequences indicated sample iso-lates and 21 reference strains located in subgroup 1,and 26 sheep-derived sample isolates and 17 reference strains located in sub-group 2.Among them,the goat-derived sample isolate FY-TYA was located in the same sub-branch as the human-derived reference strain Gansu,whereas the goat-derived sample isolate FY-XQC was located in the same sub-branch as the reference strains China Vaccine and OV-HLJ-04.The genetic evolution tree constructed with the F1L gene DNA sequences showed,the goat sample isolates FY-XQA and FY-XQC were located in the same sub-branch as the sheep-derived reference strain Xinjiang.ORFV infection was rela-tively widespread in the major meat sheep breeding areas of Anhui province,and the DNA and amino acid sequences of the B2L and F1L genes of current circulating ORFV isolates showed different degrees of genetic variation,among which F1L gene had a high de-gree of variation.Furthermore,some goat-derived sample isolates were closely related to human,vaccine,and sheep-derived refer-ence strains.These results may serve as a reference for the prevention and control of ORFV infection in Anhui province.

This paper conducts a pooled analysis of information related to orphan drugs approved for marketing in 2024 by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan. It systematically sorts out the scope of indications, therapeutic area distribution, and special review and approval pathways of these drugs, as well as their research and development progress and marketing status in China, thus providing a reference for researchers, regulatory authorities, and industry stakeholders in the field of rare disease drugs.

Objective:To construct a framework for evaluating the quality of health economic evaluation methodology based on the pragmatic clinical trial.Methods:An evaluation framework was constructed based on existing quality evaluation tools for health economic evaluation other quality evaluation tools.The weights of each item in the framework were determined by the Delphi method,and the weighted average was calculated using the expert authority coefficient.Results:A total of 23 experts were consulted,and the expert authority coefficients were 0.88 and 0.90,respectively.The results of the Wilcoxon signed-rank test showed no statistically signifi-cant differences among the expert opinions in two rounds(P＞0.05).Finally,a framework with 3 dimensions and 8 items was estab-lished.Conclusion:The evaluation framework has high scientificity and reliability.

Prescription sequence symmetry analysis (PSSA) is one of the important methods for post-marketing pharmacovigilance based on the real-world medical prescription databases. It can be used to detect prescription cascades and mine adverse drug reaction (ADR) signals, which has been verified by many studies. PSSA shows high specificity and medium sensitivity in identifying ADR. It can quantify the correlation or risks of ADR. It is easy to use and simple in algorithm, and it has good robustness to some non time-dependent confounding factors. However, the results may be affected by some human confounding factors and data quality. This paper reviews the principle, calculation method, application scope, and precaution of PSSA by reviewing related literature on PSSA domestically and abroad, in order to provide reference for pharmacovigilance in China.

Objective:To understand the application situation and role of prescription sequence symmetry analysis (PSSA) in pharmacovigilance.Methods:The relevant databases at home and abroad were searched (up to April 30, 2024), and the original articles using PSSA as the research method were collected. The basic information of the literature (first author, publication year, country, etc.), the purpose and main content of the study, the index drugs as well as the marker drugs or medical diagnoses involved in the adverse drug reactions (ADRs) were extracted. Descriptive statistical analysis was carried out.Results:A total of 66 articles were included in the analysis. The first article was published in 1996, the number of articles published in recent years has increased significantly, and those published after 2016 accounted for 68.2% (45/66). The top 3 countries in terms of published literature quantity were the United States, Denmark, and Japan. The index drugs most commonly studied were those for the cardiovascular system and the neuropsychiatric system, in 18 and 14 articles respectively. The drugs studied in 3 or more papers were hypolipidemic drugs, antihypertensive drugs, antipsychotics, antiepileptics, proton pump inhibitors, hypoglycemic drugs and anticoagulants. The targeted ADRs/diseases most studied were those about the neuropsychiatric system (in 13 studies), followed by those about the endocrine and metabolic system (in 12 studies). The research objective in 47 articles was to explore the association between index drugs and ADRs/diseases through PSSA. Finally, the associations between 21 ADRs and index drugs were identified in 24 articles, of which 9 were new ADRs not recorded in drug instructions; benefits or potential preventive and therapeutic effects of index drugs on certain diseases were found in 7 studies. Ten studies were conducted to explore ADR information of specific drugs or detect suspicious drugs that cause specific ADRs, and some correlation signals between drugs and ADRs that previously unknown were detected. Nine studies evaluated the prescribing cascades, including the use of antitussive drugs after ACEI, the prescribing cascades related to drug-induced lower urinary tract symptoms and edema, the prescription cascades of statins, and the prescribing cascade relic.Conclusion:PSSA is a useful method for identifying potential prescribing cascades and mining ADR signals using medical prescription databases, especially suitable for the safety monitoring of long-term medication for chronic diseases and the signal detection of ADR that causal relationships are difficult to determine.