Hemorrhoids are common anorectal diseases with complex pathogenesis, and there is still a lack of ideal experimental animal models for research on their prevention and treatment. In this paper, Chinese and English databases are searched with the keywords "hemorrhoids" and "animal model", and 36 relevant studies are finally included. The shortcomings of existing hemorrhoid animal models in integrating the clinical disease and syndrome characteristics of traditional Chinese and Western medicine are systematically analyzed, and the consistency of various models with clinical practice is evaluated. The studies are divided into four categories according to modeling methods: chemical modeling, physical modeling, biological modeling, and combined modeling. The clinical consistency of modeling is evaluated in combination with the diagnostic points of hemorrhoids in traditional Chinese and Western medicine. The results show that there are significant differences in the reproduction of clinical indicators by different modeling methods. According to clinical consistency, the models can be divided into three grades: high-consistency models are mainly based on combined modeling methods (such as induction by carrageenan combined with norepinephrine hydrochloride), which can more comprehensively simulate core pathological changes such as venous congestion and local inflammation; moderate-consistency models adopt single chemical or physical intervention (such as local inflammation induced by croton oil or vein ligation), which can only reproduce part of the pathological process; low-consistency models mostly adopt direct stimulation, with limited research value for pathological characteristics. Existing animal models have obvious advantages in replicating Western medical structural lesions of hemorrhoids, but they still have obvious defects in simulating the chronic disease course and stably reproducing the characteristics of traditional Chinese medicine syndromes, and a unified standard has not yet been formed for the traditional Chinese medicine evaluation system of models. In conclusion, it is still necessary to further explore the construction of high-quality integrated disease and syndrome animal models for hemorrhoids in traditional Chinese and Western medicine. Future research should integrate the theories of traditional Chinese and Western medicine, adopt multi-factor chronic modeling strategies, and establish a standardized comprehensive evaluation system covering macroscopic signs and microscopic indicators. This paper provides a reference for constructing standardized integrated disease and syndrome animal models of hemorrhoids that conform to the pathological changes of Western medicine and take into account the characteristics of traditional Chinese medicine syndromes, with the aim of providing more effective experimental tools for research on the pathogenesis of hemorrhoids and their integrated prevention and treatment with traditional Chinese and Western medicine.

Objective To explore the clinical characteristics of patients with diffuse large B-cell lymphoma (DLBCL) accompanied with KMT2D gene mutation and the impact of its co-mutated genes on prognosis. Methods Clinical data of 155 newly diagnosed DLBCL patients were obtained. The second-generation sequencing method was used to detect 475 hotspot genes, including KMT2D mutation. Patients were divided into the KMT2D mutation group and KMT2D wild-type group based on the presence or absence of KMT2D gene mutation. Clinical characteristics, differences in co-mutated genes, and survival differences between the two groups were compared. Results The frequency of KMT2D mutation was 31%, which is predominantly observed in elderly patients (P=0.07) and less in the double-expressor phenotype (P=0.07). Compared with the KMT2D wild-type group, KMT2D gene mutation was associated with higher co-mutation rates of CDKN2A (OR=2.82, P=0.01) and BCL2 (OR=3.84, P=0.016), while being mutually exclusive with MYC gene mutation (OR=0.11, P=0.013). In univariate survival analysis, no statistically significant difference in overall survival (OS) was found between the KMT2D mutation group and the wild-type group (P=0.54). Further analysis of the prognostic significance of KMT2D with other gene mutations indicated that patients with KMT2D^mutBTG2^mut had poorer OS than those with KMT2D^wt BTG2^mut (P=0.07) and KMT2D^wt BTG2^wt (P=0.05). On the contrary, patients with KMT2D^mut CD79B^mut had better OS than those with KMT2D^mut CD79B^wt (P=0.09), with no prognostic impact observed for other co-mutated genes. Multivariate Cox regression analysis revealed that Ann Arbor stages Ⅲ and Ⅳ (HR=2.751, 95%CI: 1.169-6.472, P=0.02), elevated LDH levels (HR=2.461, 95%CI: 1.396-4.337, P=0.002), Ki-67 index>80% (HR=1.875, 95%CI: 1.066-3.299, P=0.029), and KMT2D^mutBTG2^mut(HR=4.566, 95%CI: 1.348-15.471, P=0.015) were independent risk factors for OS in patients with DLBCL (P<0.05). Conclusion DLBCL patients with KMT2D mutation often have multiple gene mutations, among which patients with a co-mutated BTG2 gene have poor prognosis.

ObjectiveStudies have shown that nuciferine has anti-cerebral ischemia effect， but the specific mechanism of action has not been elaborated. Based on the transcriptome results， the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue， cell， pathological process， biological process and signaling pathway. MethodsThirty SD rats were randomly divided into the sham group， model group and nuciferine group（40 mg·kg^-1） according to weight. Except for the sham group， the model of middle cerebral artery occlusion（MCAO） was established by thread embolization method after 30 min of administration in the other two groups. Twenty-four hours after surgery， transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue， and gene ontology（GO） and kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis were performed for differentially expressed genes. The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue， cell， pathological process， biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform（TMNP）. ResultsTranscriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine. Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response， ion transport， cell proliferation and differentiation， and synaptic function. TMNP research found that at the tissue level， nuciferine could significantly improve the cerebral tissue injury caused by ischemia. At the cellular and pathological levels， nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells， mobilizing immune cells， regulating inflammation. And at the level of biological processes and signaling pathways， nuciferine mainly acted on the processes such as vascular remodeling， inflammation-related signaling pathways， and synaptic signaling. ConclusionCombined with the results of transcriptome sequencing， gene quantitative analysis and TMNP， the mechanism of nuciferine against cerebral ischemia may be related to processes such as intervening in stress response and inflammation， affecting vascular remodeling and regulating synaptic function. These results can provide a basis and reference for further study of the pharmacological mechanism of nuciferine against cerebral ischemia.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Objective:To explore the clinical value of plasma von Willebrand factor antigen(VWF:Ag)and VWF activity(VWF:GPIbM)based on ABO blood group in the risk assessment of deep vein thrombosis(DVT).Methods:A total of 163 patients with DVT who sought medical treatment from March 2021 to December 2022 were selected as the case group,and 135 healthy volunteers during the same period were selected as the control group.The differences of ABO blood groups,plasma VWF:Ag and VWF:GPIbM levels between the two groups were compared.Receiver operating characteristic(ROC)curves were used to evaluate the clinical value of VWF testing in predicting DVT events.Logistic regression analysis was applied to identify risk factors for DVT.Results:The levels of plasma VWF:Ag and VWF:GPIbM in the DVT group were significantly higher than those in the control group both overall and across ABO blood type subgroups(P＜0.01).Within the DVT group,the levels of plasma VWF:Ag and VWF:GPIbM in patients with non-O blood type were significantly higher than those with blood type O[VWF:Ag:219.74％±63.64％vs 162.21％±56.03％,P＜0.01;VWF:GPIbM:228.10％(185.15％,249.10％)vs 148.25％(116.48％,225.48％),P＜0.01].The area under the ROC curve(AUC)of VWF:Ag for predicting DVT events was 0.855,with a cut-off value of 142.4％,sensitivity of 82.2％and specificity of 72.6％;the AUC of VWF:GPIbM was 0.861,with a cut-off value of 141.2％,sensitivity of 84.7％,and specificity of 71.1％.Univariate analysis showed that both VWF:Ag and VWF:GPIbM were influencing factors for DVT events(P＜0.05).Multivariate logistic regression analysis indicated that VWF:Ag＞142.4％(OR=13.961,95％CI:7.654-25.464,P＜0.01)and VWF:GPIbM＞141.2％(OR=17.615,95％CI:9.155-33.892,P＜0.01)were independent risk factors for DVT events.Conclusion:Levels of VWF:Ag and VWF:GPIbM are significantly elevated in non-O blood type DVT patients.VWF:Ag＞142.4％and VWF:GPIbM＞141.2％are independent risk factors for DVT events.VWF testing based on ABO blood group aids in the precision prevention and control of DVT.

BACKGROUND:Mongolian medicine Echinops sphaerocephalus L.is a commonly used medicine for bone injury in Mongolian medicine.It is effective for tendon injury,fracture,bone nonunion,bone fever,tingling,sore and other diseases.Our previous studies have confirmed that Mongolian medicine Echinops sphaerocephalus L.can promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells,but its effect on angiogenesis in the process of bone defect repair is unknown.OBJECTIVE:To investigate the effect of Echinops sphaerocephalus L.on in vitro angiogenesis in human umbilical vein vascular endothelial cells and to explore the angiogenesis-promoting active ingredients and their mechanisms of action of Echinops sphaerocephalus L.using network pharmacology technology.METHODS:The ethanol extract of Echinops sphaerocephalus L.was prepared and preserved by freeze-drying.The proliferation,migration,chemotaxis and angiogenesis of human umbilical vein endothelial cells were observed after treatment with different concentrations(1 000,100,and 10 μg/mL)of Echinops sphaerocephalus L.The active components and possible signaling pathways that promoted angiogenesis were enriched and analyzed by network pharmacology.RESULTS AND CONCLUSION:(1)The effect of Echinops sphaerocephalus L.on angiogenesis was regulated by its mass concentration:at low mass concentration(10 μg/mL),Echinops sphaerocephalus L.could promote the proliferation,migration,chemotaxis and angiogenesis of human umbilical vein vascular endothelial cells;on the contrary,Echinops sphaerocephalus L.inhibited the proliferation,migration,and chemotaxis of human umbilical vein endothelial cells at high mass concentration(1 000 μg/mL).However,the inhibitory effect of Echinops sphaerocephalus L.on angiogenesis was not significant at high mass concentration due to the limitation of experimental time.10 μg/mL Echinops sphaerocephalus L.could up-regulate the mRNA expression of angiogenesis-associated factors,including kinase insert domain receptor,vascular endothelial growth factor A,and hypoxia-inducible factor α,and thereby influenced angiogenesis during bone repair.(2)Network pharmacological analyses indicated that Echinops sphaerocephalus L.may bind to eight core targets(TGFB1,TNF,IL-6,STAT3,CTNNB1,IL-1B,AKT1,and HIF-1A)through four core active components(apigenin,caffeic acid,quercetin,and chlorogenic acid)to exert an effect on angiogenesis,atherosclerosis,multiple viral infections,and tumor angiogenesis-related signaling pathways.

Objective:To explore the predictive value of serum Dickkopf-related protein 1 (DKK1) and chemokine 21 (CCL21) expression for the pulmonary fibrosis progression in patients with rheumatoid arthritis associated interstitial lung disease (RA-ILD).Methods:A prospective study method was used. One hundred and eight patients with RA-ILD (RA-ILD group) and 108 patients with simple rheumatoid arthritis (RA group) from September 2020 to July 2023 in Jincheng People's Hospital were selected. The patients with RA-ILD were treated with disease-modifying antirheumatic drugs and anti fibrotic drugs. Before treatment, the serum DKK1, CCL21, C-reactive protein (CRP), anti cyclic citrullinated peptide antibody (ACPA), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) salivary liquefied glycan antigen 6 (KL-6) were detected; the 28 joints disease activity score (DAS28) and Warrick score were assessed. The patients with RA-ILD were followed up for 1 year, and the occurrence of pulmonary fibrosis progression was recorded. The patients with pulmonary fibrosis progression were included in the progressive subgroup and vice versa in the stable subgroup. Multivariate Logistic regression was used to analyze the independent risk factors for predicting pulmonary fibrosis progression within 1 year in patients with RA-ILD. The predictive value of serum DKK1 and CCL21 for predicting the pulmonary fibrosis progression within 1 year in patients with RA-ILD was analyzed by receiver operating characteristic (ROC) curve. The decision curve of serum DKK1 and CCL21 to predict the pulmonary fibrosis progression within 1 year in patients with RA-ILD was plotted using the R language package.Results:The DKK1 in RA-ILD group was significantly lower than that in RA group: (76.02 ± 9.80) ng/L vs. (86.44 ± 9.26) ng/L, the CCL21 was significantly higher than that in RA group: (202.02 ± 25.86) ng/L vs. (172.42 ± 18.35) ng/L, and there were statistical differences ( P<0.01). The patients with RA-ILD were followed up for 1 year, 25 cases (23.15%) developed pulmonary fibrosis progression (progressive subgroup), and 83 cases did not develop pulmonary fibrosis progression (stable subgroup). The Warrick score, CCL21, ACPA and KL-6 in progressive subgroup were significantly higher than those in stable subgroup: (11.80 ± 3.56) scores vs. (7.75 ± 1.81) scores, (224.53 ± 27.26) ng/L vs. (195.25 ± 21.32) ng/L, (452.46 ± 38.35) kU/L vs. (414.37 ± 31.63) kU/L and (466.35 ± 42.32) kU/L vs. (416.82 ± 38.34) kU/L, the DKK1 was significantly lower than that in stable subgroup: (68.65 ± 8.24) ng/L vs. (78.24 ± 9.15) ng/L, and there were statistical differences ( P<0.01); there were no statistical differences in DAS28, RF, ERS and CRP between the two subgroups ( P>0.05). Multivariate Logistic regression analysis result showed that Warrick score, DKK1, CCL21, ACPA and KL-6 were independent risk factors for predicting pulmonary fibrosis progression within 1 year in patients with RA-ILD ( OR = 2.601, 0.752, 1.110, 1.062 and 1.038; 95% CI 1.227 to 5.517, 0.578 to 0.978, 1.019 to 1.209, 1.009 to 1.118 and 1.001 to 1.076; P<0.05). The ROC curve analysis result showed that the area under the curve of DKK1 and CCL21 for predicting pulmonary fibrosis progression within 1 year in patients with RA-ILD was 0.779 and 0.795, with optimal cutoff values of 74.750 and 207.615 ng/L. The area under the curve of DKK1 combined with CCL21 for predicting pulmonary fibrosis progression within 1 year in patients with RA-ILD was 0.873. The decision curve analysis result showed that the DKK1 combined with CCL21 for predicting pulmonary fibrosis progression within 1 year could improve the predictive value (the maximum benefit rate was 23.15%). Conclusions:Compared with RA patients, RA-ILD patients have decreased serum DKK1 levels and increased CCL21 levels. In patients with RA-ILD, the low expression of DKK1 and high expression of CCL21 are the risk factors of pulmonary fibrosis progression, and detecting serum levels of DKK1 and CCL21 can predict the risk of pulmonary fibrosis progression.

Objective To quantitatively assess the correlation between the skeletal muscle index(SMI)of patients and the occur-rence of anastomotic leakage(AL)in rectal cancer patients after surgery,and to analyze the risk factors for AL in rectal cancer patients and the influencing factors of sarcopenia.Methods The clinical,pathological,and related imaging data of 362 patients who under-went radical surgery for rectal cancer were retrospectively analyzed.All patients underwent pelvic MRI and abdominal CT scans(plain/enhanced)within one month before surgery,and the third lumbar vertebra skeletal muscle area(L3-SMA)was measured from the images.All patients were divided into AL group(56 cases)and control group(306 cases)based on the presence or absence of postoperative complications.The differences in clinical characteristics and imaging parameters between the two groups were analyzed.A logistic risk prediction model was established.Results Significant differences were observed between the two groups in sarcopenia,type of surgery,surgical approach,serum albumin level,operation duration,stoma type,and extramural vascular invasion(EMVI)(P＜0.05).These factors were incorporated in a multivariate logistic regression analysis model,the area under the curve(AUC)of receiver operating characteristic(ROC)curve of the model was 0.810[95％confidence interval(CI)0.743-0.876,P＜0.001],with a sensitivity of 0.865 and specificity of 0.669.Conclusion Sar-copenia is a significant risk factor for AL after rectal cancer surgery.It enhances the predictive efficacy for postoperative AL and serves as a basis for identifying high-risk populations for AL in clinical practice.

Chronic kidney disease (CKD) is a significant global public health issue. In recent years, several new drugs have shown substantial efficacy in CKD treatment. Sodium-glucose cotransporter 2 inhibitors, nonsteroidal mineralocorticoid receptor antagonists, and glucagon-like peptide-1 receptor agonists improve renal outcomes in CKD patients through various mechanisms, and also demonstrate favorable effects on cardiovascular outcomes. Novel agents, including endothelin receptor antagonists, are accumulating clinical evidence for delaying kidney disease progression, with ongoing development of new therapeutic targets. This article reviewed the latest research progress of these drugs in CKD treatment, offering new perspectives and reference points for comprehensive CKD management.