Objective To explore the inhibitory effect of guggulsterone(GS)on diethylnitrosamine(DEN)-induced liver fibrosis in rats and its mechanism.Methods DEN-induced liver fibrosis model was established in SD rats.The successful model rats were randomly divided into model group(n=6),GS group(n=6,50 mg/kg,intraperitoneal injection for 4 weeks),GS+SRI group(n=6,50 mg/kg+30 mg/kg,intraperitoneal injection for 4 weeks),and control group(n=6,without DEN-induced).Rats in the control group and the model group were injected with the same amount of normal saline.The pathological changes of the liver were detected by HE staining.Serum liver function indexes including alanine aminotransferase(ALT),aspartate aminotransferase(AST),albumin(ALB)and alkaline phosphatase(ALP)were detected by automatic biochemical analyzer.The serum levels of pro-collagen Ⅲ(PC-Ⅲ),collagen Ⅳ(Ⅳ-C),hyaluronidase(HA),laminin(LN),malondialdehyde(MDA),reduced glutathione(GSH),superoxide dismutase(SOD),and catalase(CAT)were detected by ELISA assay.The mRNA and protein expression of TGF-β1,Smad2,and p-Smad3/Smad3 were detected by Real-time PCR and Western blotting.Results Compared with the control group,the model group showed typical pathological changes of liver fibrosis;the serum ALB,GSH,SOD and CAT levels were significantly decreased(P＜0.05);the serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA,LN and the mRNA expression of TGF-β1,Smad3 and protein expression of TGF-β1,p-Smad3 in liver tissues were significantly increased(P＜0.05).Compared with the model group,the pathological changes of liver fibrosis in the GS group were alleviated,and the serum levels of ALB,GSH,SOD and CAT were significantly increased(P＜0.05),the serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA and LN,the mRNA expression of TGF-β1 and Smad3,and protein expression of TGF-β1 and p-Smad3 in liver tissues were significantly decreased(P＜0.05).In addition,after the administration of SRI,TGF-β1 signaling pathway activator,compared with the GS group,the GS+SRI group showed significantly decreased serum ALB,GSH,SOD and CAT levels(P＜0.05),but significantly increased serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA and LN as well as the mRNA expression of TGF-β1 and Smad3 and protein expression of TGF-β1 and p-Smad3 in liver tissues(P＜0.05).Therefore,SRI attenuated the anti-fibrotic effect of GS on rats with liver fibrosis.Conclusion GS has certain inhibitory effect on DEN-induced liver fibrosis in rats,and its mechanism may be related to the reduction of oxidative stress level and the inhibition of the activation of TGF-β1/Smad3 signaling pathway.

Cancer is a serious global health problem and a major cause of human death. Conventional cancer treatments often run the risk of impairing vital organ functions. Anticancer peptides (ACPs) are considered to be one of the most promising therapeutic agents against common human cancers due to their small sizes, high specificity, and low toxicity. Since ACP recognition is highly limited to the laboratory, expensive, and time-consuming, we proposed pLM4ACP, a model for predicting ACPs based on machine learning and protein language models. In this model, the protein language model ProtT5 was used to extract the features of ACPs, and the extracted features were input into the support vector machine (SVM) classification algorithm for optimization and performance evaluation. The model showcased significantly higher accuracy than other methods, with the overall accuracy of 0.763, F1-score of 0.767, Matthews correlation coefficient of 0.527, and area under the curve of 0.827 on the independent test set. This study constructs an efficient anticancer peptide prediction model based on protein language models, further advancing the application of artificial intelligence in the biomedical field and promoting the development of precision medicine and computational biology.
Machine Learning ; Antineoplastic Agents/chemistry* ; Humans ; Peptides/chemistry* ; Support Vector Machine ; Algorithms ; Computational Biology/methods* ; Neoplasms/drug therapy*

Objective:To investigate associations of plasma D-dimer and fasting blood glucose with the outcome in patients with acute ischemic stroke (AIS).Methods:Patients with AIS admitted to the Department of Neurology, Dagang Hospital, Binhai New Area, Tianjin from January 2018 to December 2023 were included retrospectively. The demographic characteristics, baseline clinical data, and laboratory findings were collected. According to the modified Rankin Scale score at 3 months after onset, the patients were divided into a good outcome group (0-2) and a poor outcome group (>2). Multivariate logistic regression analysis was used to determine the independent related factors for the outcome in patients with AIS. Results:A total of 1 967 patients were enrolled, including 1 287 males(65.4%), aged 67.80±11.58 years. The median baseline National Institutes of Health Stroke Scale (NIHSS) score was 4 (interquartile range, 2-7). One thousand five hundred and twenty-three patients (77.4%) had good outcome, and 444 (22.6%) had poor outcome. Univariate analysis showed that age, baseline systolic blood pressure, baseline NIHSS score, fasting blood glucose and D-dimer, as well as the proportion of patients with a history of ischemic heart disease, previous stroke or transient ischemic attack in the poor outcome group were significantly higher than those in the good outcome group (all P<0.05). Multivariate logistic regression analysis showed that older age (odds ratio [ OR] 1.286, 95% confidence interval [ CI] 1.137-1.458; P=0.037), complicated with ischemic heart disease ( OR 1.598, 95% CI 1.024-2.227; P=0.046), higher baseline systolic blood pressure ( OR 1.011, 95% CI 1.002-1.045; P=0.037), higher baseline NIHSS score ( OR 1.432, 95% CI 1.132-1.587; P<0.001), higher baseline D-dimer ( OR 4.001, 95% CI 1.839-8.703; P=0.040), and higher fasting blood glucose ( OR 1.175, 95% CI 1.078-1.282; P=0.045) were independently associated with the poor outcome. Conclusion:Higher D-dimer and fasting blood glucose are associated with the poor outcome in patients with AIS.

Objective To explore the inhibitory effect of guggulsterone(GS)on diethylnitrosamine(DEN)-induced liver fibrosis in rats and its mechanism.Methods DEN-induced liver fibrosis model was established in SD rats.The successful model rats were randomly divided into model group(n=6),GS group(n=6,50 mg/kg,intraperitoneal injection for 4 weeks),GS+SRI group(n=6,50 mg/kg+30 mg/kg,intraperitoneal injection for 4 weeks),and control group(n=6,without DEN-induced).Rats in the control group and the model group were injected with the same amount of normal saline.The pathological changes of the liver were detected by HE staining.Serum liver function indexes including alanine aminotransferase(ALT),aspartate aminotransferase(AST),albumin(ALB)and alkaline phosphatase(ALP)were detected by automatic biochemical analyzer.The serum levels of pro-collagen Ⅲ(PC-Ⅲ),collagen Ⅳ(Ⅳ-C),hyaluronidase(HA),laminin(LN),malondialdehyde(MDA),reduced glutathione(GSH),superoxide dismutase(SOD),and catalase(CAT)were detected by ELISA assay.The mRNA and protein expression of TGF-β1,Smad2,and p-Smad3/Smad3 were detected by Real-time PCR and Western blotting.Results Compared with the control group,the model group showed typical pathological changes of liver fibrosis;the serum ALB,GSH,SOD and CAT levels were significantly decreased(P＜0.05);the serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA,LN and the mRNA expression of TGF-β1,Smad3 and protein expression of TGF-β1,p-Smad3 in liver tissues were significantly increased(P＜0.05).Compared with the model group,the pathological changes of liver fibrosis in the GS group were alleviated,and the serum levels of ALB,GSH,SOD and CAT were significantly increased(P＜0.05),the serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA and LN,the mRNA expression of TGF-β1 and Smad3,and protein expression of TGF-β1 and p-Smad3 in liver tissues were significantly decreased(P＜0.05).In addition,after the administration of SRI,TGF-β1 signaling pathway activator,compared with the GS group,the GS+SRI group showed significantly decreased serum ALB,GSH,SOD and CAT levels(P＜0.05),but significantly increased serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA and LN as well as the mRNA expression of TGF-β1 and Smad3 and protein expression of TGF-β1 and p-Smad3 in liver tissues(P＜0.05).Therefore,SRI attenuated the anti-fibrotic effect of GS on rats with liver fibrosis.Conclusion GS has certain inhibitory effect on DEN-induced liver fibrosis in rats,and its mechanism may be related to the reduction of oxidative stress level and the inhibition of the activation of TGF-β1/Smad3 signaling pathway.

OBJECTIVE To study the correlation between SLCO1B1 （521T＞C and 388A＞G） gene polymorphisms and the efficacy and safety of rosuvastatin. METHODS Retrieved from PubMed， Embase， Cochrane Library， PharmGKB， CNKI database and Wanfang database， the studies about the effects of 521T＞C and 388A＞G gene polymorphisms on the efficacy and safety of rosuvastatin were collected during the inception to Dec. 2023. The included data were analyzed by using RevMan 5.3 software. RESULTS A total of 16 studies were included. The results of meta-analysis showed that 521T＞C gene polymorphism was significantly correlated with the efficacy of rosuvastatin. In the dominant gene model， compared with TT genotype， CC+TC genotype significantly improved the efficacy of rosuvastatin in raising high-density lipoprotein cholesterol （HDL-C） [MD＝2.38， 95%CI（0.61，4.16）， P＝0.009 0]. In the homozygous gene model， compared with TT genotype， CC genotype significantly improved the efficacy of rosuvastatin in reducing total cholesterol [MD＝－7.50，95%CI（－13.05， －1.95）， P＝0.008 0]. In heterozygous gene model， compared with TT genotype， TC genotype significantly improved rosuvastatin in reducing low-density lipoprotein cholesterol （LDL-C） [MD＝－5.14， 95%CI（－9.74， －0.53）， P＝0.03] and increasing HDL-C [MD＝5.67， 95%CI 232102311200） （2.61， 8.73）， P＝0.000 3]. 388A＞G gene polymorphism was also significantly correlated with the efficacy of rosuvastatin. In dominant or homozygous gene models， compared with AA E-mail：dushuzhang911@163.com genotype， GG+AG genotype [MD＝－6.88， 95%CI （－7.46，－6.30），P＜0.000 1] or GG genotype [MD＝－9.23， 95%CI（－9.41， 9.04）， P＜0.000 1] significantly improved the efficacy of rosuvastatin in lowering LDL-C. In the heterozygous gene model， compared with AA genotype， AG genotype significantly improved the efficacy of rosuvastatin in lowering LDL-C [MD＝－3.00， 95%CI（－3.19， －2.82）， P＜0.000 1]， total cholesterol [MD＝－5.80， 95%CI（－6.00， －5.59）， P＜0.000 1] and triglyceride [MD＝－11.79， 95%CI（－19.57， －4.02）， P＝0.003 0]. In the recessive gene model， compared with AA+AG genotype， GG genotype significantly improved the therapeutic efficacy of rosuvastatin in reducing LDL-C[MD＝－4.31， 95%CI（－8.47， －0.14）， P＝0.040 0] and elevating HDL-C [MD＝4.49， 95%CI （2.20， 6.77）， P＝0.000 1]. Under 4 gene models， there was a significant correlation between 521T＞C gene polymorphism and rosuvastatin-related ADR probability （P＜0.05）， but no significant correlation was found in 388A＞G gene polymorphism （P＞0.05）. CONCLUSIONS The polymorphism of 521T＞C gene is significantly related to the efficacy and safety of rosuvastatin in lowering lipid， and the C allele may be one of the factors leading to the increase of rosuvastatin in lipid-lowering efficacy and ADR. 388A＞ G gene polymorphism is significantly associated with the lipid-lowering efficacy of rosuvastatin， but not with its safety.

Objective: To investigate the marriage intention and its influencing factors among HIV-infected men who have sex with men (MSM), so as to provide the reference for formulating high-risk behavior intervention strategies and reducing the risk of HIV transmission among this population. Methods: Unmarried HIV-infected MSM were sampled from newly reported HIV/AIDS patients in Gongshu District of Hangzhou City from 2020 to 2022. Participants' sociodemographic information, family status and marriage intention were collected using questionnaire surveys. Factors affecting marriage intention were identified using a multivariable logistic regression model. Results: A total of 430 questionnaires were allocated and 400 valid questionnaires were recovered, with an effective recovery rate of 93.02%. The respondents had a mean age of (28.90±4.67) years, and included 271 cases with registered residence outside Hangzhou City (67.75%). There were 82 cases indicating that they would probably or definitely get married, accounting for 20.50%, including 46 cases (56.10%) aged 30 years and older, 67 cases (81.71%) engaged in commercial services/freelance work/worker and 53 cases (64.63%) being the only children. Multivariable logistic regression analysis showed that unmarried HIV-infected MSM who were aged 30 years and older (OR=2.751, 95%CI: 1.230-6.154), had a monthly income of <10 000 Yuan (5 000 to <10 000 Yuan, OR=7.010, 95%CI: 2.049-23.981; <5 000 Yuan, OR=5.229, 95%CI: 1.803-15.165), had a high school education and below (OR=5.935, 95%CI: 1.775-19.844), were the only children (OR=3.407, 95%CI: 1.468-7.910), came from families with economic conditions above the average level (OR=8.906, 95%CI: 2.070-38.308), did not disclose their sexual orientation (OR=3.298, 95%CI: 1.118-9.727), held a positive attitude towards government policies (OR=70.544, 95%CI: 14.583-341.237), had no homosexual intercourse in the past six months (OR=3.583, 95%CI: 1.278-10.044), and had not informed their sexual partners of their HIV status (OR=2.910, 95%CI: 1.228-6.897) were more willing to get married. Conclusion A certain proportion of unmarried HIV-infected MSM in Gongshu District are willing to get married, and their marriage intention is affected by age, educational level, family economic conditions, the only children or not, disclosing sexual orientation or not, having homosexual intercourse in the past six months or not, informing sexual partners of HIV status or not, and the attitude towards government policies.

Objective:To investigate the association of serum uric acid (SUA) with the outcome in patients with acute ischemic stroke (AIS) at one year after onset.Methods:Patients with AIS admitted to the Department of Neurology, Dagang Hospital, Tianjin Binhai New Area were included retrospectively. According to the modified Rankin Scale (mRS) score at 1 year after onset, patients were divided into a good outcome group (0-2) and a poor outcome group (>2). They were also divided into a survival group and a death group based on their survival status at 1 year after onset. The clinical baseline data and laboratory tests were compared. Multivariate logistic regression analysis was used to determine the associations of SUA with poor outcome and death in patients with AIS. Results:A total of 651 patients were enrolled, including 430 males (66.1%) aged 67.5±11.7 years. Four hundred and fourteen patients (63.6%) were in the good outcome group, and 237 (36.4%) were in the poor outcome group. There were 568 patients (87.3%) in the survival group and 43 (16.7%) in the death group. Univariate analysis showed that there were differences in age, atrial fibrillation, history of stroke or transient ischemic attack, baseline National Institutes of Health Stroke Scale (NIHSS) score, and pre-admission mRS score between the poor outcome group and the good outcome group. The homocysteine, SUA, white blood cell count, and creatinine in the poor outcome group were higher than those in the good outcome group, while the red blood cell count and hemoglobin were lower than those in the good outcome group (all P<0.05). There were differences in age, history of ischemic heart disease, atrial fibrillation, history of stroke or transient ischemic attack, baseline NIHSS score, pre-admission mRS score, and stroke etiology classification between the survival group and the death group. Hemoglobin and triglycerides in the survival group were higher than those in the death group, while the white blood cell count and creatinine were lower than those in the death group (all P<0.05). Multivariate logistic regression analysis showed that SUA was an independent risk factor for poor outcome in patients with AIS (odds ratio 1.004, 95% confidence interval 1.001-1.006; P<0.01), but there was no independent correlation with death. Conclusion:Higher SUA is an independent risk factor for poor outcome at one year after onset in patients with AIS.

Objective:To explore the role of arginine metabolism in the inflammatory response to influenza A virus (FluA) infection.Methods:Eighteen-month-old mice were infected with FluA via nasal drip, with samples collected on the 6th day post-infection. The concentration of cytokines was determined by the Luminex multifactor assay, while the metabolites in bronchoalveolar lavage fluid (BALF) were analyzed using targeted metabolomic method. Correlation analysis was employed to examine the correlation between cytokines and metabolites. Macrophages were infected with FluA at a multiplicity of infection (MOI) of 1 and cultured with different concentrations of arginine for 24 h. The mRNA and protein expression levels of interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α) and IL-10 were detected by real time fluorescence quantitative RT-PCR (qRT-PCR) and Cytometric Bead Array (CBA).Results:In comparison to the control group, the levels of surfactant protein D (SP-D), TNF-α, monocyte chemotactic protein-1 (MCP-1), IL-1α, IL-6, IL-10, recombinant S100 calcium binding protein (S100) A9, interferon inducible protein 10 (IP-10), macrophage inflammatory protein-1α (MIP-1α), matrix metalloprotein-9 (MMP-9), and Complement Factor D in BALF of FluA infection exhibited a significant elevation. The concentrations of arginine, aspartate, citrulline, glutamic acid, ornithine, proline, creatine, and sarcosine in arginine metabolism were up-regulated, which was correlated with most of elevated cytokine levels. The supplementation of arginine after FluA infection significantly decreased the levels of IL-1β, IL-6, and TNF-α, but increased the level of IL-10 in macrophages.Conclusions:Arginine reduces the inflammatory response induced by FluA infection in macrophages, suggesting that it may be a potential intervention target for severe pulmonary inflammation following FluA infection.

Objective:To enhance the understanding of the diagnosis and individualized treatment of myelodysplastic syndrome/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T).Methods:A retrospective case series study was conducted. The clinical data, diagnosis and treatment process and prognosis of 4 patients with MDS/MPN-RS-T admitted to Affiliated Hospital of Hebei University from September 2015 to May 2021 were retrospectively analyzed, and the related literature was reviewed.Results:All the 4 patients were male, aged 63 to 75 years. Patients 1 and 2 were classified as revised international prognostic scoring system (IPSS-R) high-risk group, combined with ASXL1 mutation and high risk cytogenetic abnormality. The therapeutic effect of various treatment regimens was poor, and they were converted to acute myeloid leukemia (AML) and then died due to disease progression. Patient 3 was classified as IPSS-R medium-risk group. His main manifestation was myelodysplastic syndrome (MDS) combined with ring sideroblasts in the early stage and was transformed into MDS/MPN-RS-T during the treatment, and JAK2 mutation occurred in the subsequent treatment. After lenalidomide treatment, the patient was removed from blood transfusion and the condition was stable at present. Patient 4 was classified as IPSS-R medium-risk group, and lenalidomide showed significant therapeutic effects and he was in stable condition.Conclusions:Lenalidomide can significantly improve transfusion dependence in patients with MDS/MPN-RS-T, and ASXL1 mutation and high-risk cytogenetic abnormality may be associated with AML transformation.

Background and objective Lung cancer is the malignant tumor with the highest incidence rate and the heaviest disease burden in China.In recent years,lung cancer has shown a high incidence trend,seriously affecting the health of the population.In this paper,we analyze the characteristics of lung cancer incidence in 2019 and the trend of incidence rate from 2010-2019 in the tumor registration area of Gansu province,in order to provide a reference basis for the development of lung cancer prevention and control strategies in Gansu province.Methods By analyzing the cases of lung cancer incidence in the tumor registration area of Gansu province in 2019,we calculated the incidence rate,medium incidence rate,world in-cidence rate and other related indexes;we used Joinpoint to calculate the annual percentage change(APC)for trend analysis.Results In 2019,a total of 3757 new cases of lung cancer were reported in Gansu province,accounting for 14.96%of all new malignant tumors.The incidence rate,medium incidence rate and world incidence rate and world rate of lung cancer were 40.52/105,25.78/105,25.86/105;and the cumulative rate of 0-74 years old,and the truncation rate of 35-64 years old were 3.23%,40.03/105,respectively.The incidence of lung cancer rises with age,and is high in the age group of 40 years and above,and the incidence peaks in the male and female populations in the group of 75 years and above,and the group of 80 years and above,respectively.The crude incidence rate of lung cancer in the tumor registration area of Gansu province from 2010-2019 showed an overall increasing trend,and the rate of increase was relatively fast,with an APC 5.39%(P<0.05);Separately,accord-ing to gender,urban and rural areas,the incidence of lung cancer in all populations showed an increasing trend,and the APC of male,female,urban and rural populations were 4.98%,6.39%,6.26%,and 4.64%,respectively(all P<0.05).According to the trend analysis of lung cancer incidence rate by age group,only lung cancer incidence in the age group of 65 years and above increased at an annual average rate of 4.15%(P<0.05).Conclusion The incidence rate of lung cancer in the tumor registration area of Gansu province from 2010 to 2019 shows a rising trend year by year,and there are differences in the incidence of lung cancer in people of different genders,regions and age groups,so comprehensive prevention and control work should be carried out for the key populations of lung cancer incidence.