Stroke, a major cerebrovascular disease, has high morbidity and mortality. Effective methods to reduce the risk and improve the prognosis are lacking. Currently, uric acid (UA) is associated with the pathological mechanism, prognosis, and therapy of stroke. UA plays pro/anti-oxidative and pro-inflammatory roles in vivo. The specific role of UA in stroke, which may have both neuroprotective and damaging effects, remains unclear. There is a U-shaped association between serum uric acid (SUA) levels and ischemic stroke (IS). UA therapy provides neuroprotection during reperfusion therapy for acute ischemic stroke (AIS). Urate-lowering therapy (ULT) plays a protective role in IS with hyperuricemia or gout. SUA levels are associated with the cerebrovascular injury mechanism, risk, and outcomes of hemorrhagic stroke. In this review, we summarize the current research on the role of UA in stroke, providing potential targets for its prediction and treatment.
Humans ; Uric Acid/metabolism* ; Stroke/drug therapy* ; Animals ; Hyperuricemia/drug therapy* ; Ischemic Stroke/blood* ; Biomarkers/blood*

Objective: To screen and identify the key active molecules, signaling pathways, and therapeutic targets of Shuxuening (SXN) injection for treating liver cirrhosis (LC) and to evaluate its therapeutic potential using a mouse model. Methods: Target genes of SXN and LC were retrieved from public databases, and enrichment analysis was performed. A protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and hub genes were identified using Molecular Complex Detection (MCODE). LC was induced in rats and mice via intraperitoneal injections of diethylnitrosamine and carbon tetrachloride (CCl4) for 12 weeks. Starting at week 7, SXN was administered intraperitoneally to the mice in the treatment group. Serum and liver tissues of the mice were collected for the detection of indicators, pathological staining, and expression analysis of hub targets using quantitative real-time polymerase chain reaction (qRT-PCR). Results: We identified 368 overlapping genes (OLGs) between SXN and LC targets. These OLGs were subsequently used to build a PPI network and to screen for hub genes. Enrichment analysis showed that these genes were associated with cancer-related pathways, including phosphoinositide-3-kinase/Akt and mitogen-activated protein kinase signaling and various cellular processes, such as responses to chemicals and metabolic regulation. In vivo experiments demonstrated that SXN treatment significantly improved liver function and pathology in CCl4-induced LC mice by reducing inflammation and collagen deposition. Furthermore, qRT-PCR demonstrated that SXN regulated the expression of MAPK8, AR and CASP3 in the livers of LC mice. Conclusion This study highlighted the therapeutic effects of SXN in alleviating LC using both bioinformatics and experimental methods. The observed effect was associated with modulation of hub gene expression, particularly MAPK8, and CASP3.

Objective To study the relationship between waist-to-height ratio(WHtR)and new-onset cerebral infarction in the elderly with hypertension.Methods A total of 9 096 elderly hypertensive patients were enrolled from the Kailuan study population.Using the first occurrence of cerebral infarction as the endpoint event,a prospective cohort study was performed.According to the WHtR value of the subjects with an interval of 0.05,the subjects were divided into G1 group(WHtR＜0.45),G2 group(0.45≤WHtR＜0.50),G3 group(0.50≤WHtR＜0.55),and G4 group(WHtR≥0.55).The cumulative incidence rate of endpoint event in each population were statistically analyzed using the life table method.Cox proportional hazards regression analysis was used to explore the role of WHtR in the occurrence of new cerebral infarction.Model 1 was a single factor Cox proportional hazards analysis model,only considering the influence of WHtR on the risk of cerebral infarction.After adjusting sex,age,body weight,serum hypersensitive C-reactive protein,systolic blood pressure,serum triglycerides,smoking history,fasting blood glucose,alcohol consumption,high-density lipoprotein cholesterol,diastolic blood pressure,exercise,low-density lipoprotein cholesterol,educational level,antihypertensive drug history,model 2 was established to observe the influence of WHtR on the occurrence of new-onset cerebral infarction.Results The follow-up lasted(9.3±2.7)years.Compared to the G2 group,multivariate Cox proportional hazards regression model showed that the hazard ratio HR(95%CI)for cerebral infarction in model 1 was 1.00(0.67～1.50),1.29(1.05～1.60)and 1.36(1.12～1.66)respectively in G1,G3 and G4;and that in model 2 was 1.09(0.72～1.65),1.24(0.99～1.54)and 1.31(1.05～1.62)respectively in G1,G3 and G4.Conclusion The risk of cerebral infarction in the elderly with hypertension is the lowest when WHtR between 0.45≤WHtR＜0.50,and WHtR greater than or equal to 0.55 is associated with an increased risk of new-onset cerebral infarction.

Objective To investigate,before and after sucrose challenge,the difference of saliva microbiome between caries-free(CF)and caries-active(CA)individuals,and to explore the potential key microorganisms that is more susceptible to sucrose chal-lenge.Methods Eighteen systemic healthy volunteers,among which 8 were caries-free and 10 were caries-active,were recruited.Sa-liva samples were collected pre-treatment and at 30 min and 2 h after the sucrose treatment.Microbial diversity and community structure were analyzed and compared using Illumina sequencing platform.Results The diversity and abundance of saliva samples from caries-free individuals was similar to that from caries-active individuals before sucrose treatment.After 2 h of treatment,the microbial diversity of the CA group was significantly higher than that of the CF group(P＜0.05).The results of Beta diversity analysis showed no signifi-cant difference between the two groups.The dominant species,which were represented as Pseudomonas,Streptococcus,Prevotella,Al-loprevotella,Neisseria and Veillonella,in the two groups were similar but different in abundance.There was no significant change in the abundance difference of Veillonella between CF and CA before and after treatment.The abundance differences of Prevotella and Allopre-votella between CF and CA increased and the abundance difference of Neisseria decreased after sucrose treatment.The results of LEfSe analysis showed that Prevotella,as one of the dominant bacteria in the two groups,was significantly more abundant in the CA group than in the CF group after sucrose treatment,suggesting its potential biomarker role.Conclusion The diversity and composition of sa-liva microbiome changes subject to sucrose challenge,which is more significant in caries-affected individuals.The response of salivary microbe to sucrose challenge is different between caries-free and caries-active individuals.Prevotella is a potential biomarker of caries.

Objective:To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis.Methods:This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924 th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results:Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m 2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions:The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.

Objective To investigate the effect of ankyrin-repeat domain-containing protein 22(ANKRD22)on the proliferation,invasion,and migration of human hepatoma cells and its molecular mechanism.Methods The TCGA database was used to analyze the expression level of ANKRD22 in normal liver tissue and hepatocellular carcinoma tissue and its association with prognosis.Western Blot and qRT-PCR were used to measure the expression of ANKRD22 in human normal liver cells(L-02)and human hepatoma cells(Huh7,HepG2,MHCC-97H,SK-HEP-1,and SMMC-7721);CCK-8 assay,EdU,wound healing assay,and Transwell assay were used to observe the effect of ANKRD22 on the proliferation,invasion,and migration of hepatoma cells;Western Blot was used to investigate the association of ANKRD22 with cyclins and EMT-related proteins;KEGG and ssGSEA analyses were performed to investigate the mechanism of action of ANKRD22 in hepatoma cells,and related experiments were conducted for validation.The independent-samples t-test was used for comparison of continuous data between two groups;a one-way analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results In the TCGA database,the expression level of ANKRD22 in hepatoma tissue was significantly higher than that in normal liver tissue(t=5.083,P<0.05),and the patients with a high expression level of ANKRD22 had longer overall survival and disease-related survival than those with a low expression level of ANKRD22(P<0.05).The expression level of ANKRD22 in various human hepatoma cell lines was higher than that in human normal liver cells(all P<0.05).Cell proliferation assay showed that the ANKRD22 overexpression group had significantly higher EdU positive rate and proliferation rate than the Vector group(t=19.60 and 6.72,both P<0.001),and compared with the si-NC group,the si-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower EdU positive rate and proliferation rate(all P<0.001).Compared with the Vector group,the overexpression group had significantly higher expression levels of Cyclin E1,Cyclin D1,CDK7,and CDK4(t=3.54,4.95,6.34,and 5.19,all P<0.01),and the si-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower expression levels than the si-NC group(all P<0.001).The overexpression group had a significantly lower expression level of P27 than the Vector group(t=6.12,P<0.001),and the si-ANKRD22#2 group and the si-ANKRD22#3 group had a significantly higher expression level than the si-NC group(both P<0.001).Invasion and migration experiments showed that compared with the Vector group,the ANKRD22 overexpression group had significantly higher migration rate and number of crossings through the membrane(migration group and invasion group)(t=5.01,25.60,and 3.67,all P<0.05),and compared with the si-NC group,thesi-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower migration rate and number of crossings through the membrane(migration group and invasion group)(all P<0.01).The overexpression group had significantly higher expression levels of N-cadherin,Vimentin,and Snail than the Vector group(t=12.13,8.85,and 13.97,all P<0.001),and the si-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower expression levels than the si-NC group(all P<0.001);the overexpression group had a significantly lower expression level of E-cadherin than the Vector group(t=4.98,P<0.01),and the si-ANKRD22#2 group and the si-ANKRD22#3 group had a significantly higher expression level than the si-NC group(both P<0.001).The KEGG enrichment analysis and the ssGSEA analysis showed that ANKRD22 was associated with the PI3K/AKT/mTOR signaling pathway in hepatocellular carcinoma,and the overexpression group had significantly higher expression levels of p-AKT/AKT,p-PI3K/PI3K,and p-mTOR/mTOR than the Vector group(t=12.21,3.43,and 9.75,all P<0.01),and the si-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower expression levels than the si-NC group(all P<0.001).Conclusion ANKRD22 is highly expressed in hepatoma cells and can promote the proliferation,invasion,and migration of hepatoma cells and the activation of the PI3K/AKT/mTOR signaling pathway.

OBJECTIVE To systematically evaluate the efficacy and safety of transcatheter arterial chemoembolization （TACE） combined with anti-angiogenic drugs for the treatment of unresectable primary liver cancer （PLC）. METHODS Retrieved from Chinese and English databases such as CNKI， the Cochrane Library， Google， and Baidu Academic， randomized controlled trial （RCT） about TACE combined with anti-angiogenic drugs for the treatment of unresectable PLC were collected from the inception to May 27， 2024. After screening the literature， extracting data， and evaluating the quality of the literature， network meta-analysis was performed using R 4.2.2 and Stata 17.0. RESULTS A total of 44 RCT were included， involving 5 607 patients and 8 interventions. The network meta-analysis results showed that for prolonging median overall survival （mOS） and median progression- free survival （mPFS）， TACE+apatinib had the best efficacy， with TACE+apatinib and TACE+sorafenib ranking as the top two. For improving objective response rate （ORR） and disease control rate （DCR）， TACE+donafenib had the best efficacy， with TACE+ donafenib and TACE+ lenvatinib ranking as the top two. In terms of safety， TACE+donafenib was the best， with TACE+donafenib and TACE+apatinib ranking as the top two. CONCLUSIONS TACE+apatinib and TACE+donafenib have good efficacy for patients with unresectable PLC， and TACE+donafenib has the best safety profile.

[Objective]Based on data mining,network pharmacology and molecular docking technology,to explore the rule and mechanism of Chinese medicine in the treatment of chronic viral hepatitis B.[Methods]Clinical research literature on Chinese medicine treatment of chronic viral hepatitis B collected in China National Knowledge Internet(CNKI),Wanfang Database and VIP Database from establishment to September 12,2022,were searched,and the data were standardized and classified.Meanwhile,Excel 2019,Cytoscape 3.8.0 and Qrigin 2021 software were used to analyze the frequency,association rules and systematic clustering of the Chinese medicine compounds meeting the inclusion criteria,and obtain medication rules and core prescriptions.The Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP),Human Gene database(GeneCards)and Online Human Mendelian Inheritance in Man(OMIM)database were used to obtain core prescription active ingredients,therapeutic targets and disease-related targets,respectively.The STRING 11.5 database and Cytoscape 3.8.0 software were used for network visualization,and the Metascape database was used for gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,AutoDock Vina 1.2.3 software were used for molecular docking.[Results]A total of 192 prescriptions were included,including 225 drugs.The drug properties were cold,warm and normal,and the drug flavors were bitter,sweet and acrid,mostly attributed to liver,lung,stomach and spleen channels.The main types of action were deficiency tonic,heat-clearing,diuretic and dehydrating.Association analysis showed that the common compatibility was Atractylodes macrocephala-Curcumae radix-Poria cocos-Salvia miltiorrhiza,Atractylodes macrocephala-Curcumae radix-Poria cocos,Astragalus membranaceus-Phyllanthus urinaria-Salvia miltiorrhiza.The clustering analysis was divided into 4 categories,and the clustering effect was good.Network pharmacology and molecular docking suggested 201 kinds of active ingredients,4 208 targets,2 920 disease targets,104 overlapping targets of drug diseases,and 1 369 biological processes(BP),celluar component(CC)87,molecular function(MF)120 were identified by GO functional enrichment analysis,and KEGG pathway enrichment analysis identified 190 pathways,the conformation of the core components and core target molecular bonding results tended to be stable.[Conclusion]By using literature data mining,network pharmacology and molecular docking technology,the drug use rules and core formulations of traditional Chinese medicine in the treatment of chronic viral hepatitis B were summarized,and the potential therapeutic targets and signaling pathways of the core formulations in the intervention of chronic viral hepatitis B were further explored,and the molecular docking results were good,which could provide ideas and methods for the future research of chronic viral hepatitis B.

Ferroptosis is a kind of programmed cell death, involves multi-molecular and multi-signaling pathways, and the core processes is iron overload and lipid peroxidation. It affects cancer, neurological disease, cardiovascular disease, digestive system disease, and many other diseases. While, ischemia-reperfusion injury is an extremely complex pathological process, including ischemia-reperfusion injury of the heart, brain, liver and kidney, etc., which often occurs in shock, organ surgery and organ transplantation, seriously affecting human health, and there is no effective radical treatment. However, ferroptosis is closely related to ischemia-reperfusion injury so that it is possible to find the prevention and treatment measures of ischemia-reperfusion injury by exploring the internal relationship between them. Therefore, the author tries to summarize the signaling pathways of ferroptosis, and explores the relationship between ferroptosis and ischemia-reperfusion injury of heart, brain, liver and kidney by moderating the ferroptosis targets properly to find the effective ways to treat cancer, improve inflammation and relieve other diseases.