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 explore the changes of hepatic and pancreatic fat content in patients with type 2 diabetes mellitus(T2DM)using quantitative MRI,and to discuss the relationship with pancreatic β-cell function and bone mineral density(BMD).Methods A total of 118 patients with T2DM(T2DM group)were selected as the research subjects.At the same time,100 healthy control(HC)(HC group)who received physical examination were selected.All patients were examined with MRI.Hepatic fat fraction(HFF)and pancreatic fat fraction(PFF)were detected using the iterative decomposition of water and fat with echo asymmetry and least square estimation quantitation(IDEAL-1Q)technology.The homeostasis model assessment of β-cell function(HOMA-β)and homeostasis model assessment of insulin resistance(HOMA-IR)were performed.BMD of L2-L4,femoral neck and total hip were measured by dual-energy X-ray absorptiometry.The correlations among HFF,PFF and HOMA-β,HOMA-IR and BMD of L2-L4,femoral neck and total hip were analyzed by Pearson method.Results HFF and PFF in the T2DM group[(14.12±2.19)％and(8.23±1.60)％]were higher than those in the HC group[(5.30±0.83)％and(4.36±0.85)％],with statistically significant differences(P＜0.05).HOMA-βand BMD of L2-L4,femoral neck and total hip in the T2DM group[14.50±3.63,(0.92±0.13)mg/cm3,(0.77±0.10)mg/cm3 and(0.83±0.12)mg/cm3]were lower than those in the HC group[25.22±5.43,(1.05±0.23)mg/cm3,(0.85±0.18)mg/cm3 and(0.91±0.20)mg/cm3].HOMA-IR in the T2DM group(3.56±1.22)was higher than that in the HC group(1.90±0.45).The differences were statistically significant(P＜0.05).Pearson correlation analysis found that HFF and PFF were negatively correlated with HOMA-β and BMD of L2-L4,femoral neck and total hip,and were positively correlated with HOMA-IR(P＜0.05).Conclusion MRI can be used to quantitatively evaluate hepatic and pancreatic fat content in patients with T2DM.In addition,hepatic and pancreatic fat content are closely related to pancreatic HOMA-β,HOMA-IR and BMD.

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 compare the mid-term clinical effects of AngioJet rheolytic thrombectomy assisted catheter-directed thrombolysis (ART+CDT) with catheter-directed thrombolysis (CDT) in the treatment of acute deep venous thrombosis of lower extremities.Methods:Ninety-one patients admitted to the Department from Jan 2016 to Dec 2017 were placed with inferior vena cava filters and divided into ART+CDT group (30 cases)and CDT group (61 cases). Total urokinase dosge, thrombolytic time, operative cost, length of hospital stay, detumescence rate, thrombus clearance rate, cumulative patency rate of lower limb veins, Villalta score at 2 years and 5 years, thrombosis recurrence rate and chronic venous insufficiency quality of life questionnaire were compared between the two groups.Results:The success rate of surgery was 100% in both groups, there was no mortality. There were significant differences in the short-term postoperative outcomes between the two groups in terms of total dosage of urokinase, thrombolysis time, total cost of surgery, length of hospital stay, detumescence rate, venous patency scores before and after treatment, and venous patency rate (all P<0.05). For the mid- and long-term postoperative outcomes of 2 and 5 years, there were no significant differences in the incidence of PTS, recurrence rate of thrombus, chronic venous function scale, and cumulative patency rate at 2 years (all P>0.05). Conclusions:ART+CDT has a significant advantage over CDT alone in terms of early efficacy and early reopening of blood flow in patients. Both ART+CDT and CDT have a low incidence of PTS and a low recurrence rate of thrombus in the mid-term follow-up, and both have satisfactory performance in the mid- and long-term efficacy of interventional treatment of deep venous thrombosis of lower limbs.

In the field of biomedicine,two-dimensional(2D)cell lines and animal models have played an im-portant role in the study of cell pathways and drug targets.However,due to species differences between humans and other animals,and the lack of hierarchy,cellular diversity,and cell-cell or cell-matrix interactions,2D cell lines could not ful-ly reflect what cells actually look like in the human body.Organoids are three-dimensional(3D)in vitro culture models de-rived from autologous tissue stem cells,which make up for the defects of 2D culture and can simulate the structure and function of real human organs to a certain extent,providing new ideas for disease diagnosis and treatment.Among them,lung organoids(LO)are a typical case studying the development process of human lung and the generation principle of lung diseases.Relevant studies have provided help for the treatment of pulmonary fibrosis,lung cancer,lung injury and other diseases.This paper aims to summarize and analyze the research progress of lung organoids in recent years,and fur-ther summarize the application of LO in the diagnosis and treatment of lung diseases.

Objective:To conduct a systematic evaluation of prognostic factors for retreatment of esophageal cancer patients with locoregional recurrence after radical chemoradiotherapy, and provide a clinical reference for selecting individualized retreatment schemes and improving their survival.Methods:A retrospective analysis was performed on the clinical data of 85 patients with esophageal cancer who experienced locoregional recurrence at least 1 year after radical radiotherapy or chemotherapy at the Department of Radiation Oncology in the Fourth Hospital of Hebei Medical University from January 2008 to December 2017. The effects of different nutritional and immune status and retreatment schemes on survival were compared, and the prognostic factors for retreatment were subjected to comprehensive subgroup analysis.Results:As of December 2021, the follow-up rate for all patients was 93%. The 1-, 2-, 3-, and 5-year overall survival rates of all patients after retreatment were 31.5%, 18.6%, 10.6%, and 6.6%, respectively. For patients who received radiotherapy or chemoradiotherapy, the 1-, 2-, 3-, and 5-year overall survival rates were 36.8%, 22.3%, 13.0% and 9.3%, respectively. Multivariable analysis showed that the time interval between the first treatment and recurrence, the retreatment schemes after recurrence, the level of serum albumin before retreatment, and the prognostic nutritional index before retreatment were independent prognostic factors for survival after retreatment ( P<0.05). Subgroup analysis was performed on the combinations of peripheral blood hemoglobin level, albumin level, and prognostic nutritional index before retreatment, as well as systemic immune inflammation index and short-term curative effect after retreatment. The results showed that the comprehensive analysis of blood routine and serum albumin indicators could accurately predict the survival after retreatment. Conclusions:The nutritional and immune status of patients with locoregional recurrence of esophageal cancer after chemoradiotherapy can be used to predict the prognosis of retreatment. The time interval between the first treatment and recurrence and the retreatment scheme significantly affect the survival after retreatment. The retreatment scheme should be rigorously evaluated and appropriately selected to improve the benefit-risk ratio.

Fear memory contextualization is critical for selecting adaptive behavior to survive. Contextual fear conditioning (CFC) is a classical model for elucidating related underlying neuronal circuits. The primary visual cortex (V1) is the primary cortical region for contextual visual inputs, but its role in CFC is poorly understood. Here, our experiments demonstrated that bilateral inactivation of V1 in mice impaired CFC retrieval, and both CFC learning and extinction increased the turnover rate of axonal boutons in V1. The frequency of neuronal Ca²⁺ activity decreased after CFC learning, while CFC extinction reversed the decrease and raised it to the naïve level. Contrary to control mice, the frequency of neuronal Ca²⁺ activity increased after CFC learning in microglia-depleted mice and was maintained after CFC extinction, indicating that microglial depletion alters CFC learning and the frequency response pattern of extinction-induced Ca²⁺ activity. These findings reveal a critical role of microglia in neocortical information processing in V1, and suggest potential approaches for cellular-based manipulation of acquired fear memory.
Mice ; Animals ; Primary Visual Cortex ; Extinction, Psychological/physiology* ; Learning/physiology* ; Fear/physiology* ; Hippocampus/physiology*

Objective:To study the inactivation effects of microwave on human adenovirus 2 (HAdV-2) in simulated infectied wastes, and to explore its molecular mechanism.Methods:25 μl of HAdV-2 virus suspension was dripped with medical disposable gloves, masks and cotton swabs to simulate infectied wastes, and irradiated under different microwave conditions: gloves and masks were irradiated for 30 s, 60 s, and 90 s at 300 W, 500 W, and 700 W, respectively. Cotton swabs irradiate 60 s, 90 s, 120 s at 500 W and 700 W respectively. Temperature changes were recorded, and the inactivation logarithmic values were calculated by the 50% endpoint method to evaluate the microwave inactivation effects, and the proliferation ability of the virus was detected by qPCR. The damage of Penton, Fiber, Hexon and E2 B genes was detected by PCR. The virus was treated with the highest temperature of 76 ℃ during microwave irradiation to study whether there was non-thermal effect during microwave disinfection. Results:After microwave irradiation of infectied waste, the temperature of masks and gloves carriers rises rapidly, with the highest temperature of 76 ℃. The temperature of the cotton swab carriers rose slowly, and the highest temperature is 65 ℃. The inactivation effect of microwave on HAdV-2 was positively correlated with microwave power and irradiation time. In the mask and glove group, microwave power of 700 W irradiated for 60 seconds, and the inactivation logarithm value could reach 3.0, In the cotton swab group, microwave power of 700 W irradiated for 120 seconds, and the inactivation logarithm value was still less than 3.0. This indicated that there were differences in the conditions for microwave inactivation of the virus in different carriers. The qPCR result showed that microwave irradiation could weak the proliferation ability of the virus. Microwave irradiation had no effect on the virus's Penton and Fiber genes, but caused some damage to the Hexon and E2 B genes. The inactivation effect of individual heat treatment on HAdV-2 was weaker than that of microwave irradiation, and there was no damage to the Hexon, Penton, Fiber, and E2 B genes. This indicated the presence of non thermal effects during the microwave inactivation process. Conclusions:Microwave irradiation can inactivate HAdV-2 in simulated infectied wastes through thermal and non-thermal effects, and its damage to viral DNA is one of the mechanisms of virus inactivation.

Objective:To conduct a visual analysis of the literature on burn-related coagulation dysfunction and to explore the current research status, evolution process, hot topics, and future research trends in burn-related coagulation dysfunction at home and abroad.Methods:The bibliometrics method was used. The literature on burn-related coagulation dysfunction which were published in Web of Science and China National Knowledge Internet databases from January 1, 1950 to May 1, 2022, and met the inclusion criteria were retrieved for publication volume analysis. The literature on burn-related coagulation dysfunction were retrieved as above in the core collection of Web of Science and China National Knowledge Internet databases, and CiteSpace 5.8.R3 software was used to perform co-occurrence analysis, cluster analysis, and literature co-citation analysis of key words. Results:A total of 501 and 235 literature on burn-related coagulation dysfunction were retrieved from Web of Science database and China National Knowledge Internet database, respectively. The literature on burn-related coagulation dysfunction emerged from 1975 and 1950, respectively, in China and abroad, which were gradually increased later. The frequency and centrality of Chinese key words such as 烧伤, 凝血功能, 血小板 were high in 235 literature in China National Knowledge Internet database, and the frequency and centrality of key words such as burn, coagulation, and deep vein thrombosis were high in 340 literature in the core collection of Web of Science database. In China National Knowledge Internet database, the top 6 Chinese key words in terms of burst intensity were 烧伤患者, 临床意义, 烧伤面积, 凝血功能, 预后, 血小板, and the first 3 among which were burst key words in the early stage; and in the core collection of Web of Science database, the key words with higher burst intensity were disseminated intravascular coagulation and pulmonary embolism, which were the burst key words in the early stage. The representative clustering labels in China National Knowledge Internet database were #0 烧伤, #1 休克, and #2 并发症, etc., and the representative clustering labels in the core collection of Web of Science database were #0 risk, #1 surgical patient, and #2 sepsis. Early researches in China National Knowledge Internet database and the core collection of Web of Science database focused on the presence of burn-related coagulation dysfunction itself, while the late researches focused on the relationship between burn-related coagulation dysfunction and inflammation, immunity, coagulation in general, and wounds. From 2010 onwards, there were a large number of core cited literature in the core collection of Web of Science database, and the prevention and treatment of vein thromboembolism was the most popular research direction in recent years. The researches on optimization and standardization of diagnostic methods and the overall mechanism of burn-related coagulation dysfunction would be the main research directions in the future. Conclusions:The research hotspots and evolution processes of burn-related coagulation dysfunction at home and abroad have both similarities and differences, and the current research hotspot is the relationship between coagulation and inflammation, immunity. With researches increasingly deepening, the researches on optimization and standardization of diagnostic methods and the overall mechanism of burn-related coagulation dysfunction will be the main research directions in the future.