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BACKGROUND: One of the main illnesses in the globe that causes impairment and death in people is stroke. In the globe today, it ranks as the second leading cause of death and the leading cause of death in China. OBJECTIVE: This paper analyses into the critical role of risk perception in developing individual awareness of stroke risk and encouraging proactive preventive health behaviors, essential for effective primary stroke prevention strategies and reduced stroke incidence. It discusses the concept of risk perception, the content and dimensions of global stroke assessment tools, and their application status, aiming to provide insights for their development and intervention research. METHODS: Risk perception encompasses subjective assessments of stroke likelihood and severity, influenced by personal experiences, knowledge of risk factors, beliefs about prevention effectiveness, and emotional responses. Global stroke assessment tools, like the Framingham Stroke Risk Score and CHA2DS2-VASc Score, evaluate stroke risk based on factors such as age, gender, blood pressure, and cholesterol levels. In order to improve risk perception and proactive health management and lower the burden of strokes, the paper assesses the advantages and disadvantages of these tools and makes recommendations for improving accessibility, customizing interventions, running educational campaigns, promoting multidisciplinary collaboration, and integrating technology. RESULTS: By combining the research tools of stroke risk perception, it is found that the evaluation tools are mostly single-dimensional evaluation tools centered on the two dimensions of onset possibility and susceptibility. CONCLUSION: Some scholars have developed multi-dimensional evaluation tools, but the evaluation population is relatively limited, and the evaluation system lacks comprehensiveness and systematization.
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BACKGROUND: Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) plays a crucial role in metabolizing and detoxifying endogenous and exogenous substances. However, its contribution to the progression of liver damage remains unclear. AIM: To determine the role and mechanism of UGT1A1 in liver damage progression. METHODS: We investigated the relationship between UGT1A1 expression and liver injury through clinical research. Additionally, the impact and mechanism of UGT1A1 on the progression of liver injury was analyzed through a mouse model study. RESULTS: Patients with UGT1A1 gene mutations showed varying degrees of liver damage, while patients with acute-on-chronic liver failure (ACLF) exhibited relatively reduced levels of UGT1A1 protein in the liver as compared to patients with chronic hepatitis. This suggests that low UGT1A1 levels may be associated with the progression of liver damage. In mouse models of liver injury induced by carbon tetrachloride (CCl4) and concanavalin A (ConA), the hepatic levels of UGT1A1 protein were found to be increased. In mice with lipopolysaccharide or liver steatosis-mediated liver-injury progression, the hepatic protein levels of UGT1A1 were decreased, which is consistent with the observations in patients with ACLF. UGT1A1 knockout exacerbated CCl4- and ConA-induced liver injury, hepatocyte apoptosis and necroptosis in mice, intensified hepatocyte endoplasmic reticulum (ER) stress and oxidative stress, and disrupted lipid metabolism. CONCLUSION: UGT1A1 is upregulated as a compensatory response during liver injury, and interference with this upregulation process may worsen liver injury. UGT1A1 reduces ER stress, oxidative stress, and lipid metabolism disorder, thereby mitigating hepatocyte apoptosis and necroptosis.
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Glucuronosiltransferase , Fígado , Animais , Humanos , Camundongos , Modelos Animais de Doenças , Glucuronosiltransferase/genética , Glucuronosiltransferase/metabolismo , Fígado/metabolismoRESUMO
BACKGROUND: Genetic factors of chronic intestinal ulcers are increasingly garnering attention. We present a case of chronic intestinal ulcers and bleeding associated with mutations of the activin A receptor type II-like 1 (ACVRL1) and phospholipase A2 group IVA (PLA2G4A) genes and review the available relevant literature. CASE SUMMARY: A 20-year-old man was admitted to our center with a 6-year history of recurrent abdominal pain, diarrhea, and dark stools. At the onset 6 years ago, the patient had received treatment at a local hospital for abdominal pain persisting for 7 d, under the diagnosis of diffuse peritonitis, acute gangrenous appendicitis with perforation, adhesive intestinal obstruction, and pelvic abscess. The surgical treatment included exploratory laparotomy, appendectomy, intestinal adhesiolysis, and pelvic abscess removal. The patient's condition improved and he was discharged. However, the recurrent episodes of abdominal pain and passage of black stools started again one year after discharge. On the basis of these features and results of subsequent colonoscopy, the clinical diagnosis was established as inflammatory bowel disease (IBD). Accordingly, aminosalicylic acid, immunotherapy, and related symptomatic treatment were administered, but the symptoms of the patient did not improve significantly. Further investigations revealed mutations in the ACVRL1 and PLA2G4A genes. ACVRL1 and PLA2G4A are involved in angiogenesis and coagulation, respectively. This suggests that the chronic intestinal ulcers and bleeding in this case may be linked to mutations in the ACVRL1 and PLA2G4A genes. Oral Kangfuxin liquid was administered to promote healing of the intestinal mucosa and effectively manage clinical symptoms. CONCLUSION: Mutations in the ACVRL1 and PLA2G4A genes may be one of the causes of chronic intestinal ulcers and bleeding in IBD. Orally administered Kangfuxin liquid may have therapeutic potential.
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BACKGROUND: Patients with obstructive jaundice caused by intrahepatic bile duct stones can be effectively managed by surgery. However, some patients may develop postoperative complications, liver failure, and other life-threatening situations. Here, we report a patient with mutations in the uridine 5'-diphospho-glucuronosyltransferase 1A1 (UGT1A1) and bile salt export pump (adenosine triphosphate-binding cassette subfamily B member 11, ABCB11) genes who presented multiple intrahepatic bile duct stones and cholestasis, and the jaundice of the patient increased after partial hepatectomy. CASE SUMMARY: A 52-year-old male patient admitted to the hospital on October 23, 2021, with a progressive exacerbation of jaundice, was found to have multiple intrahepatic bile duct stones with the diagnoses of obstructive jaundice and acute cholecystitis. Subsequently, the patient underwent left hepatectomy with biliary exploration, stone extraction, T-tube drainage, and cholecystectomy without developing any intraoperative complications. The patient had a dark urine color with worsening jaundice postoperatively and did not respond well to plasma exchange and other symptomatic and supportive treatments. Since the progressive increase in postoperative bilirubin could not be clinically explained with any potential reason, including, if not at all, viral infection, cholangitis, autoimmune liver disease, and other causes, the patient underwent whole-exon screening for any genetic diseases, which surprisingly identified UGT1A1 and ABCB11 gene mutations related to glucuronidation of indirect bilirubin as well as bile acid transport in hepatocytes, respectively. Thus, we hypothesized that postoperative refractory cholestasis might result from UGT1A1 and ABCB11 gene mutations and further recommended liver transplantation to the patient, who eventually declined it and died from liver failure six months later. CONCLUSION: Surgery may aggravate cholestasis in patients with multiple intrahepatic bile duct stones and cholestasis associated with UGT1A1 and ABCB11 gene mutations. A liver transplant may be the best option if active medical treatment fails.
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BACKGROUND: Endoplasmic reticulum (ER) stress contributes to the pathogenesis of chronic liver diseases, but how hepatocytes respond to ER stress has not been clarified. Alpha-fetoprotein (AFP) is secreted by hepatoma cells and elevated levels of serum AFP are associated with development of liver malignancies. AIM: To investigate whether and how AFP could regulate ER stress and hepatocyte injury. METHODS: The distribution of AFP and the degrees of ER stress in liver tissues and liver injury were characterized by histology, immunohistochemistry, and Western blot in biopsied human liver specimens, two mouse models of liver injury and a cellular model. The levels of AFP in sera and the supernatants of cultured cells were quantified by chemiluminescence. RESULTS: High levels of intracellular AFP were detected in liver tissues, particularly in the necrotic areas, from patients with chronic liver diseases and mice after carbon tetrachloride (CCl4) administration or induction of ER stress, but not from the controls. The induced intracellular AFP was accompanied by elevated activating transcription factor-6 (ATF6) expression and protein kinase R-like ER kinase (PERK) phosphorylation in mouse livers. ER stress induced AFP expression in LO2 cells and decreased their viability. ATF6, but not PERK, silencing mitigated the ER-stress-induced AFP expression in LO2 cells. Conversely, AFP silencing deteriorated the ER stress-mediated LO2 cell injury and CCl4 administration-induced liver damages by increasing levels of cleaved caspase-3, the C/enhancer binding protein homologous protein expression, mixed lineage kinase domain-like pseudokinase and PERK phosphorylation, but decreasing ATF6 expression. CONCLUSION: ER stress upregulated intra-hepatocyte AFP expression by activating ATF6 during the process of liver injury and intracellular AFP attenuated hepatocyte apoptosis and necroptosis by alleviating ER stress.
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Estresse do Retículo Endoplasmático , Hepatopatias , Animais , Apoptose , Hepatócitos/patologia , Humanos , Hepatopatias/patologia , Camundongos , Necroptose , alfa-Fetoproteínas/metabolismoRESUMO
BACKGROUND: Soil salinization is a threat to food security. China is rich in saline land resources for potential and current utilization. The cultivation and promotion of salt-tolerant rice varieties can greatly improve the utilization of this saline land. The super hybrid rice Chaoyouqianhao (CY1000) is one of the most salt-tolerant rice varieties and is widely used, but the molecular mechanism underlying its salt tolerance is not clear. RESULTS: In this study, the characteristics of CY1000 and its parents were evaluated in the field and laboratory. The results showed that aboveground parts of CY1000 were barely influenced by salt stress, while the roots were less affected than those of its parents. A comparative transcriptomic strategy was used to analyze the differences in the response to salt stress among the male and female parents of CY1000 at the seedling stage and the model indica rice 93-11. We found that the salt tolerance of CY1000 was mainly inherited from its male parent R900, and its female parent GX24S showed hardly any salt tolerance. To adapt to salt stress, CY1000 and R900 upregulated the expression of genes associated with soluble component synthesis and cell wall synthesis and other related genes and downregulated the expression of most genes related to growth material acquisition and consumption. In CY1000 and R900, the expression of genes encoding some novel key proteins in the ubiquitination pathway was significantly upregulated. After treatment with MG-132, the salt tolerance of CY1000 and R900 was significantly decreased and was almost the same as that of the wild type after salt stress treatment, indicating that ubiquitination played an important role in the salt tolerance mechanism of CY1000. At the same time, we found that some transcription factors were also involved in the salt stress response, with some transcription factors responding only in hybrid CY1000, suggesting that salt tolerance heterosis might be regulated by transcription factors in rice. CONCLUSION: Our results revealed that the ubiquitination pathway is important for salt tolerance in rice, and several novel candidate genes were identified to reveal a novel salt tolerance regulation network. Additionally, our work will help clarify the mechanism of heterosis in rice. Further exploration of the molecular mechanism underlying the salt tolerance of CY1000 can provide a theoretical basis for breeding new salt-tolerant rice varieties.
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Oryza , Regulação da Expressão Gênica de Plantas , Oryza/metabolismo , Melhoramento Vegetal , Estresse Salino , Fatores de Transcrição/genética , TranscriptomaRESUMO
OBJECTIVE: To evaluate the effect and safety of transurethral prostatectomy with the bipolar plasmakinetic technique (PKRP) compared with the transurethral resection (TURP) in the treatment of benign prostate hyperplasia (BPH). METHOD: Four hundred BPH patients with matched lesions were divided into 2 groups: 200 patients, aged 74.1 (58-91), underwent transurethral prostatectomy with PKRP, and 200 patients, aged 73.8 (56-90), underwent TURP. RESULT: In the PKRP group the average IPSS decreased from 27.1 +/- 4.5 preoperatively to 11.3 +/- 3.4 postoperatively 6 months after (P < 0.01), the. average maximum flow-rate Q (max) increased from 6.1 +/- 2.4 ml/s preoperatively to 18.6 +/- 3.5 ml/s postoperatively (P < 0.01), and the average residual urine (RU) reduced from 102.3 +/- 43.3 ml preoperatively to 22.6 +/- 16.3 ml after the operation (P < 0.01). However in the TURP group the average IPSS decreased from 26.9 +/- 4.2 preoperatively to 10.8 +/- 3.6 6 months after the operation (P < 0.01), the Q (max) increased from 5.7 +/- 2.4 ml/s preoperatively to 19.1 +/- 3.7 ml/s postoperatively (P < 0.01), and the average RU decreased from 102.3 +/- 43.3 ml preoperatively to 22.6 +/- 16.3 ml after the operation (P < 0.01). There were no significant differences in these parameters between these 2 groups (all P > 0.05). The average catheter retention time was 31.5 h in the PKRP, significantly shorter than that in the TURP group (61.5 hours, P < 0.01). The incidence rate of post-operational asynodia in the PKRP group was 14.3%, not significantly different from that in the TURP group (15.2%, P > 0.05). During the operation no hemorrhage or transurethral resection syndrome (TURS) occurred in the PKRP group, however, there were 5 cases of TURS and 18 cases of blood transfusion in the TURP group. CONCLUSION: PKRP has the same therapeutic efficacy as TURP on BPH. Moreover, it was more cheaper and with lower complication than TURP.