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Objective:To explore the independent risk factors of portal vein thrombosis (PVT) in liver cirrhosis, and to establish and evaluate a risk prediction model for PVT in patients with cirrhosis.Methods:A total of 295 cases of cirrhosis hospitalized in Renmin Hospital of Wuhan University from December 2019 to October 2021 were divided into a modeling set ( n=207) and an internal validation set ( n=88) by the random number table. In addition, patients with cirrhosis hospitalized in Yichang Central People's Hospital, Wuhan Puren Hospital, No.2 People's Hospital of Fuyang City and People's Hospital of China Three Gorges University during the same period were collected as an external validation set ( n=92). The modeling set was divided into PVT group ( n=56) and non-PVT group ( n=151). Univariate analysis was used to preliminarily screen the related indicators of PVT, and then multivariate logistic regression analysis with forward stepwise regression was used to determine independent risk factors for PVT. A nomogram prediction model was constructed based on the independent risk factors obtained. The internal and external validation set were used to verify the predictive ability of the model. Distinction degree was used to evaluate the ability of the model to distinguish patients with or without PVT. Hosmer-Lemeshow goodness-of-fit test was used to evaluate the consistency between predicted risk and the actual risk of the model. Results:Univariate analysis showed that smoking, history of splenectomy, trans-jugular intrahepatic portosystemic shunt (TIPS), gastrointestinal bleeding and endoscopic variceal treatment, and levels of hemoglobin, alanine aminotransferase, aspartate aminotransferase and D-dimer were significantly different between the PVT group and the non-PVT group ( P<0.05). Multivariate logistic regression analysis found that smoking ( P=0.020, OR=31.21, 95% CI: 1.71-569.40), levels of D-dimer ( P=0.003, OR=1.12, 95% CI: 1.04-1.20) and hemoglobin ( P=0.039, OR=0.99, 95% CI: 0.97-1.00), history of TIPS ( P=0.011, OR=18.04, 95% CI: 1.92-169.90) and endoscopic variceal treatment ( P=0.001, OR=3.21, 95% CI: 1.59-6.50) were independent risk factors for PVT in patients with liver cirrhosis. Receiver operator characteristic (ROC) curve analysis showed that the area under the ROC curve (AUC) for the internal validation set was 0.802 (95% CI: 0.709-0.895) ( P<0.001), and the AUC for the external validation set was 0.811 (95% CI: 0.722-0.900) ( P<0.001). Both AUC were larger than 0.75. The calibration curve of Hosmer-Lemeshow goodness-of-fit test showed that the P values of both internal validation set ( χ2=3.602, P=0.891) and the external validation set ( χ2=11.025, P=0.200) were larger than 0.05. Conclusion:Smoking, history of TIPS or endoscopic variceal treatment, levels of D-dimer and hemoglobin are independent risk factors for PVT in patients with liver cirrhosis. The prediction nomogram model based on the above factors has strong predictive ability.
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Remdesivir (RDV) is the only US Food and Drug Administration (FDA)-approved drug for treating COVID-19. However, RDV can only be given by intravenous route, and there is a pressing medical need for oral antivirals. Significant evidence suggests that the role of the parent nucleoside GS-441524 in the clinical outcomes of RDV could be largely underestimated. We performed an
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Of all known small molecules targeting human immunodeficiency virus (HIV) capsid protein (CA), PF74 represents by far the best characterized chemotype, due to its ability to confer antiviral phenotypes in both early and late phases of viral replication. However, the prohibitively low metabolic stability renders PF74 a poor antiviral lead. We report herein our medicinal chemistry efforts toward identifying novel and metabolically stable small molecules targeting the PF74 binding site. Specifically, we replaced the inter-domain-interacting, electron-rich indole ring of PF74 with less electron-rich isosteres, including imidazolidine-2,4-dione, pyrimidine-2,4-dione, and benzamide, and identified four potent antiviral compounds (
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Objective To investigate the clinical efficacy of endoscopic submucosal dissection (ESD)for the treatment of colorectal tumors, and to analyze risk factors affecting operation time. Methods A retrospective study was conducted using data of 74 cases with colorectal tumor,who underwent ESD in Department of Gastroenterology of Wuhan University Renmin Hospital from January 2014 to September 2015. The clinical efficacy of ESD, occurrence of complications and follow-up results were summarized,and the risk factors of operation time were analyzed. Results The rate of ESD en bloc resection and histological complete resection was 97.30%(72/74)and 89.19%(66/74), respectively. Among the 8 cases of histological non-curative resection, 2 cases received appended surgical procedures because of deep invasion of tumor(SM2),6 cases were given close follow-up according to the pathological result of adenomas. Among the 74 cases, no acute hemorrhage or pneumoperitoneum occurred. Four cases (5.41%, 4/74)had postoperative delayed bleeding, and were successfully treated by endoscopic hemostasis. Four cases(5.41%, 4/74)had intraoperative perforation, and were successfully treated by endoscope. No recurrence or abnormal lesions occurred during the follow-up of 15-35 months. Multivariate linear regression analysis showed that tumor size was a main risk factor for ESD operation time(P=0.000). Conclusion ESD, as a minimally invasive treatment, is safe and effective for the treatment of colorectal tumors,and the tumor size is a main risk factor of ESD operation time.
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Objective To investigate the effects of nuciferine on hyperlipidemia in mice and to clarify the molecular mechanism. Methods Mice were divided into three groups according to the diet: normal control group ( n=10 ) , model control group (n=10), and the intervention group (n=10). The normal control group was treated with common diet (ANI-76A feed:12. 4% fat, 68. 8% carbohydrate, 18. 8% protein). The model control group was induced with high fat diet (37. 1% fat, 42. 4% carbohydrate, 20. 5% protein). The intervention group was supplemented with 0. 5% nuciferine based on high fat diet. The mice were allowed free access to food and water for a total of 10 weeks. Several indices were analyzed in the 3 groups, including the body weight, serum lipid, lipid metabolism key enzyme, oxidative stress and metabolic pathway. Results Our results suggested that the high-fat diet-induced animal models developed obesity and dyslipidemia (P0.05).Theactivityofhepaticlipidmetabolismkeyenzymes[(4.15±1.26) U·mL-1vs.(9.01±1.34) U·mL-1] andthe activity of hepatic lipase and lipoprotein lipase[(8.12±3.07) U·mL-1 vs.(13.48±3.75) U·mL-1] were elevated.Oxidative stress was also affected by nuciferine (P<0. 05). Mechanism study suggested that lipid synthesis genes (like SREBP-1c, FAS, SCD-1 and PPAR gamma mRNA) were up-regulated by high fat diet (P<0. 05), and the lipid oxidation metabolism genes, PPARαand CPT-1a mRNA, were down-regulated (P<0. 05), while the intervention group treatment reversed these changes (P<0. 05). Conclusion Nuciferine can improve hyperlipidemia, which might be related to the regulation of enzyme activity, oxidative stress and the changes of lipid synthesis and oxidative metabolism.
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OBJECTIVE To study the distribution of pathogens and their antibiotic resistance in systemic lupus erythematosus(SLE)patients with gram-negative bacterial infections,for guiding the rational use of antibiotics therapy.METHODS The identification was analyzed by ATB Expression automatic microbiology analytical instrument system.The bacterial susceptibility test was done by Kirby-Bauer agar diffusion method.RESULTS Among 346 patients included,112(32.4%)had bacterial infections.A total of 181 pathogens strains had been isolated.Among 181 isolates,Escherichia coli,Pseudomonas aeruginosa,Klebsiella pneumoniae,Acinetobacter baumannii,Proteus mirabilis,and Enterobacter cloacae were the main pathogens.The ESBLs producing rates in E.coli and K.pneumoniae were 27.5% and 28.1%.Piperacillin/tazobactam and cefepime had less activity against A.baumannii and low resistant to other Gram-negative bacilli(0-46.2% and 13.0-33.3%).Meropenem,imipenem and cefoperazone/sulbactam showed greater activity against Gram-negative bacilli,their resistant rates were 0-17.1%,0-22.9% and 0-38.5%,respectively.CONCLUSIONS The clinical features of SLE patients with bacterial infections are lack of specificity.The data will be useful for reasonably choosing antimicrobial agents in the treatment of SLE patients with bacterial infections.